Patent application title: COMPOSITIONS AND METHODS FOR TREATING LEBER'S HEREDITARY OPTIC NEUROPATHY WITH NADH DEHYDROGENASE PROTEINS
Inventors:
Bin Li (Wuhan, CN)
IPC8 Class: AA61K4800FI
USPC Class:
1 1
Class name:
Publication date: 2022-09-01
Patent application number: 20220273816
Abstract:
Disclosed herein is a recombinant nucleic acid, comprising: a
mitochondrial targeting sequence; a mitochondrial protein coding
sequence, wherein said mitochondrial protein coding sequence encodes a
polypeptide comprising a mitochondrial protein; and a 3'UTR nucleic acid
sequence. Also disclosed is a pharmaceutical composition comprising the
recombinant nucleic acid and a method of treating Leber's hereditary
optic neuropathy (LHON) using the pharmaceutical composition.Claims:
1. A recombinant nucleic acid, comprising: a mitochondrial targeting
sequence; a mitochondrial protein coding sequence comprising a sequence
that is at least 99% identical to SEQ ID NO: 11 or 12; and a 3'UTR
nucleic acid sequence.
2. The recombinant nucleic acid of claim 1, wherein said mitochondrial targeting sequence encodes a polypeptide comprising a peptide sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 129-159.
3. The recombinant nucleic acid of claim 1, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 2.
4. The recombinant nucleic acid of claim 1, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 3.
5. The recombinant nucleic acid of claim 1, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 4.
6. The recombinant nucleic acid of claim 1, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 5.
7. The recombinant nucleic acid of claim 1, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 1.
8. The recombinant nucleic acid of claim 1, wherein said mitochondrial protein coding sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 12.
9. The recombinant nucleic acid of any one of claims 1-8, wherein said 3'UTR nucleic acid sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 111-125.
10. The recombinant nucleic acid of any one of claims 1-8, wherein said 3'UTR nucleic acid sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 13 or SEQ ID NO: 14.
11. The recombinant nucleic acid of claim 1, wherein said recombinant nucleic acid comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 25-28, 39-42, 53-56, 67-70, and 81-84.
12. A recombinant nucleic acid, comprising: a mitochondrial targeting sequence; a mitochondrial protein coding sequence comprising a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to SEQ ID NO: 11 or 12; and a 3'UTR nucleic acid sequence.
13. The recombinant nucleic acid of claim 12, wherein said mitochondrial targeting sequence comprises a sequence encodes a polypeptide selected from the group consisting of hsCOX10, hsCOX8, scRPM2, IcSirt5, tbNDUS7, ncQCR2, hsATP5G2, hsLACTB, spilv1, gmCOX2, crATP6, hsOPA1, hsSDHD, hsADCK3, osP0644B06.24-2, Neurospora crassa ATP9 (ncATP9), hsGHITM, hsNDUFAB1, hsATP5G3, crATP6_hsADCK3, ncATP9_ncATP9, zmLOC100282174, ncATP9_zmLOC100282174_spilv1_ncATP9, zmLOC100282174_hsADCK3_crATP6_hsATP5G3, zmLOC100282174_hsADCK3_hsATP5G3, ncATP9_zmLOC100282174, hsADCK3_zmLOC100282174_crATP6_hsATP5G3, crATP6_hsADCK3_zmLOC100282174_hsATP5G3, hsADCK3_zmLOC100282174, hsADCK3_zmLOC100282174_crATP6, ncATP9_zmLOC100282174_spilv1_GNFP_ncATP9, and ncATP9_zmLOC100282174_spilv1IcSirt5_osP06441306.24-2_hsATP5G2_ncATP9.
14. The recombinant nucleic acid of claim 12 or 13, wherein said mitochondrial targeting sequence encodes a polypeptide comprising a peptide sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 129-159.
15. The recombinant nucleic acid of any one of claims 12-14, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 2 or 3.
16. The recombinant nucleic acid of any one of claims 12-14, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 4.
17. The recombinant nucleic acid of any one of claims 12-14, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 5.
18. The recombinant nucleic acid of any one of claims 12-14, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 1.
19. The recombinant nucleic acid of any one of claims 12-18, wherein said 3'UTR nucleic acid sequence is located at 3' of said mitochondrial targeting sequence.
20. The recombinant nucleic acid of any one of claims 12-19, wherein said 3'UTR nucleic acid sequence comprises a sequence selected from the group consisting of hsACO2, hsATP5B, hsAK2, hsALDH2, hsCOX10, hsUQCRFS1, hsNDUFV1, hsNDUFV2, hsSOD2, hsCOX6c, hsIRP1, hsMRPS12, hsATP5J2, rnSOD2, and hsOXA1L.
21. The recombinant nucleic acid of any one of claims 12-20, wherein said 3'UTR nucleic acid sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 111-125.
22. The recombinant nucleic acid of any one of claims 12-21, wherein said 3'UTR nucleic acid sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 13 or SEQ ID NO: 14.
23. The recombinant nucleic acid of any one of claims 12-22, wherein said mitochondrial targeting sequence is located at 5' of said 3'UTR nucleic acid sequence.
24. The recombinant nucleic acid of any one of claims 12-22, wherein said mitochondrial targeting sequence is located at 3' of said mitochondrial targeting sequence.
25. The recombinant nucleic acid of any one of claims 12-24, wherein said recombinant nucleic acid comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 25-28, 39-42, 53-56, 67-70, and 81-84.
26. The recombinant nucleic acid of any one of claims 12-25, wherein said mitochondrial protein coding sequence encodes a mitochondrial protein comprising or consisting of a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 162.
27. A recombinant nucleic acid, comprising a mitochondrial protein coding sequence, wherein said mitochondrial protein coding sequence encodes a polypeptide comprising a mitochondrial protein, wherein said mitochondrial protein coding sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to SEQ ID NO: 11 or 12.
28. The recombinant nucleic acid of claim 27, further comprising a mitochondrial targeting sequence.
29. The recombinant nucleic acid of claim 27 or 28, wherein said mitochondrial targeting sequence comprises a sequence encodes a polypeptide selected from the group consisting of hsCOX10, hsCOX8, scRPM2, IcSirt5, tbNDUS7, ncQCR2, hsATP5G2, hsLACTB, spilv1, gmCOX2, crATP6, hsOPA1, hsSDHD, hsADCK3, osP0644B06.24-2, Neurospora crassa ATP9 (ncATP9), hsGHITM, hsNDUFAB1, hsATP5G3, crATP6_hsADCK3, ncATP9_ncATP9, zmLOC100282174, ncATP9_zmLOC100282174_spilv1_ncATP9, zmLOC100282174_hsADCK3_crATP6_hsATP5G3, zmLOC100282174_hsADCK3_hsATP5G3, ncATP9_zmLOC100282174, hsADCK3_zmLOC100282174_crATP6_hsATP5G3, crATP6_hsADCK3_zmLOC100282174_hsATP5G3, hsADCK3_zmLOC100282174, hsADCK3_zmLOC100282174_crATP6, ncATP9_zmLOC100282174_spilv1_GNFP_ncATP9, and ncATP9_zmLOC100282174_spilv1IcSirt5_osP06441306.24-2_hsATP5G2_ncATP9.
30. The recombinant nucleic acid of any one of claims 27-29, wherein said mitochondrial targeting sequence encodes a polypeptide comprising a peptide sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 129-159.
31. The recombinant nucleic acid of any one of claims 27-30, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 2.
32. The recombinant nucleic acid of any one of claims 27-31, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 3.
33. The recombinant nucleic acid of any one of claims 27-32, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 4.
34. The recombinant nucleic acid of any one of claims 27-33, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 5.
35. The recombinant nucleic acid of any one of claims 27-34, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 1.
36. The recombinant nucleic acid of any one of claims 27-35, further comprising a 3'UTR nucleic acid sequence.
37. The recombinant nucleic acid of claim 36, wherein said 3'UTR nucleic acid sequence is located at 3' of said mitochondrial targeting sequence.
38. The recombinant nucleic acid of claim 36 or 37, wherein said 3'UTR nucleic acid sequence comprises a sequence selected from the group consisting of hsACO2, hsATP5B, hsAK2, hsALDH2, hsCOX10, hsUQCRFS1, hsNDUFV1, hsNDUFV2, hsSOD2, hsCOX6c, hsIRP1, hsMRPS12, hsATP5J2, rnSOD2, and hsOXA1L.
39. The recombinant nucleic acid of any one of claims 36-38, wherein said 3'UTR nucleic acid sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 111-125.
40. The recombinant nucleic acid of any one of claims 36-39, wherein said 3'UTR nucleic acid sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 13 or SEQ ID NO: 14.
41. The recombinant nucleic acid of any one of claims 36-40, wherein said mitochondrial targeting sequence is located at 5' of said 3'UTR nucleic acid sequence.
42. The recombinant nucleic acid of any one of claims 36-41, wherein said mitochondrial targeting sequence is located at 3' of said mitochondrial targeting sequence.
43. The recombinant nucleic acid of any one of claims 36-42, wherein said recombinant nucleic acid comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 25-28, 39-42, 53-56, 67-70, and 81-84.
44. A viral vector comprising said recombinant nucleic acid of any one of claims 1-43.
45. The viral vector of claim 44, wherein said viral vector is an adeno-associated virus (AAV) vector.
46. The viral vector of claim 45, wherein said AAV vector is selected from the group consisting of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, AAV12, AAV13, AAV14, AAV15, and AAV16 vectors.
47. The viral vector of claim 45 or 46, wherein said AAV vector is a recombinant AAV (rAAV) vector.
48. The viral vector of claim 47, wherein said rAAV vector is rAAV2 vector.
49. A pharmaceutical composition, comprising an adeno-associated virus (AAV) comprising said recombinant nucleic acid of any one of claims 1-43.
50. The pharmaceutical composition of claim 49, further comprising a pharmaceutically acceptable excipient thereof.
51. A pharmaceutical composition, comprising said viral vector of any one of claims 44-48, and a pharmaceutically acceptable excipient thereof.
52. The pharmaceutical composition of claim 50 or 51, wherein said pharmaceutically acceptable excipient comprises phosphate-buffered saline (PBS), .alpha.,.alpha.-trehalose dehydrate, L-histidine monohydrochloride monohydrate, polysorbate 20, NaCl, NaH2PO4, Na2HPO4, KH2PO4, K2HPO4, poloxamer 188, or any combination thereof.
53. The pharmaceutical composition of claim 50 or 51, wherein said pharmaceutically acceptable excipient is selected from phosphate-buffered saline (PBS), .alpha.,.alpha.-trehalose dehydrate, L-histidine monohydrochloride monohydrate, polysorbate 20, NaCl, NaH2PO4, Na2HPO4, KH2PO4, K2HPO4, poloxamer 188, and any combination thereof.
54. The pharmaceutical composition of claim 50 or 51, wherein said pharmaceutically acceptable excipient comprises poloxamer 188.
55. The pharmaceutical composition of claim 54, wherein said pharmaceutically acceptable excipient comprises 0.0001%-0.01% poloxamer 188.
56. The pharmaceutical composition of claim 55, wherein said pharmaceutically acceptable excipient comprises 0.001% poloxamer 188.
57. The pharmaceutical composition of any one of claims 50-56, wherein said pharmaceutically acceptable excipient further comprises one or more salts.
58. The pharmaceutical composition of claim 57, wherein said one or more salts comprises NaCl, NaH2PO4, Na2HPO4, and KH2PO4.
59. The pharmaceutical composition of claim 57, wherein said one or more salts comprises 80 mM NaCl, 5 mM NaH2PO4, 40 mM Na2HPO4, and 5 mM KH2PO4.
60. The pharmaceutical composition of any one of claims 49-59, wherein said pharmaceutical composition has a pH of 6-8.
61. The pharmaceutical composition of claim 60, wherein said pharmaceutical composition has a pH of 7.2-7.4.
62. The pharmaceutical composition of claim 61, wherein said pharmaceutical composition has a pH of 7.3.
63. The pharmaceutical composition of any one of claims 49-62, wherein said pharmaceutical composition has a viral titer of at least 1.0.times.10.sup.10 vg/mL.
64. The pharmaceutical composition of claim 63, wherein said pharmaceutical composition has a viral titer of at least 5.0.times.10.sup.10 vg/mL.
65. The pharmaceutical composition of any one of claims 49-64, when said pharmaceutical composition is subject to five freeze/thaw cycles, said pharmaceutical composition retains at least 60%, 70%, 80%, or 90% of a viral titer as compared to the viral titer prior to the five freeze/thaw cycles.
66. The pharmaceutical composition of any one of claims 49-65, wherein said pharmaceutical composition, when administered to a patient with Leber's hereditary optic neuropathy, generates a higher average recovery of vision than a comparable pharmaceutical composition without said recombinant nucleic acid.
67. The pharmaceutical composition of any one of claims 49-66, wherein said pharmaceutical composition, when administered to a patient with Leber's hereditary optic neuropathy, generates a higher average recovery of vision than a comparable pharmaceutical composition comprising a recombinant nucleic acid as set forth in SEQ ID NO: 15.
68. A method of treating an eye disorder, comprising administering said pharmaceutical composition of any one of claims 49-67 to a patient in need thereof.
69. The method of claim 68, wherein said eye disorder is Leber's hereditary optic neuropathy (LHON).
70. The method of claim 68 or 69, comprising administering said pharmaceutical composition to one or both eyes of said patient.
71. The method of any one of claims 68-70, wherein said pharmaceutical composition is administered via intraocular or intravitreal injection.
72. The method of claim 71, wherein said pharmaceutical composition is administered via intravitreal injection.
73. The method of claim 72, wherein about 0.01-0.1 mL of said pharmaceutical composition is administered via intravitreal injection.
74. The method of claim 73, wherein about 0.05 mL of said pharmaceutical composition is administered via intravitreal injection.
75. The method of any one of claims 68-74, further comprising administering methylprednisolone to said patient.
76. The method of claim 75, wherein said methylprednisolone is administered prior to said intravitreal injection of said pharmaceutical composition.
77. The method of claim 75 or 76, wherein said methylprednisolone is administered orally.
78. The method of any one of claims 75-77, wherein said methylprednisolone is administered daily for at least 1, 2, 3, 4, 5, 6, or 7 days prior to said intravitreal injection of said pharmaceutical composition.
79. The method of any one of claims 75-78, wherein said methylprednisolone is administered daily.
80. The method of any one of claims 75-79, wherein a daily dosage of about 32 mg/60 kg methylprednisolone is administered.
81. The method of any one of claims 75-80, wherein said methylprednisolone is administered after said intravitreal injection of said pharmaceutical composition.
82. The method of any one of claims 75-81, further comprising administering creatine phosphate sodium to said patient.
83. The method of claim 82, wherein said creatine phosphate sodium is administered intravenously.
84. The method of any one of claims 75-83, wherein said methylprednisolone is administered intravenously or orally.
85. The method of any one of claims 75-84, comprising administering methylprednisolone intravenously for at least one day, which is followed by administering methylprednisolone orally for at least a week.
86. The method of claim 85, comprising administering methylprednisolone intravenously for about 3 days, which is followed by administering methylprednisolone orally for at least about 6 weeks.
87. The method of any one of claims 75-86, wherein said methylprednisolone is administered intravenously at a daily dose of about 80 mg/60 kg.
88. The method of any one of claims 75-87, wherein said administering said pharmaceutical composition generates a higher average recovery of vision than a comparable pharmaceutical composition without said recombinant nucleic acid.
89. The method of any one of claims 75-88, wherein said administering said pharmaceutical composition generates a higher average recovery of vision than a comparable pharmaceutical composition comprising a recombinant nucleic acid as set forth in SEQ ID NO: 25.
Description:
CROSS-REFERENCE
[0001] This application is a continuation of U.S. application Ser. No. 17/361,884, filed on Jun. 29, 2021, which is a continuation of PCT Application No. PCT/CN2020/134859, filed on Dec. 9, 2020, which claims the benefit of Chinese Application No. CN201911250082.4, filed on Dec. 9, 2019, the contents of all of which are incorporated herein by reference in their entireties.
REFERENCE TO A SEQUENCE LISTING
[0002] The instant application contains a Sequence Listing which has been submitted in ASCII format via EFS-Web and is hereby incorporated by reference in its entirety. Said ASCII copy, created on May 13, 2022, is named WNBT-011_02US_SeqList_ST25.txt and is about 303 kilobytes in size.
BACKGROUND
[0003] Leber's hereditary optic neuropathy (LHON) is a mitochondrially inherited (transmitted from mother to offspring) degeneration of retinal ganglion cells (RGCs) and their axons that leads to an acute or subacute loss of central vision; this affects predominantly young adult males. LHON is only transmitted through the mother, as it is primarily due to mutations in the mitochondrial (not nuclear) genome, and only the egg contributes mitochondria to the embryo. LHON is usually due to one of three pathogenic mitochondrial DNA (mtDNA) point mutations. These mutations are at nucleotide positions 11778 G to A (G11778A), 3460 G to A (G3460A) and 14484 T to C (T14484C), respectively in the NADH dehydrogenase subunit-4 protein (ND4), NADH dehydrogenase subunit-1 protein (ND1) and NADH dehydrogenase subunit-6 protein (ND6) subunit genes of complex I of the oxidative phosphorylation chain in mitochondria. Each mutation is believed to have significant risk of permanent loss of vision. It typically progresses within several weeks to several months without pain, until the binocular vision deteriorate to below 0.1, which seriously affects the quality of life of the patient. Two LHON mutants, G3460A and T14484C, results in the reduction of the patient's platelets isolated mitochondrial NADH dehydrogenase activity by 80%. Ninety percent of the Chinese LHON patients carry the G11778A mutation. The G11778A mutation changes an arginine into histidine in the ND4 protein, resulting the dysfunction and optic nerve damage in LHON patients. There is a need for developing compositions and methods for treating LHON with higher transfection efficiency and treatment efficacy.
SUMMARY
[0004] Disclosed here recombinant nucleic acids, pharmaceutical compositions, and methods for treating LHON. In some embodiments, disclosed herein is a recombinant nucleic acid, comprising: a mitochondrial targeting sequence; a mitochondrial protein coding sequence comprising a sequence that is at least 99% identical to SEQ ID NO: 11 or 12; and a 3'UTR nucleic acid sequence.
[0005] In some embodiments, the mitochondrial targeting sequence encodes a polypeptide comprising a peptide sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 129-159. In some embodiments, the mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 2. In some embodiments, the mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 3. In some embodiments, the mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 4. In some embodiments, the mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 5. In some embodiments, the mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 1. In some embodiments, the mitochondrial protein coding sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 12. In some embodiments, the mitochondrial protein coding sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 11. In some embodiments, the 3'UTR nucleic acid sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 111-125. In some embodiments, the 3'UTR nucleic acid sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 13 or SEQ ID NO: 14. In some embodiments, the recombinant nucleic acid comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 25-28, 39-42, 53-56, 67-70, and 81-84.
[0006] In some embodiments, the disclosure provides recombinant nucleic acids comprising a mitochondrial targeting sequence; a mitochondrial protein coding sequence comprising a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to SEQ ID NO: 11 or 12; and a 3'UTR nucleic acid sequence. In some embodiments, the mitochondrial targeting sequence comprises a sequence encodes a polypeptide selected from the group consisting of hsCOX10, hsCOX8, scRPM2, IcSirt5, tbNDUS7, ncQCR2, hsATP5G2, hsLACTB, spilv1, gmCOX2, crATP6, hsOPA1, hsSDHD, hsADCK3, osP0644B06.24-2, Neurospora crassa ATP9 (ncATP9), hsGHITM, hsNDUFAB1, hsATP5G3, crATP6_hsADCK3, ncATP9_ncATP9, zmLOC100282174, ncATP9_zmLOC100282174_spilv1_ncATP9, zmLOC100282174_hsADCK3_crATP6_hsATP5G3, zmLOC100282174_hsADCK3_hsATP5G3, ncATP9_zmLOC100282174, hsADCK3_zmLOC100282174_crATP6_hsATP5G3, crATP6_hsADCK3_zmLOC100282174_hsATP5G3, hsADCK3_zmLOC100282174, hsADCK3_zmLOC100282174_crATP6, ncATP9_zmLOC100282174_spilv1_GNFP_ncATP9, and ncATP9_zmLOC100282174_spilv1_IcSirt5_osP0644B06.24-2_hsATP5G2_ncATP9. In some embodiments, the mitochondrial targeting sequence encodes a polypeptide comprising a peptide sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 129-159. In some embodiments, the mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 2 or 3. In some embodiments, the mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 4. In some embodiments, the mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 5. In some embodiments, the mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 1. In some embodiments, the 3'UTR nucleic acid sequence is located at 3' of said mitochondrial targeting sequence. In some embodiments, the 3'UTR nucleic acid sequence comprises a sequence selected from the group consisting of hsACO2, hsATP5B, hsAK2, hsALDH2, hsCOX10, hsUQCRFS1, hsNDUFV1, hsNDUFV2, hsSOD2, hsCOX6c, hsIRP1, hsMRPS12, hsATP5J2, rnSOD2, and hsOXA1L. In some embodiments, the 3'UTR nucleic acid sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 111-125 In some embodiments, the 3'UTR nucleic acid sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 13 or SEQ ID NO: 14. In some embodiments, the mitochondrial targeting sequence is located at 5' of said 3'UTR nucleic acid sequence. In some embodiments, the mitochondrial targeting sequence is located at 3' of said mitochondrial targeting sequence. In some embodiments, the recombinant nucleic acid comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 25-28, 39-42, 53-56, 67-70, and 81-84. In some embodiments, the mitochondrial protein coding sequence encodes a mitochondrial protein comprising or consisting of a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 162.
[0007] In some embodiments, the disclosure provides recombinant nucleic acids comprising a mitochondrial protein coding sequence, wherein said mitochondrial protein coding sequence encodes a polypeptide comprising a mitochondrial protein, wherein said mitochondrial protein coding sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to SEQ ID NO: 11 or 12. In some embodiments, the recombinant nucleic acid further comprises a mitochondrial targeting sequence. In some embodiments, the mitochondrial targeting sequence comprises a sequence encodes a polypeptide selected from the group consisting of hsCOX10, hsCOX8, scRPM2, IcSirt5, tbNDUS7, ncQCR2, hsATP5G2, hsLACTB, spilv1, gmCOX2, crATP6, hsOPA1, hsSDHD, hsADCK3, osP0644B06.24-2, Neurospora crassa ATP9 (ncATP9), hsGHITM, hsNDUFAB1, hsATP5G3, crATP6_hsADCK3, ncATP9_ncATP9, zmLOC100282174, ncATP9_zmLOC100282174_spilv1_ncATP9, zmLOC100282174_hsADCK3_crATP6_hsATP5G3, zmLOC100282174_hsADCK3_hsATP5G3, ncATP9_zmLOC100282174, hsADCK3_zmLOC100282174_crATP6_hsATP5G3, crATP6_hsADCK3_zmLOC100282174_hsATP5G3, hsADCK3_zmLOC100282174, hsADCK3_zmLOC100282174_crATP6, ncATP9_zmLOC100282174_spilv1_GNFP_ncATP9, and ncATP9_zmLOC100282174_spilv1_IcSirt5_osP06441306.24-2_hsATP5G2_ncATP9- . In some embodiments, the mitochondrial targeting sequence encodes a polypeptide comprising a peptide sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 129-159. In some embodiments, the mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 2. In some embodiments, the mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 3. In some embodiments, the mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 4. In some embodiments, the mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 5. In some embodiments, the mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 1. In some embodiments, the recombinant nucleic acid further comprises a 3'UTR nucleic acid sequence. In some embodiments, the 3'UTR nucleic acid sequence is located at 3' of said mitochondrial targeting sequence. In some embodiments, the 3'UTR nucleic acid sequence comprises a sequence selected from the group consisting of hsACO2, hsATP5B, hsAK2, hsALDH2, hsCOX10, hsUQCRFS1, hsNDUFV1, hsNDUFV2, hsSOD2, hsCOX6c, hsIRP1, hsMRPS12, hsATP5J2, rnSOD2, and hsOXA1L. In some embodiments, the 3'UTR nucleic acid sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 111-125. In some embodiments, the 3'UTR nucleic acid sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 13 or SEQ ID NO: 14. In some embodiments, the mitochondrial targeting sequence is located at 5' of said 3'UTR nucleic acid sequence. In some embodiments, the mitochondrial targeting sequence is located at 3' of said mitochondrial targeting sequence. In some embodiments, the recombinant nucleic acid comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 25-28, 39-42, 53-56, 67-70, and 81-84.
[0008] In some embodiments, the disclosure provides viral vectors comprising recombinant nucleic acid of the disclosure. In some embodiments, the viral vector is an adeno-associated virus (AAV) vector. In some embodiments, the AAV vector is selected from the group consisting of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, AAV12, AAV13, AAV14, AAV15, and AAV16 vectors. In some embodiments, the AAV vector is a recombinant AAV (rAAV) vector. In some embodiments, the rAAV vector is rAAV2 vector.
[0009] In some embodiments, disclosed herein is a pharmaceutical composition, comprising an adeno-associated virus (AAV) comprising any recombinant nucleic acid disclosed herein. In some cases, the pharmaceutical composition further comprises a pharmaceutically acceptable excipient thereof. Also disclosed is a pharmaceutical composition, comprising the viral vector disclosed herein, and a pharmaceutically acceptable excipient thereof, wherein the viral vector comprises any recombinant nucleic acid disclosed herein.
[0010] In some cases, the pharmaceutically acceptable excipient comprises phosphate-buffered saline (PBS), .alpha.,.alpha.-trehalose dehydrate, L-histidine monohydrochloride monohydrate, polysorbate 20, NaCl, NaH2PO4, Na2HPO4, KH2PO4, K2HPO4, poloxamer 188, or any combination thereof. In some cases, the pharmaceutically acceptable excipient is selected from phosphate-buffered saline (PBS), .alpha.,.alpha.-trehalose dehydrate, L-histidine monohydrochloride monohydrate, polysorbate 20, NaCl, NaH2PO4, Na2HPO4, KH2PO4, K2HPO4, poloxamer 188, and any combination thereof. In some cases, the pharmaceutically acceptable excipient comprises poloxamer 188. In some cases, the pharmaceutically acceptable excipient comprises 0.0001%-0.01% poloxamer 188. In some cases, the pharmaceutically acceptable excipient comprises 0.001% poloxamer 188. In some cases, the pharmaceutically acceptable excipient further comprises one or more salts. In some cases, the one or more salts comprises NaCl, NaH2PO4, Na2HPO4, and KH2PO4. In some cases, the one or more salts comprises 80 mM NaCl, 5 mM NaH2PO4, 40 mM Na2HPO4, and 5 mM KH2PO4. In some cases, the pharmaceutical composition has a pH of 6-8. In some cases, the pharmaceutical composition has a pH of 7.2-7.4. In some cases, the pharmaceutical composition has a pH of 7.3. In some cases, the pharmaceutical composition has a viral titer of at least 1.0.times.1010 vg/mL. In some cases, the pharmaceutical composition has a viral titer of at least 5.0.times.1010 vg/mL.
[0011] In some cases, the pharmaceutical composition is subject to five freeze/thaw cycles, the pharmaceutical composition retains at least 60%, 70%, 80%, or 90% of a viral titer as compared to the viral titer prior to the five freeze/thaw cycles. In some cases, the pharmaceutical composition, when administered to a patient with Leber's hereditary optic neuropathy, generates a higher average recovery of vision than a comparable pharmaceutical composition without the recombinant nucleic acid. In some cases, the pharmaceutical composition, when administered to a patient with Leber's hereditary optic neuropathy, generates a higher average recovery of vision than a comparable pharmaceutical composition comprising a recombinant nucleic acid as set forth in SEQ ID NO: 15.
[0012] In another aspect, disclosed herein is a method of treating an eye disorder, comprising administering any pharmaceutical composition disclosed herein to a patient in need thereof. In some cases, the eye disorder is Leber's hereditary optic neuropathy (LHON). In some cases, the method comprises administering the pharmaceutical composition to one or both eyes of the patient. In some cases, the pharmaceutical composition is administered via intraocular or intravitreal injection. In some cases, the pharmaceutical composition is administered via intravitreal injection. In some cases, about 0.01-0.1 mL of the pharmaceutical composition is administered via intravitreal injection. In some cases, about 0.05 mL of the pharmaceutical composition is administered via intravitreal injection.
[0013] In some cases, the method further comprises administering methylprednisolone to the patient. In some cases, the methylprednisolone is administered prior to the intravitreal injection of the pharmaceutical composition. In some cases, the methylprednisolone is administered orally In some cases, the methylprednisolone is administered daily for at least 1, 2, 3, 4, 5, 6, or 7 days prior to the intravitreal injection of the pharmaceutical composition. In some cases, the methylprednisolone is administered daily. In some cases, the a daily dosage of about 32 mg/60 kg methylprednisolone is administered. In some cases, the methylprednisolone is administered after the intravitreal injection of the pharmaceutical composition. In some cases, the method further comprises administering creatine phosphate sodium to the patient. In some cases, the creatine phosphate sodium is administered intravenously. In some cases, the methylprednisolone is administered intravenously or orally. In some cases, the method comprises administering methylprednisolone intravenously for at least one day, which is followed by administering methylprednisolone orally for at least a week. In some cases, the method comprises administering methylprednisolone intravenously for about 3 days, which is followed by administering methylprednisolone orally for at least about 6 weeks. In some cases, the methylprednisolone is administered intravenously at a daily dose of about 80 mg/60 kg. In some cases, the administering the pharmaceutical composition generates a higher average recovery of vision than a comparable pharmaceutical composition without the recombinant nucleic acid. In some cases, the administering the pharmaceutical composition generates a higher average recovery of vision than a comparable pharmaceutical composition comprising a recombinant nucleic acid as set forth in SEQ ID NO: 25.
INCORPORATION BY REFERENCE
[0014] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:
[0016] FIG. 1 shows the codon usage frequency of non-optimized ND1 gene;
[0017] FIG. 2 shows the codon usage frequency of optimized ND1 gene;
[0018] FIG. 3 shows sequence alignment of optimized opt_ND1 gene (SEQ ID NO: 12) and ND1 gene (SEQ ID NO: 11);
[0019] FIG. 4 shows sequence alignment of COX10-opt_ND1 (SEQ ID NO: 168) and COX10-ND1 (SEQ ID NO: 169);
[0020] FIG. 5 shows the protein expression level analysis of COX10-opt_ND1 construct and COX10-ND1 construct in human HEK293 cells. Upper figure shows Western blotting result and lower figure is a bar graph showing analysis result;
[0021] FIG. 6 shows mitochondria localization assay of ND1 protein, displaying green fluorescence signal (left), MitoTracker signal (middle) and merged signals (right) showing mitochondria co-localization;
[0022] FIG. 7 shows ND1 expression dynamics in HEK293 cells transduced with rAAV2-ND1;
[0023] FIG. 8 shows change of ND1 mRNA expression level in C57BL/6J mice intravitreally injected with rAAV2-ND1;
[0024] FIG. 9 shows the ND1 protein expression level in HEK293 cells transduced with AAV2-ND1; and
[0025] FIG. 10 shows cytokine expression analysis (1-month post-injection and 2-month post-injection) of rabbit intravitreally injected with rAAV2-ND1.
DETAILED DESCRIPTION
Definitions
[0026] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of the ordinary skill in the art to which this disclosure belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the formulations or unit doses herein, some methods and materials are now described. Unless mentioned otherwise, the techniques employed or contemplated herein are standard methodologies. The materials, methods and examples are illustrative only and not limiting.
[0027] As used herein and in the appended claims, the singular forms "a," "and," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a compound" includes a plurality of such agents, and reference to "the salt" includes reference to one or more salts (or to a plurality of salts) and equivalents thereof known to those skilled in the art, and so forth.
[0028] As used herein, unless otherwise indicated, the term "or" can be conjunctive or disjunctive. As used herein, unless otherwise indicated, any embodiment can be combined with any other embodiment.
[0029] As used herein, unless otherwise indicated, some inventive embodiments herein contemplate numerical ranges. When ranges are present, the ranges include the range endpoints. Additionally, every subrange and value within the range is present as if explicitly written out.
[0030] The term "about" and its grammatical equivalents in relation to a reference numerical value and its grammatical equivalents as used herein can include a range of values plus or minus 10% from that value, such as a range of values plus or minus 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% from that value. For example, the amount "about 10" includes amounts from 9 to 11.
[0031] The term "comprising" (and related terms such as "comprise" or "comprises" or "having" or "including") is not intended to exclude that in other certain embodiments, for example, an embodiment of any composition of matter, composition, method, or process, or the like, described herein, may "consist of" or "consist essentially of" the described features.
[0032] The term "subject" refers to a mammal that has been or will be the object of treatment, observation or experiment. The term "mammal" is intended to have its standard meaning, and encompasses humans, dogs, cats, sheep, and cows, for example. The methods described herein can be useful in both human therapy and veterinary applications. In some embodiments, the subject is a human.
[0033] The term "treating" or "treatment" encompasses administration of at least one compound disclosed herein, or a pharmaceutically acceptable salt thereof, to a mammalian subject, particularly a human subject, in need of such an administration and includes (i) arresting the development of clinical symptoms of the disease, such as cancer, (ii) bringing about a regression in the clinical symptoms of the disease, such as cancer, and/or (iii) prophylactic treatment for preventing the onset of the disease, such as cancer.
[0034] The term "therapeutically effective amount" of a chemical entity described herein refers to an amount effective, when administered to a human or non-human subject, to provide a therapeutic benefit such as amelioration of symptoms, slowing of disease progression, or prevention of disease.
[0035] As used herein, unless otherwise indicated, the terms "nucleic acid" and "polynucleotide" can be used interchangeably.
Nucleic Acid and Polypeptide Sequences
[0036] Table 1 discloses all the nucleic acid and polypeptide sequences disclosed herein. The first column shows the SEQ ID NO of each sequence. The second column describes the nucleic acid or polypeptide construct. For example, the construct COX10-opt_ND1-3'UTR (SEQ ID NO: 27) is a nucleic acid combining the nucleic acid sequences of COX10 (SEQ ID NO: 1), opt_ND1 (SEQ ID NO: 12), and 3'UTR (SEQ ID NO: 13) (from 5' to 3') without linker between the nucleic acid sequences.
TABLE-US-00001 TABLE 1 nucleic acid and polypeptide sequences and SEQ ID NOs SEQ ID NO: description sequence 1 COX10 ATGGCCGCATCTCCGCACACTCTCTCCTCACGCCTCCTGACAGGTTGCGT AGGAGGCTCTGTCTGGTATCTTGAAAGAAGAACT 2 opt_COX10 ATGGCCGCCTCTCCACACACACTGAGTAGCAGACTGCTGACCGGCTGTG TTGGCGGCTCTGTGTGGTATCTGGAACGGCGGACA 3 opt_COX10* ATGGCCGCCAGCCCCCACACCCTGAGCAGCCGCCTGCTGACCGGCTGC GTGGGCGGCAGCGTGTGGTACCTGGAGCGCCGCACC 4 COX8 ATGTCCGTCCTGACGCGCCTGCTGCTGCGGGGCTTGACACGGCTCGGCT CGGCGGCTCCAGTGCGGCGCGCCAGAATCCATTCGTTG 5 OPA1 GTGCTGCCCGCCTAGAAAGGGTGAAGTGGTTGTTTCCGTGACGGACTGA GTACGGGTGCCTGTCAGGCTCTTGCGGAAGTCCATGCGCCATTGGGAGG GCCTCGGCCGCGGCTCTGTGCCCTTGCTGCTGAGGGCCACTTCCTGGGT CATTCCTGGACCGGGAGCCGGGCTGGGGCTCACACGGGGGCTCCCGCG TGGCCGTCTCGGCGCCTGCGTGACCTCCCCGCCGGCGGGATGTGGCGA CTACGTCGGGCCGCTGTGGCCTG 6 ND4 ATGCTAAAACTAATCGTCCCAACAATTATGTTACTACCACTGACATGGCTT TCCAAAAAACACATGATTTGGATCAACACAACCACCCACAGCCTAATTATT AGCATCATCCCTCTACTATTTTTTAACCAAATCAACAACAACCTATTTAGCT GTTCCCCAACCTTTTCCTCCGACCCCCTAACAACCCCCCTCCTAATGCTA ACTACCTGGCTCCTACCCCTCACAATCATGGCAAGCCAACGCCACTTATC CAGTGAACCACTATCACGAAAAAAACTCTACCTCTCTATGCTAATCTCCCT ACAAATCTCCTTAATTATGACATTCACAGCCACAGAACTAATCATGTTTTAT ATCTTCTTCGAAACCACACTTATCCCCACCTTGGCTATCATCACCCGATGG GGCAACCAGCCAGAACGCCTGAACGCAGGCACATACTTCCTATTCTACAC CCTAGTAGGCTCCCTTCCCCTACTCATCGCACTAATTTACACTCACAACAC CCTAGGCTCACTAAACATTCTACTACTCACTCTCACTGCCCAAGAACTATC AAACTCCTGGGCCAACAACTTAATGTGGCTAGCTTACACAATGGCTTTTAT GGTAAAGATGCCTCTTTACGGACTCCACTTATGGCTCCCTAAAGCCCATG TCGAAGCCCCCATCGCTGGGTCAATGGTACTTGCCGCAGTACTCTTAAAA CTAGGCGGCTATGGTATGATGCGCCTCACACTCATTCTCAACCCCCTGAC AAAACACATGGCCTACCCCTTCCTTGTACTATCCCTATGGGGCATGATTAT GACAAGCTCCATCTGCCTACGACAAACAGACCTAAAATCGCTCATTGCAT ACTCTTCAATCAGCCACATGGCCCTCGTAGTAACAGCCATTCTCATCCAA ACCCCCTGGAGCTTCACCGGCGCAGTCATTCTCATGATCGCCCACGGGC TTACATCCTCATTACTATTCTGCCTAGCAAACTCAAACTACGAACGCACTC ACAGTCGCATCATGATCCTCTCTCAAGGACTTCAAACTCTACTCCCACTAA TGGCTTTTTGGTGGCTTCTAGCAAGCCTCGCTAACCTCGCCTTACCCCCC ACTATTAACCTACTGGGAGAACTCTCTGTGCTAGTAACCACGTTCTCCTG GTCAAATATCACTCTCCTACTTACAGGACTCAACATGCTAGTCACAGCCCT ATACTCCCTCTACATGTTTACCACAACACAATGGGGCTCACTCACCCACC ACATTAACAACATGAAACCCTCATTCACACGAGAAAACACCCTCATGTTCA TGCACCTATCCCCCATTCTCCTCCTATCCCTCAACCCCGACATCATTACC GGGTTTTCCTCTTAA 7 opt_ND4 ATGCTGAAGCTGATCGTGCCCACCATCATGCTGCTGCCTCTGACCTGGCT GAGCAAGAAACACATGATCTGGATCAACACCACCACGCACAGCCTGATCA TCAGCATCATCCCTCTGCTGTTCTTCAACCAGATCAACAACAACCTGTTCA GCTGCAGCCCCACCTTCAGCAGCGACCCTCTGACAACACCTCTGCTGAT GCTGACCACCTGGCTGCTGCCCCTCACAATCATGGCCTCTCAGAGACAC CTGAGCAGCGAGCCCCTGAGCCGGAAGAAACTGTACCTGAGCATGCTGA TCTCCCTGCAGATCTCTCTGATCATGACCTTCACCGCCACCGAGCTGATC ATGTTCTACATCTTTTTCGAGACAACGCTGATCCCCACACTGGCCATCATC ACCAGATGGGGCAACCAGCCTGAGAGACTGAACGCCGGCACCTACTTTC TGTTCTACACCCTCGTGGGCAGCCTGCCACTGCTGATTGCCCTGATCTAC ACCCACAACACCCTGGGCTCCCTGAACATCCTGCTGCTGACACTGACAG CCCAAGAGCTGAGCAACAGCTGGGCCAACAATCTGATGTGGCTGGCCTA CACAATGGCCTTCATGGTCAAGATGCCCCTGTACGGCCTGCACCTGTGG CTGCCTAAAGCTCATGTGGAAGCCCCTATCGCCGGCTCTATGGTGCTGG CTGCAGTGCTGCTGAAACTCGGCGGCTACGGCATGATGCGGCTGACCCT GATTCTGAATCCCCTGACCAAGCACATGGCCTATCCATTTCTGGTGCTGA GCCTGTGGGGCATGATTATGACCAGCAGCATCTGCCTGCGGCAGACCGA TCTGAAGTCCCTGATCGCCTACAGCTCCATCAGCCACATGGCCCTGGTG GTCACCGCCATCCTGATTCAGACCCCTTGGAGCTTTACAGGCGCCGTGAT CCTGATGATTGCCCACGGCCTGACAAGCAGCCTGCTGTTTTGTCTGGCCA ACAGCAACTACGAGCGGACCCACAGCAGAATCATGATCCTGTCTCAGGG CCTGCAGACCCTCCTGCCTCTTATGGCTTTTTGGTGGCTGCTGGCCTCTC TGGCCAATCTGGCACTGCCTCCTACCATCAATCTGCTGGGCGAGCTGAG CGTGCTGGTCACCACATTCAGCTGGTCCAATATCACCCTGCTGCTCACCG GCCTGAACATGCTGGTTACAGCCCTGTACTCCCTGTACATGTTCACCACC ACACAGTGGGGAAGCCTGACACACCACATCAACAATATGAAGCCCAGCTT CACCCGCGAGAACACCCTGATGTTCATGCATCTGAGCCCCATTCTGCTGC TGTCCCTGAATCCTGATATCATCACCGGCTTCTCCAGCTGA 8 opt_ND4* ATGCTGAAGCTGATCGTGCCCACCATCATGCTGCTGCCCCTGACCTGGC TGAGCAAGAAGCACATGATCTGGATCAACACCACCACCCACAGCCTGATC ATCAGCATCATCCCCCTGCTGTTCTTCAACCAGATCAACAACAACCTGTTC AGCTGCAGCCCCACCTTCAGCAGCGACCCCCTGACCACCCCCCTGCTGA TGCTGACCACCTGGCTGCTGCCCCTGACCATCATGGCCAGCCAGCGCCA CCTGAGCAGCGAGCCCCTGAGCCGCAAGAAGCTGTACCTGAGCATGCTG ATCAGCCTGCAGATCAGCCTGATCATGACCTTCACCGCCACCGAGCTGAT CATGTTCTACATCTTCTTCGAGACCACCCTGATCCCCACCCTGGCCATCA TCACCCGCTGGGGCAACCAGCCCGAGCGCCTGAACGCCGGCACCTACTT CCTGTTCTACACCCTGGTGGGCAGCCTGCCCCTGCTGATCGCCCTGATC TACACCCACAACACCCTGGGCAGCCTGAACATCCTGCTGCTGACCCTGA CCGCCCAGGAGCTGAGCAACAGCTGGGCCAACAACCTGATGTGGCTGG CCTACACCATGGCCTTCATGGTGAAGATGCCCCTGTACGGCCTGCACCT GTGGCTGCCCAAGGCCCACGTGGAGGCCCCCATCGCCGGCAGCATGGT GCTGGCCGCCGTGCTGCTGAAGCTGGGCGGCTACGGCATGATGCGCCT GACCCTGATCCTGAACCCCCTGACCAAGCACATGGCCTACCCCTTCCTG GTGCTGAGCCTGTGGGGCATGATCATGACCAGCAGCATCTGCCTGCGCC AGACCGACCTGAAGAGCCTGATCGCCTACAGCAGCATCAGCCACATGGC CCTGGTGGTGACCGCCATCCTGATCCAGACCCCCTGGAGCTTCACCGGC GCCGTGATCCTGATGATCGCCCACGGCCTGACCAGCAGCCTGCTGTTCT GCCTGGCCAACAGCAACTACGAGCGCACCCACAGCCGCATCATGATCCT GAGCCAGGGCCTGCAGACCCTGCTGCCCCTGATGGCCTTCTGGTGGCTG CTGGCCAGCCTGGCCAACCTGGCCCTGCCCCCCACCATCAACCTGCTGG GCGAGCTGAGCGTGCTGGTGACCACCTTCAGCTGGAGCAACATCACCCT GCTGCTGACCGGCCTGAACATGCTGGTGACCGCCCTGTACAGCCTGTAC ATGTTCACCACCACCCAGTGGGGCAGCCTGACCCACCACATCAACAACAT GAAGCCCAGCTTCACCCGCGAGAACACCCTGATGTTCATGCACCTGAGC CCCATCCTGCTGCTGAGCCTGAACCCCGACATCATCACCGGCTTCAGCA GCTAA 9 ND6 ATGATGTATGCTTTGTTTCTGTTGAGTGTGGGTTTAGTAATGGGGTTTGTG GGGTTTTCTTCTAAGCCTTCTCCTATTTATGGGGGTTTAGTATTGATTGTT AGCGGTGTGGTCGGGTGTGTTATTATTCTGAATTTTGGGGGAGGTTATAT GGGTTTAATGGTTTTTTTAATTTATTTAGGGGGAATGATGGTTGTCTTTGG ATATACTACAGCGATGGCTATTGAGGAGTATCCTGAGGCATGGGGGTCA GGGGTTGAGGTCTTGGTGAGTGTTTTAGTGGGGTTAGCGATGGAGGTAG GATTGGTGCTGTGGGTGAAAGAGTATGATGGGGTGGTGGTTGTGGTAAA CTTTAATAGTGTAGGAAGCTGGATGATTTATGAAGGAGAGGGGTCAGGGT TGATTCGGGAGGATCCTATTGGTGCGGGGGCTTTGTATGATTATGGGCGT TGGTTAGTAGTAGTTACTGGTTGGACATTGTTTGTTGGTGTATATATTGTA ATTGAGATTGCTCGGGGGAATTAG 10 opt_ND6 ATGATGTACGCCCTGTTCCTGCTGAGCGTGGGCCTGGTGATGGGCTTCG TGGGCTTCAGCAGCAAGCCCAGCCCCATCTACGGCGGCCTGGTGCTGAT CGTGAGCGGCGTGGTGGGCTGCGTGATCATCCTGAACTTCGGCGGCGG CTACATGGGCCTGATGGTGTTCCTGATCTACCTGGGCGGCATGATGGTG GTGTTCGGCTACACCACCGCCATGGCCATCGAGGAGTACCCCGAGGCCT GGGGCAGCGGCGTGGAGGTGCTGGTGAGCGTGCTGGTGGGCCTGGCC ATGGAGGTGGGCCTGGTGCTGTGGGTGAAGGAGTACGACGGCGTGGTG GTGGTGGTGAACTTCAACAGCGTGGGCAGCTGGATGATCTACGAGGGCG AGGGCAGCGGCCTGATCCGCGAGGACCCCATCGGCGCCGGCGCCCTGT ACGACTACGGCCGCTGGCTGGTGGTGGTGACCGGCTGGACCCTGTTCGT GGGCGTGTACATCGTGATCGAGATCGCCCGCGGCAACTAA 11 ND1 ATGCCCATGGCCAACCTCCTACTCCTCATTGTACCCATTCTAATCGCAATG GCATTCCTAATGCTTACCGAACGAAAAATTCTAGGCTATATGCAACTACGC AAAGGCCCCAACGTTGTAGGCCCCTACGGGCTACTACAACCCTTCGCTG ACGCCATGAAACTCTTCACCAAAGAGCCCCTAAAACCCGCCACATCTACC ATCACCCTCTACATCACCGCCCCGACCTTAGCTCTCACCATCGCTCTTCT ACTATGGACCCCCCTCCCCATGCCCAACCCCCTGGTCAACCTCAACCTAG GCCTCCTATTTATTCTAGCCACCTCTAGCCTAGCCGTTTACTCAATCCTCT GGTCAGGGTGGGCATCAAACTCAAACTACGCCCTGATCGGCGCACTGCG AGCAGTAGCCCAAACAATCTCATATGAAGTCACCCTAGCCATCATTCTACT ATCAACATTACTAATGAGTGGCTCCTTTAACCTCTCCACCCTTATCACAAC ACAAGAACACCTCTGGTTACTCCTGCCATCATGGCCCTTGGCCATGATGT GGTTTATCTCCACACTAGCAGAGACCAACCGAACCCCCTTCGACCTTGCC GAAGGGGAGTCCGAACTAGTCTCAGGCTTCAACATCGAATACGCCGCAG GCCCCTTCGCCCTATTCTTCATGGCCGAATACACAAACATTATTATGATGA ACACCCTCACCACTACAATCTTCCTAGGAACAACATATGACGCACTCTCC CCTGAACTCTACACAACATATTTTGTCACCAAGACCCTACTTCTAACCTCC CTGTTCTTATGGATTCGAACAGCATACCCCCGATTCCGCTACGACCAACT CATGCACCTCCTATGGAAAAACTTCCTACCACTCACCCTAGCATTACTTAT GTGGTATGTCTCCATGCCCATTACAATCTCCAGCATTCCCCCTCAAACCTA A 12 opt_ND1 ATGCCCATGGCCAACCTGCTGCTGCTGATCGTGCCCATCCTGATCGCCAT GGCCTTCCTGATGCTGACCGAGCGCAAGATCCTGGGCTACATGCAGCTG CGCAAGGGCCCCAACGTGGTGGGCCCCTACGGCCTGCTGCAGCCCTTC GCCGACGCCATGAAGCTGTTCACCAAGGAGCCCCTGAAGCCCGCCACCA GCACCATCACCCTGTACATCACCGCCCCCACCCTGGCCCTGACCATCGC CCTGCTGCTGTGGACCCCCCTGCCCATGCCCAACCCCCTGGTGAACCTG AACCTGGGCCTGCTGTTCATCCTGGCCACCAGCAGCCTGGCCGTGTACA GCATCCTGTGGAGCGGCTGGGCCAGCAACAGCAACTACGCCCTGATCGG CGCCCTGCGCGCCGTGGCCCAGACCATCAGCTACGAGGTGACCCTGGC CATCATCCTGCTGAGCACCCTGCTGATGAGCGGCAGCTTCAACCTGAGC ACCCTGATCACCACCCAGGAGCACCTGTGGCTGCTGCTGCCCAGCTGGC CCCTGGCCATGATGTGGTTCATCAGCACCCTGGCCGAGACCAACCGCAC CCCCTTCGACCTGGCCGAGGGCGAGAGCGAGCTGGTGAGCGGCTTCAA CATCGAGTACGCCGCCGGCCCCTTCGCCCTGTTCTTCATGGCCGAGTAC ACCAACATCATCATGATGAACACCCTGACCACCACCATCTTCCTGGGCAC CACCTACGACGCCCTGAGCCCCGAGCTGTACACCACCTACTTCGTGACC AAGACCCTGCTGCTGACCAGCCTGTTCCTGTGGATCCGCACCGCCTACC CCCGCTTCCGCTACGACCAGCTGATGCACCTGCTGTGGAAGAACTTCCT GCCCCTGACCCTGGCCCTGCTGATGTGGTACGTGAGCATGCCCATCACC ATCAGCAGCATCCCCCCCCAGACCTAA 13 3'UTR GAGCACTGGGACGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGCAT GTTGTGGTAATTCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAACAA GATTATAAACGAATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTTTT TAAATATTACCCAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGTCAG TGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATCTCT CCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTACA CATACACAGCTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGCAC ACTCCACATGCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCC TCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTC GGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTC CCCACCCCACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCTAG GACCCGGCTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTTGG GAGTCTCAAGCTGGACTGCCAGCCCCTGTCCTCCCTTCACCCCCATTGC GTATGAGCATTTCAGAACTCCAAGGAGTCACAGGCATCTTTATAGTTCAC GTTAACATATAGACACTGTTGGAAGCAGTTCCTTCTAAAAGGGTAGCCCT GGACTTAATACCAGCCGGATACCTCTGGCCCCCACCCCATTACTGTACCT CTGGAGTCACTACTGTGGGTCGCCACTCCTCTGCTACACAGCACGGCTTT TTCAAGGCTGTATTGAGAAGGGAAGTTAGGAAGAAGGGTGTGCTGGGCT AACCAGCCCACAGAGCTCACATTCCTGTCCCTTGGGTGAAAAATACATGT CCATCCTGATATCTCCTGAATTCAGAAATTAGCCTCCACATGTGCAATGGC TTTAAGAGCCAGAAGCAGGGTTCTGGGAATTTTGCAAGTTACCTGTGGCC AGGTGTGGTCTCGGTTACCAAATACGGTTACCTGCAGCTTTTTAGTCCTTT GTGCTCCCACGGGTCTACAGAGTCCCATCTGCCCAAAGGTCTTGAAGCTT GACAGGATGTTTTCGATTACTCAGTCTCCCAGGGCACTACTGGTCCGTAG GATTCGATTGGTCGGGGTAGGAGAGTTAAACAACATTTAAACAGAGTTCT CTCAAAAATGTCTAAAGGGATTGTAGGTAGATAACATCCAATCACTGTTTG CACTTATCTGAAATCTTCCCTCTTGGCTGCCCCCAGGTATTTACTGTGGA GAACATTGCATAGGAATGTCTGGAAAAAGCTTCTACAACTTGTTACAGCCT TCACATTTGTAGAAGCTTT 14 3'UTR* GAGCACTGGGACGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGCAT GTTGTGGTAATTCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAACAA GATTATAAACGAATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTTTT TAAATATTACCCAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGTCAG TGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATCTCT CCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTACA CATACACAGCTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGCAC ACTCCACATGCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCC TCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTC GGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTC CCCACCCCACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCTAG GACCCGGCTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTTGG GAGTCTCAAGCTGGACTGCCA 15 COX10- ATGGCCGCATCTCCGCACACTCTCTCCTCACGCCTCCTGACAGGTTGCGT ND4- AGGAGGCTCTGTCTGGTATCTTGAAAGAAGAACTATGCTAAAACTAATCG 3'UTR TCCCAACAATTATGTTACTACCACTGACATGGCTTTCCAAAAAACACATGA TTTGGATCAACACAACCACCCACAGCCTAATTATTAGCATCATCCCTCTAC TATTTTTTAACCAAATCAACAACAACCTATTTAGCTGTTCCCCAACCTTTTC CTCCGACCCCCTAACAACCCCCCTCCTAATGCTAACTACCTGGCTCCTAC CCCTCACAATCATGGCAAGCCAACGCCACTTATCCAGTGAACCACTATCA CGAAAAAAACTCTACCTCTCTATGCTAATCTCCCTACAAATCTCCTTAATTA TGACATTCACAGCCACAGAACTAATCATGTTTTATATCTTCTTCGAAACCA CACTTATCCCCACCTTGGCTATCATCACCCGATGGGGCAACCAGCCAGAA CGCCTGAACGCAGGCACATACTTCCTATTCTACACCCTAGTAGGCTCCCT TCCCCTACTCATCGCACTAATTTACACTCACAACACCCTAGGCTCACTAAA CATTCTACTACTCACTCTCACTGCCCAAGAACTATCAAACTCCTGGGCCAA CAACTTAATGTGGCTAGCTTACACAATGGCTTTTATGGTAAAGATGCCTCT TTACGGACTCCACTTATGGCTCCCTAAAGCCCATGTCGAAGCCCCCATCG CTGGGTCAATGGTACTTGCCGCAGTACTCTTAAAACTAGGCGGCTATGGT ATGATGCGCCTCACACTCATTCTCAACCCCCTGACAAAACACATGGCCTA CCCCTTCCTTGTACTATCCCTATGGGGCATGATTATGACAAGCTCCATCT GCCTACGACAAACAGACCTAAAATCGCTCATTGCATACTCTTCAATCAGC CACATGGCCCTCGTAGTAACAGCCATTCTCATCCAAACCCCCTGGAGCTT CACCGGCGCAGTCATTCTCATGATCGCCCACGGGCTTACATCCTCATTAC TATTCTGCCTAGCAAACTCAAACTACGAACGCACTCACAGTCGCATCATG ATCCTCTCTCAAGGACTTCAAACTCTACTCCCACTAATGGCTTTTTGGTGG CTTCTAGCAAGCCTCGCTAACCTCGCCTTACCCCCCACTATTAACCTACT GGGAGAACTCTCTGTGCTAGTAACCACGTTCTCCTGGTCAAATATCACTC TCCTACTTACAGGACTCAACATGCTAGTCACAGCCCTATACTCCCTCTACA TGTTTACCACAACACAATGGGGCTCACTCACCCACCACATTAACAACATG
AAACCCTCATTCACACGAGAAAACACCCTCATGTTCATGCACCTATCCCC CATTCTCCTCCTATCCCTCAACCCCGACATCATTACCGGGTTTTCCTCTTA AGAGCACTGGGACGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGC ATGTTGTGGTAATTCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAAC AAGATTATAAACGAATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTT TTTAAATATTACCCAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGTC AGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATCT CTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTA CACATACACAGCTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGC ACACTCCACATGCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAG CCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCC TCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTT TCCCCACCCCACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCT AGGACCCGGCTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTT GGGAGTCTCAAGCTGGACTGCCAGCCCCTGTCCTCCCTTCACCCCCATT GCGTATGAGCATTTCAGAACTCCAAGGAGTCACAGGCATCTTTATAGTTC ACGTTAACATATAGACACTGTTGGAAGCAGTTCCTTCTAAAAGGGTAGCC CTGGACTTAATACCAGCCGGATACCTCTGGCCCCCACCCCATTACTGTAC CTCTGGAGTCACTACTGTGGGTCGCCACTCCTCTGCTACACAGCACGGC TTTTTCAAGGCTGTATTGAGAAGGGAAGTTAGGAAGAAGGGTGTGCTGGG CTAACCAGCCCACAGAGCTCACATTCCTGTCCCTTGGGTGAAAAATACAT GTCCATCCTGATATCTCCTGAATTCAGAAATTAGCCTCCACATGTGCAATG GCTTTAAGAGCCAGAAGCAGGGTTCTGGGAATTTTGCAAGTTACCTGTGG CCAGGTGTGGTCTCGGTTACCAAATACGGTTACCTGCAGCTTTTTAGTCC TTTGTGCTCCCACGGGTCTACAGAGTCCCATCTGCCCAAAGGTCTTGAAG CTTGACAGGATGTTTTCGATTACTCAGTCTCCCAGGGCACTACTGGTCCG TAGGATTCGATTGGTCGGGGTAGGAGAGTTAAACAACATTTAAACAGAGT TCTCTCAAAAATGTCTAAAGGGATTGTAGGTAGATAACATCCAATCACTGT TTGCACTTATCTGAAATCTTCCCTCTTGGCTGCCCCCAGGTATTTACTGTG GAGAACATTGCATAGGAATGTCTGGAAAAAGCTTCTACAACTTGTTACAG CCTTCACATTTGTAGAAGCTTT 16 COX10- ATGGCCGCATCTCCGCACACTCTCTCCTCACGCCTCCTGACAGGTTGCGT ND4- AGGAGGCTCTGTCTGGTATCTTGAAAGAAGAACTATGCTAAAACTAATCG 3'UTR* TCCCAACAATTATGTTACTACCACTGACATGGCTTTCCAAAAAACACATGA TTTGGATCAACACAACCACCCACAGCCTAATTATTAGCATCATCCCTCTAC TATTTTTTAACCAAATCAACAACAACCTATTTAGCTGTTCCCCAACCTTTTC CTCCGACCCCCTAACAACCCCCCTCCTAATGCTAACTACCTGGCTCCTAC CCCTCACAATCATGGCAAGCCAACGCCACTTATCCAGTGAACCACTATCA CGAAAAAAACTCTACCTCTCTATGCTAATCTCCCTACAAATCTCCTTAATTA TGACATTCACAGCCACAGAACTAATCATGTTTTATATCTTCTTCGAAACCA CACTTATCCCCACCTTGGCTATCATCACCCGATGGGGCAACCAGCCAGAA CGCCTGAACGCAGGCACATACTTCCTATTCTACACCCTAGTAGGCTCCCT TCCCCTACTCATCGCACTAATTTACACTCACAACACCCTAGGCTCACTAAA CATTCTACTACTCACTCTCACTGCCCAAGAACTATCAAACTCCTGGGCCAA CAACTTAATGTGGCTAGCTTACACAATGGCTTTTATGGTAAAGATGCCTCT TTACGGACTCCACTTATGGCTCCCTAAAGCCCATGTCGAAGCCCCCATCG CTGGGTCAATGGTACTTGCCGCAGTACTCTTAAAACTAGGCGGCTATGGT ATGATGCGCCTCACACTCATTCTCAACCCCCTGACAAAACACATGGCCTA CCCCTTCCTTGTACTATCCCTATGGGGCATGATTATGACAAGCTCCATCT GCCTACGACAAACAGACCTAAAATCGCTCATTGCATACTCTTCAATCAGC CACATGGCCCTCGTAGTAACAGCCATTCTCATCCAAACCCCCTGGAGCTT CACCGGCGCAGTCATTCTCATGATCGCCCACGGGCTTACATCCTCATTAC TATTCTGCCTAGCAAACTCAAACTACGAACGCACTCACAGTCGCATCATG ATCCTCTCTCAAGGACTTCAAACTCTACTCCCACTAATGGCTTTTTGGTGG CTTCTAGCAAGCCTCGCTAACCTCGCCTTACCCCCCACTATTAACCTACT GGGAGAACTCTCTGTGCTAGTAACCACGTTCTCCTGGTCAAATATCACTC TCCTACTTACAGGACTCAACATGCTAGTCACAGCCCTATACTCCCTCTACA TGTTTACCACAACACAATGGGGCTCACTCACCCACCACATTAACAACATG AAACCCTCATTCACACGAGAAAACACCCTCATGTTCATGCACCTATCCCC CATTCTCCTCCTATCCCTCAACCCCGACATCATTACCGGGTTTTCCTCTTA AGAGCACTGGGACGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGC ATGTTGTGGTAATTCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAAC AAGATTATAAACGAATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTT TTTAAATATTACCCAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGTC AGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATCT CTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTA CACATACACAGCTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGC ACACTCCACATGCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAG CCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCC TCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTT TCCCCACCCCACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCT AGGACCCGGCTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTT GGGAGTCTCAAGCTGGACTGCCA 17 COX10- ATGGCCGCATCTCCGCACACTCTCTCCTCACGCCTCCTGACAGGTTGCGT opt_ND4- AGGAGGCTCTGTCTGGTATCTTGAAAGAAGAACTATGCTGAAGCTGATCG 3'UTR TGCCCACCATCATGCTGCTGCCTCTGACCTGGCTGAGCAAGAAACACATG ATCTGGATCAACACCACCACGCACAGCCTGATCATCAGCATCATCCCTCT GCTGTTCTTCAACCAGATCAACAACAACCTGTTCAGCTGCAGCCCCACCT TCAGCAGCGACCCTCTGACAACACCTCTGCTGATGCTGACCACCTGGCT GCTGCCCCTCACAATCATGGCCTCTCAGAGACACCTGAGCAGCGAGCCC CTGAGCCGGAAGAAACTGTACCTGAGCATGCTGATCTCCCTGCAGATCTC TCTGATCATGACCTTCACCGCCACCGAGCTGATCATGTTCTACATCTTTTT CGAGACAACGCTGATCCCCACACTGGCCATCATCACCAGATGGGGCAAC CAGCCTGAGAGACTGAACGCCGGCACCTACTTTCTGTTCTACACCCTCGT GGGCAGCCTGCCACTGCTGATTGCCCTGATCTACACCCACAACACCCTG GGCTCCCTGAACATCCTGCTGCTGACACTGACAGCCCAAGAGCTGAGCA ACAGCTGGGCCAACAATCTGATGTGGCTGGCCTACACAATGGCCTTCATG GTCAAGATGCCCCTGTACGGCCTGCACCTGTGGCTGCCTAAAGCTCATG TGGAAGCCCCTATCGCCGGCTCTATGGTGCTGGCTGCAGTGCTGCTGAA ACTCGGCGGCTACGGCATGATGCGGCTGACCCTGATTCTGAATCCCCTG ACCAAGCACATGGCCTATCCATTTCTGGTGCTGAGCCTGTGGGGCATGAT TATGACCAGCAGCATCTGCCTGCGGCAGACCGATCTGAAGTCCCTGATC GCCTACAGCTCCATCAGCCACATGGCCCTGGTGGTCACCGCCATCCTGA TTCAGACCCCTTGGAGCTTTACAGGCGCCGTGATCCTGATGATTGCCCAC GGCCTGACAAGCAGCCTGCTGTTTTGTCTGGCCAACAGCAACTACGAGC GGACCCACAGCAGAATCATGATCCTGTCTCAGGGCCTGCAGACCCTCCT GCCTCTTATGGCTTTTTGGTGGCTGCTGGCCTCTCTGGCCAATCTGGCAC TGCCTCCTACCATCAATCTGCTGGGCGAGCTGAGCGTGCTGGTCACCAC ATTCAGCTGGTCCAATATCACCCTGCTGCTCACCGGCCTGAACATGCTGG TTACAGCCCTGTACTCCCTGTACATGTTCACCACCACACAGTGGGGAAGC CTGACACACCACATCAACAATATGAAGCCCAGCTTCACCCGCGAGAACAC CCTGATGTTCATGCATCTGAGCCCCATTCTGCTGCTGTCCCTGAATCCTG ATATCATCACCGGCTTCTCCAGCTGAGAGCACTGGGACGCCCACCGCCC CTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAATTCTGGAACACAAG AAGAGAAATTGCTGGGTTTAGAACAAGATTATAAACGAATTCGGTGCTCA GTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTACCCAAAATGCTCCCC AAATAAGAAATGCATCAGCTCAGTCAGTGAATACAAAAAAGGAATTATTTT TCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACCCCACCCTCTATTCT GTTTCTTCCTCCTCACATGGGGGTACACATACACAGCTTCCTCTTTTGGTT CCATCCTTACCACCACACCACACGCACACTCCACATGCCCAGCAGAGTG GCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCTGCTGTCTGTAGTTC TGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACCCCCTTCCTTGTGAC TGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCCACACATTCTCAACC ATAGTCCTTCTAACAATACCAATAGCTAGGACCCGGCTGCTGTGCACTGG GACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCAAGCTGGACTGCCA GCCCCTGTCCTCCCTTCACCCCCATTGCGTATGAGCATTTCAGAACTCCA AGGAGTCACAGGCATCTTTATAGTTCACGTTAACATATAGACACTGTTGGA AGCAGTTCCTTCTAAAAGGGTAGCCCTGGACTTAATACCAGCCGGATACC TCTGGCCCCCACCCCATTACTGTACCTCTGGAGTCACTACTGTGGGTCGC CACTCCTCTGCTACACAGCACGGCTTTTTCAAGGCTGTATTGAGAAGGGA AGTTAGGAAGAAGGGTGTGCTGGGCTAACCAGCCCACAGAGCTCACATT CCTGTCCCTTGGGTGAAAAATACATGTCCATCCTGATATCTCCTGAATTCA GAAATTAGCCTCCACATGTGCAATGGCTTTAAGAGCCAGAAGCAGGGTTC TGGGAATTTTGCAAGTTACCTGTGGCCAGGTGTGGTCTCGGTTACCAAAT ACGGTTACCTGCAGCTTTTTAGTCCTTTGTGCTCCCACGGGTCTACAGAG TCCCATCTGCCCAAAGGTCTTGAAGCTTGACAGGATGTTTTCGATTACTCA GTCTCCCAGGGCACTACTGGTCCGTAGGATTCGATTGGTCGGGGTAGGA GAGTTAAACAACATTTAAACAGAGTTCTCTCAAAAATGTCTAAAGGGATTG TAGGTAGATAACATCCAATCACTGTTTGCACTTATCTGAAATCTTCCCTCT TGGCTGCCCCCAGGTATTTACTGTGGAGAACATTGCATAGGAATGTCTGG AAAAAGCTTCTACAACTTGTTACAGCCTTCACATTTGTAGAAGCTTT 18 COX10- ATGGCCGCATCTCCGCACACTCTCTCCTCACGCCTCCTGACAGGTTGCGT opt_ND4- AGGAGGCTCTGTCTGGTATCTTGAAAGAAGAACTATGCTGAAGCTGATCG 3'UTR* TGCCCACCATCATGCTGCTGCCTCTGACCTGGCTGAGCAAGAAACACATG ATCTGGATCAACACCACCACGCACAGCCTGATCATCAGCATCATCCCTCT GCTGTTCTTCAACCAGATCAACAACAACCTGTTCAGCTGCAGCCCCACCT TCAGCAGCGACCCTCTGACAACACCTCTGCTGATGCTGACCACCTGGCT GCTGCCCCTCACAATCATGGCCTCTCAGAGACACCTGAGCAGCGAGCCC CTGAGCCGGAAGAAACTGTACCTGAGCATGCTGATCTCCCTGCAGATCTC TCTGATCATGACCTTCACCGCCACCGAGCTGATCATGTTCTACATCTTTTT CGAGACAACGCTGATCCCCACACTGGCCATCATCACCAGATGGGGCAAC CAGCCTGAGAGACTGAACGCCGGCACCTACTTTCTGTTCTACACCCTCGT GGGCAGCCTGCCACTGCTGATTGCCCTGATCTACACCCACAACACCCTG GGCTCCCTGAACATCCTGCTGCTGACACTGACAGCCCAAGAGCTGAGCA ACAGCTGGGCCAACAATCTGATGTGGCTGGCCTACACAATGGCCTTCATG GTCAAGATGCCCCTGTACGGCCTGCACCTGTGGCTGCCTAAAGCTCATG TGGAAGCCCCTATCGCCGGCTCTATGGTGCTGGCTGCAGTGCTGCTGAA ACTCGGCGGCTACGGCATGATGCGGCTGACCCTGATTCTGAATCCCCTG ACCAAGCACATGGCCTATCCATTTCTGGTGCTGAGCCTGTGGGGCATGAT TATGACCAGCAGCATCTGCCTGCGGCAGACCGATCTGAAGTCCCTGATC GCCTACAGCTCCATCAGCCACATGGCCCTGGTGGTCACCGCCATCCTGA TTCAGACCCCTTGGAGCTTTACAGGCGCCGTGATCCTGATGATTGCCCAC GGCCTGACAAGCAGCCTGCTGTTTTGTCTGGCCAACAGCAACTACGAGC GGACCCACAGCAGAATCATGATCCTGTCTCAGGGCCTGCAGACCCTCCT GCCTCTTATGGCTTTTTGGTGGCTGCTGGCCTCTCTGGCCAATCTGGCAC TGCCTCCTACCATCAATCTGCTGGGCGAGCTGAGCGTGCTGGTCACCAC ATTCAGCTGGTCCAATATCACCCTGCTGCTCACCGGCCTGAACATGCTGG TTACAGCCCTGTACTCCCTGTACATGTTCACCACCACACAGTGGGGAAGC CTGACACACCACATCAACAATATGAAGCCCAGCTTCACCCGCGAGAACAC CCTGATGTTCATGCATCTGAGCCCCATTCTGCTGCTGTCCCTGAATCCTG ATATCATCACCGGCTTCTCCAGCTGAGAGCACTGGGACGCCCACCGCCC CTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAATTCTGGAACACAAG AAGAGAAATTGCTGGGTTTAGAACAAGATTATAAACGAATTCGGTGCTCA GTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTACCCAAAATGCTCCCC AAATAAGAAATGCATCAGCTCAGTCAGTGAATACAAAAAAGGAATTATTTT TCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACCCCACCCTCTATTCT GTTTCTTCCTCCTCACATGGGGGTACACATACACAGCTTCCTCTTTTGGTT CCATCCTTACCACCACACCACACGCACACTCCACATGCCCAGCAGAGTG GCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCTGCTGTCTGTAGTTC TGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACCCCCTTCCTTGTGAC TGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCCACACATTCTCAACC ATAGTCCTTCTAACAATACCAATAGCTAGGACCCGGCTGCTGTGCACTGG GACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCAAGCTGGACTGCCA 19 COX10- ATGGCCGCATCTCCGCACACTCTCTCCTCACGCCTCCTGACAGGTTGCGT opt_ND4*- AGGAGGCTCTGTCTGGTATCTTGAAAGAAGAACTATGCTGAAGCTGATCG 3'UTR TGCCCACCATCATGCTGCTGCCCCTGACCTGGCTGAGCAAGAAGCACAT GATCTGGATCAACACCACCACCCACAGCCTGATCATCAGCATCATCCCCC TGCTGTTCTTCAACCAGATCAACAACAACCTGTTCAGCTGCAGCCCCACC TTCAGCAGCGACCCCCTGACCACCCCCCTGCTGATGCTGACCACCTGGC TGCTGCCCCTGACCATCATGGCCAGCCAGCGCCACCTGAGCAGCGAGCC CCTGAGCCGCAAGAAGCTGTACCTGAGCATGCTGATCAGCCTGCAGATC AGCCTGATCATGACCTTCACCGCCACCGAGCTGATCATGTTCTACATCTT CTTCGAGACCACCCTGATCCCCACCCTGGCCATCATCACCCGCTGGGGC AACCAGCCCGAGCGCCTGAACGCCGGCACCTACTTCCTGTTCTACACCC TGGTGGGCAGCCTGCCCCTGCTGATCGCCCTGATCTACACCCACAACAC CCTGGGCAGCCTGAACATCCTGCTGCTGACCCTGACCGCCCAGGAGCTG AGCAACAGCTGGGCCAACAACCTGATGTGGCTGGCCTACACCATGGCCT TCATGGTGAAGATGCCCCTGTACGGCCTGCACCTGTGGCTGCCCAAGGC CCACGTGGAGGCCCCCATCGCCGGCAGCATGGTGCTGGCCGCCGTGCT GCTGAAGCTGGGCGGCTACGGCATGATGCGCCTGACCCTGATCCTGAAC CCCCTGACCAAGCACATGGCCTACCCCTTCCTGGTGCTGAGCCTGTGGG GCATGATCATGACCAGCAGCATCTGCCTGCGCCAGACCGACCTGAAGAG CCTGATCGCCTACAGCAGCATCAGCCACATGGCCCTGGTGGTGACCGCC ATCCTGATCCAGACCCCCTGGAGCTTCACCGGCGCCGTGATCCTGATGA TCGCCCACGGCCTGACCAGCAGCCTGCTGTTCTGCCTGGCCAACAGCAA CTACGAGCGCACCCACAGCCGCATCATGATCCTGAGCCAGGGCCTGCAG ACCCTGCTGCCCCTGATGGCCTTCTGGTGGCTGCTGGCCAGCCTGGCCA ACCTGGCCCTGCCCCCCACCATCAACCTGCTGGGCGAGCTGAGCGTGCT GGTGACCACCTTCAGCTGGAGCAACATCACCCTGCTGCTGACCGGCCTG AACATGCTGGTGACCGCCCTGTACAGCCTGTACATGTTCACCACCACCCA GTGGGGCAGCCTGACCCACCACATCAACAACATGAAGCCCAGCTTCACC CGCGAGAACACCCTGATGTTCATGCACCTGAGCCCCATCCTGCTGCTGA GCCTGAACCCCGACATCATCACCGGCTTCAGCAGCTAAGAGCACTGGGA CGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAAT TCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAACG AATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTACC CAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACAAA AAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACC CCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACACAG CTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGCACACTCCACAT GCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCT GCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACC CCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCC ACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCGG CTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCA AGCTGGACTGCCAGCCCCTGTCCTCCCTTCACCCCCATTGCGTATGAGC ATTTCAGAACTCCAAGGAGTCACAGGCATCTTTATAGTTCACGTTAACATA TAGACACTGTTGGAAGCAGTTCCTTCTAAAAGGGTAGCCCTGGACTTAAT ACCAGCCGGATACCTCTGGCCCCCACCCCATTACTGTACCTCTGGAGTCA CTACTGTGGGTCGCCACTCCTCTGCTACACAGCACGGCTTTTTCAAGGCT GTATTGAGAAGGGAAGTTAGGAAGAAGGGTGTGCTGGGCTAACCAGCCC ACAGAGCTCACATTCCTGTCCCTTGGGTGAAAAATACATGTCCATCCTGA TATCTCCTGAATTCAGAAATTAGCCTCCACATGTGCAATGGCTTTAAGAGC CAGAAGCAGGGTTCTGGGAATTTTGCAAGTTACCTGTGGCCAGGTGTGG TCTCGGTTACCAAATACGGTTACCTGCAGCTTTTTAGTCCTTTGTGCTCCC ACGGGTCTACAGAGTCCCATCTGCCCAAAGGTCTTGAAGCTTGACAGGAT GTTTTCGATTACTCAGTCTCCCAGGGCACTACTGGTCCGTAGGATTCGAT TGGTCGGGGTAGGAGAGTTAAACAACATTTAAACAGAGTTCTCTCAAAAA TGTCTAAAGGGATTGTAGGTAGATAACATCCAATCACTGTTTGCACTTATC TGAAATCTTCCCTCTTGGCTGCCCCCAGGTATTTACTGTGGAGAACATTG CATAGGAATGTCTGGAAAAAGCTTCTACAACTTGTTACAGCCTTCACATTT GTAGAAGCTTT 20 COX10- ATGGCCGCATCTCCGCACACTCTCTCCTCACGCCTCCTGACAGGTTGCGT opt_ND4*- AGGAGGCTCTGTCTGGTATCTTGAAAGAAGAACTATGCTGAAGCTGATCG 3'UTR* TGCCCACCATCATGCTGCTGCCCCTGACCTGGCTGAGCAAGAAGCACAT GATCTGGATCAACACCACCACCCACAGCCTGATCATCAGCATCATCCCCC TGCTGTTCTTCAACCAGATCAACAACAACCTGTTCAGCTGCAGCCCCACC TTCAGCAGCGACCCCCTGACCACCCCCCTGCTGATGCTGACCACCTGGC TGCTGCCCCTGACCATCATGGCCAGCCAGCGCCACCTGAGCAGCGAGCC CCTGAGCCGCAAGAAGCTGTACCTGAGCATGCTGATCAGCCTGCAGATC AGCCTGATCATGACCTTCACCGCCACCGAGCTGATCATGTTCTACATCTT CTTCGAGACCACCCTGATCCCCACCCTGGCCATCATCACCCGCTGGGGC AACCAGCCCGAGCGCCTGAACGCCGGCACCTACTTCCTGTTCTACACCC TGGTGGGCAGCCTGCCCCTGCTGATCGCCCTGATCTACACCCACAACAC CCTGGGCAGCCTGAACATCCTGCTGCTGACCCTGACCGCCCAGGAGCTG AGCAACAGCTGGGCCAACAACCTGATGTGGCTGGCCTACACCATGGCCT
TCATGGTGAAGATGCCCCTGTACGGCCTGCACCTGTGGCTGCCCAAGGC CCACGTGGAGGCCCCCATCGCCGGCAGCATGGTGCTGGCCGCCGTGCT GCTGAAGCTGGGCGGCTACGGCATGATGCGCCTGACCCTGATCCTGAAC CCCCTGACCAAGCACATGGCCTACCCCTTCCTGGTGCTGAGCCTGTGGG GCATGATCATGACCAGCAGCATCTGCCTGCGCCAGACCGACCTGAAGAG CCTGATCGCCTACAGCAGCATCAGCCACATGGCCCTGGTGGTGACCGCC ATCCTGATCCAGACCCCCTGGAGCTTCACCGGCGCCGTGATCCTGATGA TCGCCCACGGCCTGACCAGCAGCCTGCTGTTCTGCCTGGCCAACAGCAA CTACGAGCGCACCCACAGCCGCATCATGATCCTGAGCCAGGGCCTGCAG ACCCTGCTGCCCCTGATGGCCTTCTGGTGGCTGCTGGCCAGCCTGGCCA ACCTGGCCCTGCCCCCCACCATCAACCTGCTGGGCGAGCTGAGCGTGCT GGTGACCACCTTCAGCTGGAGCAACATCACCCTGCTGCTGACCGGCCTG AACATGCTGGTGACCGCCCTGTACAGCCTGTACATGTTCACCACCACCCA GTGGGGCAGCCTGACCCACCACATCAACAACATGAAGCCCAGCTTCACC CGCGAGAACACCCTGATGTTCATGCACCTGAGCCCCATCCTGCTGCTGA GCCTGAACCCCGACATCATCACCGGCTTCAGCAGCTAAGAGCACTGGGA CGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAAT TCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAACG AATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTACC CAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACAAA AAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACC CCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACACAG CTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGCACACTCCACAT GCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCT GCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACC CCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCC ACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCGG CTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCA AGCTGGACTGCCA 21 COX10- ATGGCCGCATCTCCGCACACTCTCTCCTCACGCCTCCTGACAGGTTGCGT ND6- AGGAGGCTCTGTCTGGTATCTTGAAAGAAGAACTATGATGTATGCTTTGTT 3'UTR TCTGTTGAGTGTGGGTTTAGTAATGGGGTTTGTGGGGTTTTCTTCTAAGC CTTCTCCTATTTATGGGGGTTTAGTATTGATTGTTAGCGGTGTGGTCGGG TGTGTTATTATTCTGAATTTTGGGGGAGGTTATATGGGTTTAATGGTTTTTT TAATTTATTTAGGGGGAATGATGGTTGTCTTTGGATATACTACAGCGATGG CTATTGAGGAGTATCCTGAGGCATGGGGGTCAGGGGTTGAGGTCTTGGT GAGTGTTTTAGTGGGGTTAGCGATGGAGGTAGGATTGGTGCTGTGGGTG AAAGAGTATGATGGGGTGGTGGTTGTGGTAAACTTTAATAGTGTAGGAAG CTGGATGATTTATGAAGGAGAGGGGTCAGGGTTGATTCGGGAGGATCCT ATTGGTGCGGGGGCTTTGTATGATTATGGGCGTTGGTTAGTAGTAGTTAC TGGTTGGACATTGTTTGTTGGTGTATATATTGTAATTGAGATTGCTCGGGG GAATTAGGAGCACTGGGACGCCCACCGCCCCTTTCCCTCCGCTGCCAGG CGAGCATGTTGTGGTAATTCTGGAACACAAGAAGAGAAATTGCTGGGTTT AGAACAAGATTATAAACGAATTCGGTGCTCAGTGATCACTTGACAGTTTTT TTTTTTTTTAAATATTACCCAAAATGCTCCCCAAATAAGAAATGCATCAGCT CAGTCAGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGGTCTTTTAT ACATCTCTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCTCACATGG GGGTACACATACACAGCTTCCTCTTTTGGTTCCATCCTTACCACCACACCA CACGCACACTCCACATGCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGT GTGAGCCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAA AGGCCTCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTT TGGTTTTCCCCACCCCACACATTCTCAACCATAGTCCTTCTAACAATACCA ATAGCTAGGACCCGGCTGCTGTGCACTGGGACTGGGGATTCCACATGTT TGCCTTGGGAGTCTCAAGCTGGACTGCCAGCCCCTGTCCTCCCTTCACC CCCATTGCGTATGAGCATTTCAGAACTCCAAGGAGTCACAGGCATCTTTA TAGTTCACGTTAACATATAGACACTGTTGGAAGCAGTTCCTTCTAAAAGGG TAGCCCTGGACTTAATACCAGCCGGATACCTCTGGCCCCCACCCCATTAC TGTACCTCTGGAGTCACTACTGTGGGTCGCCACTCCTCTGCTACACAGCA CGGCTTTTTCAAGGCTGTATTGAGAAGGGAAGTTAGGAAGAAGGGTGTG CTGGGCTAACCAGCCCACAGAGCTCACATTCCTGTCCCTTGGGTGAAAAA TACATGTCCATCCTGATATCTCCTGAATTCAGAAATTAGCCTCCACATGTG CAATGGCTTTAAGAGCCAGAAGCAGGGTTCTGGGAATTTTGCAAGTTACC TGTGGCCAGGTGTGGTCTCGGTTACCAAATACGGTTACCTGCAGCTTTTT AGTCCTTTGTGCTCCCACGGGTCTACAGAGTCCCATCTGCCCAAAGGTCT TGAAGCTTGACAGGATGTTTTCGATTACTCAGTCTCCCAGGGCACTACTG GTCCGTAGGATTCGATTGGTCGGGGTAGGAGAGTTAAACAACATTTAAAC AGAGTTCTCTCAAAAATGTCTAAAGGGATTGTAGGTAGATAACATCCAATC ACTGTTTGCACTTATCTGAAATCTTCCCTCTTGGCTGCCCCCAGGTATTTA CTGTGGAGAACATTGCATAGGAATGTCTGGAAAAAGCTTCTACAACTTGTT ACAGCCTTCACATTTGTAGAAGCTTT 22 COX10- ATGGCCGCATCTCCGCACACTCTCTCCTCACGCCTCCTGACAGGTTGCGT ND6- AGGAGGCTCTGTCTGGTATCTTGAAAGAAGAACTATGATGTATGCTTTGTT 3'UTR* TCTGTTGAGTGTGGGTTTAGTAATGGGGTTTGTGGGGTTTTCTTCTAAGC CTTCTCCTATTTATGGGGGTTTAGTATTGATTGTTAGCGGTGTGGTCGGG TGTGTTATTATTCTGAATTTTGGGGGAGGTTATATGGGTTTAATGGTTTTTT TAATTTATTTAGGGGGAATGATGGTTGTCTTTGGATATACTACAGCGATGG CTATTGAGGAGTATCCTGAGGCATGGGGGTCAGGGGTTGAGGTCTTGGT GAGTGTTTTAGTGGGGTTAGCGATGGAGGTAGGATTGGTGCTGTGGGTG AAAGAGTATGATGGGGTGGTGGTTGTGGTAAACTTTAATAGTGTAGGAAG CTGGATGATTTATGAAGGAGAGGGGTCAGGGTTGATTCGGGAGGATCCT ATTGGTGCGGGGGCTTTGTATGATTATGGGCGTTGGTTAGTAGTAGTTAC TGGTTGGACATTGTTTGTTGGTGTATATATTGTAATTGAGATTGCTCGGGG GAATTAGGAGCACTGGGACGCCCACCGCCCCTTTCCCTCCGCTGCCAGG CGAGCATGTTGTGGTAATTCTGGAACACAAGAAGAGAAATTGCTGGGTTT AGAACAAGATTATAAACGAATTCGGTGCTCAGTGATCACTTGACAGTTTTT TTTTTTTTTAAATATTACCCAAAATGCTCCCCAAATAAGAAATGCATCAGCT CAGTCAGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGGTCTTTTAT ACATCTCTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCTCACATGG GGGTACACATACACAGCTTCCTCTTTTGGTTCCATCCTTACCACCACACCA CACGCACACTCCACATGCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGT GTGAGCCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAA AGGCCTCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTT TGGTTTTCCCCACCCCACACATTCTCAACCATAGTCCTTCTAACAATACCA ATAGCTAGGACCCGGCTGCTGTGCACTGGGACTGGGGATTCCACATGTT TGCCTTGGGAGTCTCAAGCTGGACTGCCA 23 COX10- ATGGCCGCATCTCCGCACACTCTCTCCTCACGCCTCCTGACAGGTTGCGT opt_ND6- AGGAGGCTCTGTCTGGTATCTTGAAAGAAGAACTATGATGTACGCCCTGT 3'UTR TCCTGCTGAGCGTGGGCCTGGTGATGGGCTTCGTGGGCTTCAGCAGCAA GCCCAGCCCCATCTACGGCGGCCTGGTGCTGATCGTGAGCGGCGTGGT GGGCTGCGTGATCATCCTGAACTTCGGCGGCGGCTACATGGGCCTGATG GTGTTCCTGATCTACCTGGGCGGCATGATGGTGGTGTTCGGCTACACCA CCGCCATGGCCATCGAGGAGTACCCCGAGGCCTGGGGCAGCGGCGTGG AGGTGCTGGTGAGCGTGCTGGTGGGCCTGGCCATGGAGGTGGGCCTGG TGCTGTGGGTGAAGGAGTACGACGGCGTGGTGGTGGTGGTGAACTTCAA CAGCGTGGGCAGCTGGATGATCTACGAGGGCGAGGGCAGCGGCCTGAT CCGCGAGGACCCCATCGGCGCCGGCGCCCTGTACGACTACGGCCGCTG GCTGGTGGTGGTGACCGGCTGGACCCTGTTCGTGGGCGTGTACATCGTG ATCGAGATCGCCCGCGGCAACTAAGAGCACTGGGACGCCCACCGCCCCT TTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAATTCTGGAACACAAGAA GAGAAATTGCTGGGTTTAGAACAAGATTATAAACGAATTCGGTGCTCAGT GATCACTTGACAGTTTTTTTTTTTTTTAAATATTACCCAAAATGCTCCCCAA ATAAGAAATGCATCAGCTCAGTCAGTGAATACAAAAAAGGAATTATTTTTC CCTTTGAGGGTCTTTTATACATCTCTCCTCCAACCCCACCCTCTATTCTGT TTCTTCCTCCTCACATGGGGGTACACATACACAGCTTCCTCTTTTGGTTCC ATCCTTACCACCACACCACACGCACACTCCACATGCCCAGCAGAGTGGC ACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCTGCTGTCTGTAGTTCTG TGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACCCCCTTCCTTGTGACTG AGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCCACACATTCTCAACCAT AGTCCTTCTAACAATACCAATAGCTAGGACCCGGCTGCTGTGCACTGGGA CTGGGGATTCCACATGTTTGCCTTGGGAGTCTCAAGCTGGACTGCCAGC CCCTGTCCTCCCTTCACCCCCATTGCGTATGAGCATTTCAGAACTCCAAG GAGTCACAGGCATCTTTATAGTTCACGTTAACATATAGACACTGTTGGAAG CAGTTCCTTCTAAAAGGGTAGCCCTGGACTTAATACCAGCCGGATACCTC TGGCCCCCACCCCATTACTGTACCTCTGGAGTCACTACTGTGGGTCGCCA CTCCTCTGCTACACAGCACGGCTTTTTCAAGGCTGTATTGAGAAGGGAAG TTAGGAAGAAGGGTGTGCTGGGCTAACCAGCCCACAGAGCTCACATTCC TGTCCCTTGGGTGAAAAATACATGTCCATCCTGATATCTCCTGAATTCAGA AATTAGCCTCCACATGTGCAATGGCTTTAAGAGCCAGAAGCAGGGTTCTG GGAATTTTGCAAGTTACCTGTGGCCAGGTGTGGTCTCGGTTACCAAATAC GGTTACCTGCAGCTTTTTAGTCCTTTGTGCTCCCACGGGTCTACAGAGTC CCATCTGCCCAAAGGTCTTGAAGCTTGACAGGATGTTTTCGATTACTCAG TCTCCCAGGGCACTACTGGTCCGTAGGATTCGATTGGTCGGGGTAGGAG AGTTAAACAACATTTAAACAGAGTTCTCTCAAAAATGTCTAAAGGGATTGT AGGTAGATAACATCCAATCACTGTTTGCACTTATCTGAAATCTTCCCTCTT GGCTGCCCCCAGGTATTTACTGTGGAGAACATTGCATAGGAATGTCTGGA AAAAGCTTCTACAACTTGTTACAGCCTTCACATTTGTAGAAGCTTT 24 COX10- ATGGCCGCATCTCCGCACACTCTCTCCTCACGCCTCCTGACAGGTTGCGT opt_ND6- AGGAGGCTCTGTCTGGTATCTTGAAAGAAGAACTATGATGTACGCCCTGT 3'UTR* TCCTGCTGAGCGTGGGCCTGGTGATGGGCTTCGTGGGCTTCAGCAGCAA GCCCAGCCCCATCTACGGCGGCCTGGTGCTGATCGTGAGCGGCGTGGT GGGCTGCGTGATCATCCTGAACTTCGGCGGCGGCTACATGGGCCTGATG GTGTTCCTGATCTACCTGGGCGGCATGATGGTGGTGTTCGGCTACACCA CCGCCATGGCCATCGAGGAGTACCCCGAGGCCTGGGGCAGCGGCGTGG AGGTGCTGGTGAGCGTGCTGGTGGGCCTGGCCATGGAGGTGGGCCTGG TGCTGTGGGTGAAGGAGTACGACGGCGTGGTGGTGGTGGTGAACTTCAA CAGCGTGGGCAGCTGGATGATCTACGAGGGCGAGGGCAGCGGCCTGAT CCGCGAGGACCCCATCGGCGCCGGCGCCCTGTACGACTACGGCCGCTG GCTGGTGGTGGTGACCGGCTGGACCCTGTTCGTGGGCGTGTACATCGTG ATCGAGATCGCCCGCGGCAACTAAGAGCACTGGGACGCCCACCGCCCCT TTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAATTCTGGAACACAAGAA GAGAAATTGCTGGGTTTAGAACAAGATTATAAACGAATTCGGTGCTCAGT GATCACTTGACAGTTTTTTTTTTTTTTAAATATTACCCAAAATGCTCCCCAA ATAAGAAATGCATCAGCTCAGTCAGTGAATACAAAAAAGGAATTATTTTTC CCTTTGAGGGTCTTTTATACATCTCTCCTCCAACCCCACCCTCTATTCTGT TTCTTCCTCCTCACATGGGGGTACACATACACAGCTTCCTCTTTTGGTTCC ATCCTTACCACCACACCACACGCACACTCCACATGCCCAGCAGAGTGGC ACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCTGCTGTCTGTAGTTCTG TGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACCCCCTTCCTTGTGACTG AGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCCACACATTCTCAACCAT AGTCCTTCTAACAATACCAATAGCTAGGACCCGGCTGCTGTGCACTGGGA CTGGGGATTCCACATGTTTGCCTTGGGAGTCTCAAGCTGGACTGCCA 25 COX10- ATGGCCGCATCTCCGCACACTCTCTCCTCACGCCTCCTGACAGGTTGCGT ND1- AGGAGGCTCTGTCTGGTATCTTGAAAGAAGAACTATGCCCATGGCCAACC 3'UTR TCCTACTCCTCATTGTACCCATTCTAATCGCAATGGCATTCCTAATGCTTA CCGAACGAAAAATTCTAGGCTATATGCAACTACGCAAAGGCCCCAACGTT GTAGGCCCCTACGGGCTACTACAACCCTTCGCTGACGCCATGAAACTCTT CACCAAAGAGCCCCTAAAACCCGCCACATCTACCATCACCCTCTACATCA CCGCCCCGACCTTAGCTCTCACCATCGCTCTTCTACTATGGACCCCCCTC CCCATGCCCAACCCCCTGGTCAACCTCAACCTAGGCCTCCTATTTATTCT AGCCACCTCTAGCCTAGCCGTTTACTCAATCCTCTGGTCAGGGTGGGCAT CAAACTCAAACTACGCCCTGATCGGCGCACTGCGAGCAGTAGCCCAAAC AATCTCATATGAAGTCACCCTAGCCATCATTCTACTATCAACATTACTAAT GAGTGGCTCCTTTAACCTCTCCACCCTTATCACAACACAAGAACACCTCT GGTTACTCCTGCCATCATGGCCCTTGGCCATGATGTGGTTTATCTCCACA CTAGCAGAGACCAACCGAACCCCCTTCGACCTTGCCGAAGGGGAGTCCG AACTAGTCTCAGGCTTCAACATCGAATACGCCGCAGGCCCCTTCGCCCTA TTCTTCATGGCCGAATACACAAACATTATTATGATGAACACCCTCACCACT ACAATCTTCCTAGGAACAACATATGACGCACTCTCCCCTGAACTCTACACA ACATATTTTGTCACCAAGACCCTACTTCTAACCTCCCTGTTCTTATGGATT CGAACAGCATACCCCCGATTCCGCTACGACCAACTCATGCACCTCCTATG GAAAAACTTCCTACCACTCACCCTAGCATTACTTATGTGGTATGTCTCCAT GCCCATTACAATCTCCAGCATTCCCCCTCAAACCTAAGAGCACTGGGACG CCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAATTCT GGAACACAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAACGAAT TCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTACCCAA AATGCTCCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACAAAAAA GGAATTATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACCCCA CCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACACAGCTTC CTCTTTTGGTTCCATCCTTACCACCACACCACACGCACACTCCACATGCC CAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCTGCT GTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACCCCC TTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCCACA CATTCTCAACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCGGCTG CTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCAAG CTGGACTGCCAGCCCCTGTCCTCCCTTCACCCCCATTGCGTATGAGCATT TCAGAACTCCAAGGAGTCACAGGCATCTTTATAGTTCACGTTAACATATAG ACACTGTTGGAAGCAGTTCCTTCTAAAAGGGTAGCCCTGGACTTAATACC AGCCGGATACCTCTGGCCCCCACCCCATTACTGTACCTCTGGAGTCACTA CTGTGGGTCGCCACTCCTCTGCTACACAGCACGGCTTTTTCAAGGCTGTA TTGAGAAGGGAAGTTAGGAAGAAGGGTGTGCTGGGCTAACCAGCCCACA GAGCTCACATTCCTGTCCCTTGGGTGAAAAATACATGTCCATCCTGATATC TCCTGAATTCAGAAATTAGCCTCCACATGTGCAATGGCTTTAAGAGCCAG AAGCAGGGTTCTGGGAATTTTGCAAGTTACCTGTGGCCAGGTGTGGTCTC GGTTACCAAATACGGTTACCTGCAGCTTTTTAGTCCTTTGTGCTCCCACG GGTCTACAGAGTCCCATCTGCCCAAAGGTCTTGAAGCTTGACAGGATGTT TTCGATTACTCAGTCTCCCAGGGCACTACTGGTCCGTAGGATTCGATTGG TCGGGGTAGGAGAGTTAAACAACATTTAAACAGAGTTCTCTCAAAAATGTC TAAAGGGATTGTAGGTAGATAACATCCAATCACTGTTTGCACTTATCTGAA ATCTTCCCTCTTGGCTGCCCCCAGGTATTTACTGTGGAGAACATTGCATA GGAATGTCTGGAAAAAGCTTCTACAACTTGTTACAGCCTTCACATTTGTAG AAGCTTT 26 COX10- ATGGCCGCATCTCCGCACACTCTCTCCTCACGCCTCCTGACAGGTTGCGT ND1- AGGAGGCTCTGTCTGGTATCTTGAAAGAAGAACTATGCCCATGGCCAACC 3'UTR* TCCTACTCCTCATTGTACCCATTCTAATCGCAATGGCATTCCTAATGCTTA CCGAACGAAAAATTCTAGGCTATATGCAACTACGCAAAGGCCCCAACGTT GTAGGCCCCTACGGGCTACTACAACCCTTCGCTGACGCCATGAAACTCTT CACCAAAGAGCCCCTAAAACCCGCCACATCTACCATCACCCTCTACATCA CCGCCCCGACCTTAGCTCTCACCATCGCTCTTCTACTATGGACCCCCCTC CCCATGCCCAACCCCCTGGTCAACCTCAACCTAGGCCTCCTATTTATTCT AGCCACCTCTAGCCTAGCCGTTTACTCAATCCTCTGGTCAGGGTGGGCAT CAAACTCAAACTACGCCCTGATCGGCGCACTGCGAGCAGTAGCCCAAAC AATCTCATATGAAGTCACCCTAGCCATCATTCTACTATCAACATTACTAAT GAGTGGCTCCTTTAACCTCTCCACCCTTATCACAACACAAGAACACCTCT GGTTACTCCTGCCATCATGGCCCTTGGCCATGATGTGGTTTATCTCCACA CTAGCAGAGACCAACCGAACCCCCTTCGACCTTGCCGAAGGGGAGTCCG AACTAGTCTCAGGCTTCAACATCGAATACGCCGCAGGCCCCTTCGCCCTA TTCTTCATGGCCGAATACACAAACATTATTATGATGAACACCCTCACCACT ACAATCTTCCTAGGAACAACATATGACGCACTCTCCCCTGAACTCTACACA ACATATTTTGTCACCAAGACCCTACTTCTAACCTCCCTGTTCTTATGGATT CGAACAGCATACCCCCGATTCCGCTACGACCAACTCATGCACCTCCTATG GAAAAACTTCCTACCACTCACCCTAGCATTACTTATGTGGTATGTCTCCAT GCCCATTACAATCTCCAGCATTCCCCCTCAAACCTAAGAGCACTGGGACG CCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAATTCT GGAACACAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAACGAAT TCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTACCCAA AATGCTCCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACAAAAAA GGAATTATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACCCCA CCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACACAGCTTC CTCTTTTGGTTCCATCCTTACCACCACACCACACGCACACTCCACATGCC CAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCTGCT GTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACCCCC TTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCCACA CATTCTCAACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCGGCTG CTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCAAG CTGGACTGCCA
27 COX10- ATGGCCGCATCTCCGCACACTCTCTCCTCACGCCTCCTGACAGGTTGCGT opt_ND1- AGGAGGCTCTGTCTGGTATCTTGAAAGAAGAACTATGCCCATGGCCAACC 3'UTR TGCTGCTGCTGATCGTGCCCATCCTGATCGCCATGGCCTTCCTGATGCTG ACCGAGCGCAAGATCCTGGGCTACATGCAGCTGCGCAAGGGCCCCAAC GTGGTGGGCCCCTACGGCCTGCTGCAGCCCTTCGCCGACGCCATGAAG CTGTTCACCAAGGAGCCCCTGAAGCCCGCCACCAGCACCATCACCCTGT ACATCACCGCCCCCACCCTGGCCCTGACCATCGCCCTGCTGCTGTGGAC CCCCCTGCCCATGCCCAACCCCCTGGTGAACCTGAACCTGGGCCTGCTG TTCATCCTGGCCACCAGCAGCCTGGCCGTGTACAGCATCCTGTGGAGCG GCTGGGCCAGCAACAGCAACTACGCCCTGATCGGCGCCCTGCGCGCCG TGGCCCAGACCATCAGCTACGAGGTGACCCTGGCCATCATCCTGCTGAG CACCCTGCTGATGAGCGGCAGCTTCAACCTGAGCACCCTGATCACCACC CAGGAGCACCTGTGGCTGCTGCTGCCCAGCTGGCCCCTGGCCATGATGT GGTTCATCAGCACCCTGGCCGAGACCAACCGCACCCCCTTCGACCTGGC CGAGGGCGAGAGCGAGCTGGTGAGCGGCTTCAACATCGAGTACGCCGC CGGCCCCTTCGCCCTGTTCTTCATGGCCGAGTACACCAACATCATCATGA TGAACACCCTGACCACCACCATCTTCCTGGGCACCACCTACGACGCCCT GAGCCCCGAGCTGTACACCACCTACTTCGTGACCAAGACCCTGCTGCTG ACCAGCCTGTTCCTGTGGATCCGCACCGCCTACCCCCGCTTCCGCTACG ACCAGCTGATGCACCTGCTGTGGAAGAACTTCCTGCCCCTGACCCTGGC CCTGCTGATGTGGTACGTGAGCATGCCCATCACCATCAGCAGCATCCCC CCCCAGACCTAAGAGCACTGGGACGCCCACCGCCCCTTTCCCTCCGCTG CCAGGCGAGCATGTTGTGGTAATTCTGGAACACAAGAAGAGAAATTGCTG GGTTTAGAACAAGATTATAAACGAATTCGGTGCTCAGTGATCACTTGACA GTTTTTTTTTTTTTTAAATATTACCCAAAATGCTCCCCAAATAAGAAATGCA TCAGCTCAGTCAGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGGTC TTTTATACATCTCTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCTCA CATGGGGGTACACATACACAGCTTCCTCTTTTGGTTCCATCCTTACCACC ACACCACACGCACACTCCACATGCCCAGCAGAGTGGCACTTGGTGGCCA GAAAGTGTGAGCCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGGTC CCTCAAAGGCCTCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCCTG CATTTTTGGTTTTCCCCACCCCACACATTCTCAACCATAGTCCTTCTAACA ATACCAATAGCTAGGACCCGGCTGCTGTGCACTGGGACTGGGGATTCCA CATGTTTGCCTTGGGAGTCTCAAGCTGGACTGCCAGCCCCTGTCCTCCCT TCACCCCCATTGCGTATGAGCATTTCAGAACTCCAAGGAGTCACAGGCAT CTTTATAGTTCACGTTAACATATAGACACTGTTGGAAGCAGTTCCTTCTAA AAGGGTAGCCCTGGACTTAATACCAGCCGGATACCTCTGGCCCCCACCC CATTACTGTACCTCTGGAGTCACTACTGTGGGTCGCCACTCCTCTGCTAC ACAGCACGGCTTTTTCAAGGCTGTATTGAGAAGGGAAGTTAGGAAGAAGG GTGTGCTGGGCTAACCAGCCCACAGAGCTCACATTCCTGTCCCTTGGGT GAAAAATACATGTCCATCCTGATATCTCCTGAATTCAGAAATTAGCCTCCA CATGTGCAATGGCTTTAAGAGCCAGAAGCAGGGTTCTGGGAATTTTGCAA GTTACCTGTGGCCAGGTGTGGTCTCGGTTACCAAATACGGTTACCTGCAG CTTTTTAGTCCTTTGTGCTCCCACGGGTCTACAGAGTCCCATCTGCCCAA AGGTCTTGAAGCTTGACAGGATGTTTTCGATTACTCAGTCTCCCAGGGCA CTACTGGTCCGTAGGATTCGATTGGTCGGGGTAGGAGAGTTAAACAACAT TTAAACAGAGTTCTCTCAAAAATGTCTAAAGGGATTGTAGGTAGATAACAT CCAATCACTGTTTGCACTTATCTGAAATCTTCCCTCTTGGCTGCCCCCAG GTATTTACTGTGGAGAACATTGCATAGGAATGTCTGGAAAAAGCTTCTACA ACTTGTTACAGCCTTCACATTTGTAGAAGCTTT 28 COX10- ATGGCCGCATCTCCGCACACTCTCTCCTCACGCCTCCTGACAGGTTGCGT opt_ND1- AGGAGGCTCTGTCTGGTATCTTGAAAGAAGAACTATGCCCATGGCCAACC 3'UTR* TGCTGCTGCTGATCGTGCCCATCCTGATCGCCATGGCCTTCCTGATGCTG ACCGAGCGCAAGATCCTGGGCTACATGCAGCTGCGCAAGGGCCCCAAC GTGGTGGGCCCCTACGGCCTGCTGCAGCCCTTCGCCGACGCCATGAAG CTGTTCACCAAGGAGCCCCTGAAGCCCGCCACCAGCACCATCACCCTGT ACATCACCGCCCCCACCCTGGCCCTGACCATCGCCCTGCTGCTGTGGAC CCCCCTGCCCATGCCCAACCCCCTGGTGAACCTGAACCTGGGCCTGCTG TTCATCCTGGCCACCAGCAGCCTGGCCGTGTACAGCATCCTGTGGAGCG GCTGGGCCAGCAACAGCAACTACGCCCTGATCGGCGCCCTGCGCGCCG TGGCCCAGACCATCAGCTACGAGGTGACCCTGGCCATCATCCTGCTGAG CACCCTGCTGATGAGCGGCAGCTTCAACCTGAGCACCCTGATCACCACC CAGGAGCACCTGTGGCTGCTGCTGCCCAGCTGGCCCCTGGCCATGATGT GGTTCATCAGCACCCTGGCCGAGACCAACCGCACCCCCTTCGACCTGGC CGAGGGCGAGAGCGAGCTGGTGAGCGGCTTCAACATCGAGTACGCCGC CGGCCCCTTCGCCCTGTTCTTCATGGCCGAGTACACCAACATCATCATGA TGAACACCCTGACCACCACCATCTTCCTGGGCACCACCTACGACGCCCT GAGCCCCGAGCTGTACACCACCTACTTCGTGACCAAGACCCTGCTGCTG ACCAGCCTGTTCCTGTGGATCCGCACCGCCTACCCCCGCTTCCGCTACG ACCAGCTGATGCACCTGCTGTGGAAGAACTTCCTGCCCCTGACCCTGGC CCTGCTGATGTGGTACGTGAGCATGCCCATCACCATCAGCAGCATCCCC CCCCAGACCTAAGAGCACTGGGACGCCCACCGCCCCTTTCCCTCCGCTG CCAGGCGAGCATGTTGTGGTAATTCTGGAACACAAGAAGAGAAATTGCTG GGTTTAGAACAAGATTATAAACGAATTCGGTGCTCAGTGATCACTTGACA GTTTTTTTTTTTTTTAAATATTACCCAAAATGCTCCCCAAATAAGAAATGCA TCAGCTCAGTCAGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGGTC TTTTATACATCTCTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCTCA CATGGGGGTACACATACACAGCTTCCTCTTTTGGTTCCATCCTTACCACC ACACCACACGCACACTCCACATGCCCAGCAGAGTGGCACTTGGTGGCCA GAAAGTGTGAGCCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGGTC CCTCAAAGGCCTCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCCTG CATTTTTGGTTTTCCCCACCCCACACATTCTCAACCATAGTCCTTCTAACA ATACCAATAGCTAGGACCCGGCTGCTGTGCACTGGGACTGGGGATTCCA CATGTTTGCCTTGGGAGTCTCAAGCTGGACTGCCA 29 opt_COX10- ATGGCCGCCTCTCCACACACACTGAGTAGCAGACTGCTGACCGGCTGTG ND4- TTGGCGGCTCTGTGTGGTATCTGGAACGGCGGACAATGCTAAAACTAATC 3'UTR GTCCCAACAATTATGTTACTACCACTGACATGGCTTTCCAAAAAACACATG ATTTGGATCAACACAACCACCCACAGCCTAATTATTAGCATCATCCCTCTA CTATTTTTTAACCAAATCAACAACAACCTATTTAGCTGTTCCCCAACCTTTT CCTCCGACCCCCTAACAACCCCCCTCCTAATGCTAACTACCTGGCTCCTA CCCCTCACAATCATGGCAAGCCAACGCCACTTATCCAGTGAACCACTATC ACGAAAAAAACTCTACCTCTCTATGCTAATCTCCCTACAAATCTCCTTAATT ATGACATTCACAGCCACAGAACTAATCATGTTTTATATCTTCTTCGAAACC ACACTTATCCCCACCTTGGCTATCATCACCCGATGGGGCAACCAGCCAGA ACGCCTGAACGCAGGCACATACTTCCTATTCTACACCCTAGTAGGCTCCC TTCCCCTACTCATCGCACTAATTTACACTCACAACACCCTAGGCTCACTAA ACATTCTACTACTCACTCTCACTGCCCAAGAACTATCAAACTCCTGGGCCA ACAACTTAATGTGGCTAGCTTACACAATGGCTTTTATGGTAAAGATGCCTC TTTACGGACTCCACTTATGGCTCCCTAAAGCCCATGTCGAAGCCCCCATC GCTGGGTCAATGGTACTTGCCGCAGTACTCTTAAAACTAGGCGGCTATGG TATGATGCGCCTCACACTCATTCTCAACCCCCTGACAAAACACATGGCCT ACCCCTTCCTTGTACTATCCCTATGGGGCATGATTATGACAAGCTCCATCT GCCTACGACAAACAGACCTAAAATCGCTCATTGCATACTCTTCAATCAGC CACATGGCCCTCGTAGTAACAGCCATTCTCATCCAAACCCCCTGGAGCTT CACCGGCGCAGTCATTCTCATGATCGCCCACGGGCTTACATCCTCATTAC TATTCTGCCTAGCAAACTCAAACTACGAACGCACTCACAGTCGCATCATG ATCCTCTCTCAAGGACTTCAAACTCTACTCCCACTAATGGCTTTTTGGTGG CTTCTAGCAAGCCTCGCTAACCTCGCCTTACCCCCCACTATTAACCTACT GGGAGAACTCTCTGTGCTAGTAACCACGTTCTCCTGGTCAAATATCACTC TCCTACTTACAGGACTCAACATGCTAGTCACAGCCCTATACTCCCTCTACA TGTTTACCACAACACAATGGGGCTCACTCACCCACCACATTAACAACATG AAACCCTCATTCACACGAGAAAACACCCTCATGTTCATGCACCTATCCCC CATTCTCCTCCTATCCCTCAACCCCGACATCATTACCGGGTTTTCCTCTTA AGAGCACTGGGACGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGC ATGTTGTGGTAATTCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAAC AAGATTATAAACGAATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTT TTTAAATATTACCCAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGTC AGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATCT CTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTA CACATACACAGCTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGC ACACTCCACATGCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAG CCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCC TCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTT TCCCCACCCCACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCT AGGACCCGGCTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTT GGGAGTCTCAAGCTGGACTGCCAGCCCCTGTCCTCCCTTCACCCCCATT GCGTATGAGCATTTCAGAACTCCAAGGAGTCACAGGCATCTTTATAGTTC ACGTTAACATATAGACACTGTTGGAAGCAGTTCCTTCTAAAAGGGTAGCC CTGGACTTAATACCAGCCGGATACCTCTGGCCCCCACCCCATTACTGTAC CTCTGGAGTCACTACTGTGGGTCGCCACTCCTCTGCTACACAGCACGGC TTTTTCAAGGCTGTATTGAGAAGGGAAGTTAGGAAGAAGGGTGTGCTGGG CTAACCAGCCCACAGAGCTCACATTCCTGTCCCTTGGGTGAAAAATACAT GTCCATCCTGATATCTCCTGAATTCAGAAATTAGCCTCCACATGTGCAATG GCTTTAAGAGCCAGAAGCAGGGTTCTGGGAATTTTGCAAGTTACCTGTGG CCAGGTGTGGTCTCGGTTACCAAATACGGTTACCTGCAGCTTTTTAGTCC TTTGTGCTCCCACGGGTCTACAGAGTCCCATCTGCCCAAAGGTCTTGAAG CTTGACAGGATGTTTTCGATTACTCAGTCTCCCAGGGCACTACTGGTCCG TAGGATTCGATTGGTCGGGGTAGGAGAGTTAAACAACATTTAAACAGAGT TCTCTCAAAAATGTCTAAAGGGATTGTAGGTAGATAACATCCAATCACTGT TTGCACTTATCTGAAATCTTCCCTCTTGGCTGCCCCCAGGTATTTACTGTG GAGAACATTGCATAGGAATGTCTGGAAAAAGCTTCTACAACTTGTTACAG CCTTCACATTTGTAGAAGCTTT 30 opt_COX10- ATGGCCGCCTCTCCACACACACTGAGTAGCAGACTGCTGACCGGCTGTG ND4- TTGGCGGCTCTGTGTGGTATCTGGAACGGCGGACAATGCTAAAACTAATC 3'UTR* GTCCCAACAATTATGTTACTACCACTGACATGGCTTTCCAAAAAACACATG ATTTGGATCAACACAACCACCCACAGCCTAATTATTAGCATCATCCCTCTA CTATTTTTTAACCAAATCAACAACAACCTATTTAGCTGTTCCCCAACCTTTT CCTCCGACCCCCTAACAACCCCCCTCCTAATGCTAACTACCTGGCTCCTA CCCCTCACAATCATGGCAAGCCAACGCCACTTATCCAGTGAACCACTATC ACGAAAAAAACTCTACCTCTCTATGCTAATCTCCCTACAAATCTCCTTAATT ATGACATTCACAGCCACAGAACTAATCATGTTTTATATCTTCTTCGAAACC ACACTTATCCCCACCTTGGCTATCATCACCCGATGGGGCAACCAGCCAGA ACGCCTGAACGCAGGCACATACTTCCTATTCTACACCCTAGTAGGCTCCC TTCCCCTACTCATCGCACTAATTTACACTCACAACACCCTAGGCTCACTAA ACATTCTACTACTCACTCTCACTGCCCAAGAACTATCAAACTCCTGGGCCA ACAACTTAATGTGGCTAGCTTACACAATGGCTTTTATGGTAAAGATGCCTC TTTACGGACTCCACTTATGGCTCCCTAAAGCCCATGTCGAAGCCCCCATC GCTGGGTCAATGGTACTTGCCGCAGTACTCTTAAAACTAGGCGGCTATGG TATGATGCGCCTCACACTCATTCTCAACCCCCTGACAAAACACATGGCCT ACCCCTTCCTTGTACTATCCCTATGGGGCATGATTATGACAAGCTCCATCT GCCTACGACAAACAGACCTAAAATCGCTCATTGCATACTCTTCAATCAGC CACATGGCCCTCGTAGTAACAGCCATTCTCATCCAAACCCCCTGGAGCTT CACCGGCGCAGTCATTCTCATGATCGCCCACGGGCTTACATCCTCATTAC TATTCTGCCTAGCAAACTCAAACTACGAACGCACTCACAGTCGCATCATG ATCCTCTCTCAAGGACTTCAAACTCTACTCCCACTAATGGCTTTTTGGTGG CTTCTAGCAAGCCTCGCTAACCTCGCCTTACCCCCCACTATTAACCTACT GGGAGAACTCTCTGTGCTAGTAACCACGTTCTCCTGGTCAAATATCACTC TCCTACTTACAGGACTCAACATGCTAGTCACAGCCCTATACTCCCTCTACA TGTTTACCACAACACAATGGGGCTCACTCACCCACCACATTAACAACATG AAACCCTCATTCACACGAGAAAACACCCTCATGTTCATGCACCTATCCCC CATTCTCCTCCTATCCCTCAACCCCGACATCATTACCGGGTTTTCCTCTTA AGAGCACTGGGACGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGC ATGTTGTGGTAATTCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAAC AAGATTATAAACGAATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTT TTTAAATATTACCCAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGTC AGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATCT CTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTA CACATACACAGCTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGC ACACTCCACATGCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAG CCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCC TCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTT TCCCCACCCCACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCT AGGACCCGGCTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTT GGGAGTCTCAAGCTGGACTGCCA 31 opt_COX10- ATGGCCGCCTCTCCACACACACTGAGTAGCAGACTGCTGACCGGCTGTG opt_ND4- TTGGCGGCTCTGTGTGGTATCTGGAACGGCGGACAATGCTGAAGCTGAT 3'UTR CGTGCCCACCATCATGCTGCTGCCTCTGACCTGGCTGAGCAAGAAACAC ATGATCTGGATCAACACCACCACGCACAGCCTGATCATCAGCATCATCCC TCTGCTGTTCTTCAACCAGATCAACAACAACCTGTTCAGCTGCAGCCCCA CCTTCAGCAGCGACCCTCTGACAACACCTCTGCTGATGCTGACCACCTG GCTGCTGCCCCTCACAATCATGGCCTCTCAGAGACACCTGAGCAGCGAG CCCCTGAGCCGGAAGAAACTGTACCTGAGCATGCTGATCTCCCTGCAGA TCTCTCTGATCATGACCTTCACCGCCACCGAGCTGATCATGTTCTACATCT TTTTCGAGACAACGCTGATCCCCACACTGGCCATCATCACCAGATGGGGC AACCAGCCTGAGAGACTGAACGCCGGCACCTACTTTCTGTTCTACACCCT CGTGGGCAGCCTGCCACTGCTGATTGCCCTGATCTACACCCACAACACC CTGGGCTCCCTGAACATCCTGCTGCTGACACTGACAGCCCAAGAGCTGA GCAACAGCTGGGCCAACAATCTGATGTGGCTGGCCTACACAATGGCCTT CATGGTCAAGATGCCCCTGTACGGCCTGCACCTGTGGCTGCCTAAAGCT CATGTGGAAGCCCCTATCGCCGGCTCTATGGTGCTGGCTGCAGTGCTGC TGAAACTCGGCGGCTACGGCATGATGCGGCTGACCCTGATTCTGAATCC CCTGACCAAGCACATGGCCTATCCATTTCTGGTGCTGAGCCTGTGGGGC ATGATTATGACCAGCAGCATCTGCCTGCGGCAGACCGATCTGAAGTCCCT GATCGCCTACAGCTCCATCAGCCACATGGCCCTGGTGGTCACCGCCATC CTGATTCAGACCCCTTGGAGCTTTACAGGCGCCGTGATCCTGATGATTGC CCACGGCCTGACAAGCAGCCTGCTGTTTTGTCTGGCCAACAGCAACTAC GAGCGGACCCACAGCAGAATCATGATCCTGTCTCAGGGCCTGCAGACCC TCCTGCCTCTTATGGCTTTTTGGTGGCTGCTGGCCTCTCTGGCCAATCTG GCACTGCCTCCTACCATCAATCTGCTGGGCGAGCTGAGCGTGCTGGTCA CCACATTCAGCTGGTCCAATATCACCCTGCTGCTCACCGGCCTGAACATG CTGGTTACAGCCCTGTACTCCCTGTACATGTTCACCACCACACAGTGGGG AAGCCTGACACACCACATCAACAATATGAAGCCCAGCTTCACCCGCGAGA ACACCCTGATGTTCATGCATCTGAGCCCCATTCTGCTGCTGTCCCTGAAT CCTGATATCATCACCGGCTTCTCCAGCTGAGAGCACTGGGACGCCCACC GCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAATTCTGGAACA CAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAACGAATTCGGTG CTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTACCCAAAATGCT CCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACAAAAAAGGAATT ATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACCCCACCCTCT ATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACACAGCTTCCTCTTT TGGTTCCATCCTTACCACCACACCACACGCACACTCCACATGCCCAGCAG AGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCTGCTGTCTGTA GTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACCCCCTTCCTTGT GACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCCACACATTCTCA ACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCGGCTGCTGTGCAC TGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCAAGCTGGACTG CCAGCCCCTGTCCTCCCTTCACCCCCATTGCGTATGAGCATTTCAGAACT CCAAGGAGTCACAGGCATCTTTATAGTTCACGTTAACATATAGACACTGTT GGAAGCAGTTCCTTCTAAAAGGGTAGCCCTGGACTTAATACCAGCCGGAT ACCTCTGGCCCCCACCCCATTACTGTACCTCTGGAGTCACTACTGTGGGT CGCCACTCCTCTGCTACACAGCACGGCTTTTTCAAGGCTGTATTGAGAAG GGAAGTTAGGAAGAAGGGTGTGCTGGGCTAACCAGCCCACAGAGCTCAC ATTCCTGTCCCTTGGGTGAAAAATACATGTCCATCCTGATATCTCCTGAAT TCAGAAATTAGCCTCCACATGTGCAATGGCTTTAAGAGCCAGAAGCAGGG TTCTGGGAATTTTGCAAGTTACCTGTGGCCAGGTGTGGTCTCGGTTACCA AATACGGTTACCTGCAGCTTTTTAGTCCTTTGTGCTCCCACGGGTCTACA GAGTCCCATCTGCCCAAAGGTCTTGAAGCTTGACAGGATGTTTTCGATTA CTCAGTCTCCCAGGGCACTACTGGTCCGTAGGATTCGATTGGTCGGGGT AGGAGAGTTAAACAACATTTAAACAGAGTTCTCTCAAAAATGTCTAAAGGG ATTGTAGGTAGATAACATCCAATCACTGTTTGCACTTATCTGAAATCTTCC CTCTTGGCTGCCCCCAGGTATTTACTGTGGAGAACATTGCATAGGAATGT CTGGAAAAAGCTTCTACAACTTGTTACAGCCTTCACATTTGTAGAAGCTTT 32 opt_COX10- ATGGCCGCCTCTCCACACACACTGAGTAGCAGACTGCTGACCGGCTGTG opt_ND4- TTGGCGGCTCTGTGTGGTATCTGGAACGGCGGACAATGCTGAAGCTGAT 3'UTR* CGTGCCCACCATCATGCTGCTGCCTCTGACCTGGCTGAGCAAGAAACAC
ATGATCTGGATCAACACCACCACGCACAGCCTGATCATCAGCATCATCCC TCTGCTGTTCTTCAACCAGATCAACAACAACCTGTTCAGCTGCAGCCCCA CCTTCAGCAGCGACCCTCTGACAACACCTCTGCTGATGCTGACCACCTG GCTGCTGCCCCTCACAATCATGGCCTCTCAGAGACACCTGAGCAGCGAG CCCCTGAGCCGGAAGAAACTGTACCTGAGCATGCTGATCTCCCTGCAGA TCTCTCTGATCATGACCTTCACCGCCACCGAGCTGATCATGTTCTACATCT TTTTCGAGACAACGCTGATCCCCACACTGGCCATCATCACCAGATGGGGC AACCAGCCTGAGAGACTGAACGCCGGCACCTACTTTCTGTTCTACACCCT CGTGGGCAGCCTGCCACTGCTGATTGCCCTGATCTACACCCACAACACC CTGGGCTCCCTGAACATCCTGCTGCTGACACTGACAGCCCAAGAGCTGA GCAACAGCTGGGCCAACAATCTGATGTGGCTGGCCTACACAATGGCCTT CATGGTCAAGATGCCCCTGTACGGCCTGCACCTGTGGCTGCCTAAAGCT CATGTGGAAGCCCCTATCGCCGGCTCTATGGTGCTGGCTGCAGTGCTGC TGAAACTCGGCGGCTACGGCATGATGCGGCTGACCCTGATTCTGAATCC CCTGACCAAGCACATGGCCTATCCATTTCTGGTGCTGAGCCTGTGGGGC ATGATTATGACCAGCAGCATCTGCCTGCGGCAGACCGATCTGAAGTCCCT GATCGCCTACAGCTCCATCAGCCACATGGCCCTGGTGGTCACCGCCATC CTGATTCAGACCCCTTGGAGCTTTACAGGCGCCGTGATCCTGATGATTGC CCACGGCCTGACAAGCAGCCTGCTGTTTTGTCTGGCCAACAGCAACTAC GAGCGGACCCACAGCAGAATCATGATCCTGTCTCAGGGCCTGCAGACCC TCCTGCCTCTTATGGCTTTTTGGTGGCTGCTGGCCTCTCTGGCCAATCTG GCACTGCCTCCTACCATCAATCTGCTGGGCGAGCTGAGCGTGCTGGTCA CCACATTCAGCTGGTCCAATATCACCCTGCTGCTCACCGGCCTGAACATG CTGGTTACAGCCCTGTACTCCCTGTACATGTTCACCACCACACAGTGGGG AAGCCTGACACACCACATCAACAATATGAAGCCCAGCTTCACCCGCGAGA ACACCCTGATGTTCATGCATCTGAGCCCCATTCTGCTGCTGTCCCTGAAT CCTGATATCATCACCGGCTTCTCCAGCTGAGAGCACTGGGACGCCCACC GCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAATTCTGGAACA CAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAACGAATTCGGTG CTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTACCCAAAATGCT CCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACAAAAAAGGAATT ATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACCCCACCCTCT ATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACACAGCTTCCTCTTT TGGTTCCATCCTTACCACCACACCACACGCACACTCCACATGCCCAGCAG AGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCTGCTGTCTGTA GTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACCCCCTTCCTTGT GACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCCACACATTCTCA ACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCGGCTGCTGTGCAC TGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCAAGCTGGACTG CCA 33 opt_COX10- ATGGCCGCCTCTCCACACACACTGAGTAGCAGACTGCTGACCGGCTGTG opt_ND4*- TTGGCGGCTCTGTGTGGTATCTGGAACGGCGGACAATGCTGAAGCTGAT 3'UTR CGTGCCCACCATCATGCTGCTGCCCCTGACCTGGCTGAGCAAGAAGCAC ATGATCTGGATCAACACCACCACCCACAGCCTGATCATCAGCATCATCCC CCTGCTGTTCTTCAACCAGATCAACAACAACCTGTTCAGCTGCAGCCCCA CCTTCAGCAGCGACCCCCTGACCACCCCCCTGCTGATGCTGACCACCTG GCTGCTGCCCCTGACCATCATGGCCAGCCAGCGCCACCTGAGCAGCGA GCCCCTGAGCCGCAAGAAGCTGTACCTGAGCATGCTGATCAGCCTGCAG ATCAGCCTGATCATGACCTTCACCGCCACCGAGCTGATCATGTTCTACAT CTTCTTCGAGACCACCCTGATCCCCACCCTGGCCATCATCACCCGCTGG GGCAACCAGCCCGAGCGCCTGAACGCCGGCACCTACTTCCTGTTCTACA CCCTGGTGGGCAGCCTGCCCCTGCTGATCGCCCTGATCTACACCCACAA CACCCTGGGCAGCCTGAACATCCTGCTGCTGACCCTGACCGCCCAGGAG CTGAGCAACAGCTGGGCCAACAACCTGATGTGGCTGGCCTACACCATGG CCTTCATGGTGAAGATGCCCCTGTACGGCCTGCACCTGTGGCTGCCCAA GGCCCACGTGGAGGCCCCCATCGCCGGCAGCATGGTGCTGGCCGCCGT GCTGCTGAAGCTGGGCGGCTACGGCATGATGCGCCTGACCCTGATCCTG AACCCCCTGACCAAGCACATGGCCTACCCCTTCCTGGTGCTGAGCCTGT GGGGCATGATCATGACCAGCAGCATCTGCCTGCGCCAGACCGACCTGAA GAGCCTGATCGCCTACAGCAGCATCAGCCACATGGCCCTGGTGGTGACC GCCATCCTGATCCAGACCCCCTGGAGCTTCACCGGCGCCGTGATCCTGA TGATCGCCCACGGCCTGACCAGCAGCCTGCTGTTCTGCCTGGCCAACAG CAACTACGAGCGCACCCACAGCCGCATCATGATCCTGAGCCAGGGCCTG CAGACCCTGCTGCCCCTGATGGCCTTCTGGTGGCTGCTGGCCAGCCTGG CCAACCTGGCCCTGCCCCCCACCATCAACCTGCTGGGCGAGCTGAGCGT GCTGGTGACCACCTTCAGCTGGAGCAACATCACCCTGCTGCTGACCGGC CTGAACATGCTGGTGACCGCCCTGTACAGCCTGTACATGTTCACCACCAC CCAGTGGGGCAGCCTGACCCACCACATCAACAACATGAAGCCCAGCTTC ACCCGCGAGAACACCCTGATGTTCATGCACCTGAGCCCCATCCTGCTGC TGAGCCTGAACCCCGACATCATCACCGGCTTCAGCAGCTAAGAGCACTG GGACGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGT AATTCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAA CGAATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTA CCCAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACA AAAAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAAC CCCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACACA GCTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGCACACTCCAC ATGCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGAT CTGCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCA CCCCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACC CCACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCG GCTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCT CAAGCTGGACTGCCAGCCCCTGTCCTCCCTTCACCCCCATTGCGTATGA GCATTTCAGAACTCCAAGGAGTCACAGGCATCTTTATAGTTCACGTTAACA TATAGACACTGTTGGAAGCAGTTCCTTCTAAAAGGGTAGCCCTGGACTTA ATACCAGCCGGATACCTCTGGCCCCCACCCCATTACTGTACCTCTGGAGT CACTACTGTGGGTCGCCACTCCTCTGCTACACAGCACGGCTTTTTCAAGG CTGTATTGAGAAGGGAAGTTAGGAAGAAGGGTGTGCTGGGCTAACCAGC CCACAGAGCTCACATTCCTGTCCCTTGGGTGAAAAATACATGTCCATCCT GATATCTCCTGAATTCAGAAATTAGCCTCCACATGTGCAATGGCTTTAAGA GCCAGAAGCAGGGTTCTGGGAATTTTGCAAGTTACCTGTGGCCAGGTGT GGTCTCGGTTACCAAATACGGTTACCTGCAGCTTTTTAGTCCTTTGTGCTC CCACGGGTCTACAGAGTCCCATCTGCCCAAAGGTCTTGAAGCTTGACAG GATGTTTTCGATTACTCAGTCTCCCAGGGCACTACTGGTCCGTAGGATTC GATTGGTCGGGGTAGGAGAGTTAAACAACATTTAAACAGAGTTCTCTCAA AAATGTCTAAAGGGATTGTAGGTAGATAACATCCAATCACTGTTTGCACTT ATCTGAAATCTTCCCTCTTGGCTGCCCCCAGGTATTTACTGTGGAGAACA TTGCATAGGAATGTCTGGAAAAAGCTTCTACAACTTGTTACAGCCTTCACA TTTGTAGAAGCTTT 34 opt_COX10- ATGGCCGCCTCTCCACACACACTGAGTAGCAGACTGCTGACCGGCTGTG opt_ND4*- TTGGCGGCTCTGTGTGGTATCTGGAACGGCGGACAATGCTGAAGCTGAT 3'UTR* CGTGCCCACCATCATGCTGCTGCCCCTGACCTGGCTGAGCAAGAAGCAC ATGATCTGGATCAACACCACCACCCACAGCCTGATCATCAGCATCATCCC CCTGCTGTTCTTCAACCAGATCAACAACAACCTGTTCAGCTGCAGCCCCA CCTTCAGCAGCGACCCCCTGACCACCCCCCTGCTGATGCTGACCACCTG GCTGCTGCCCCTGACCATCATGGCCAGCCAGCGCCACCTGAGCAGCGA GCCCCTGAGCCGCAAGAAGCTGTACCTGAGCATGCTGATCAGCCTGCAG ATCAGCCTGATCATGACCTTCACCGCCACCGAGCTGATCATGTTCTACAT CTTCTTCGAGACCACCCTGATCCCCACCCTGGCCATCATCACCCGCTGG GGCAACCAGCCCGAGCGCCTGAACGCCGGCACCTACTTCCTGTTCTACA CCCTGGTGGGCAGCCTGCCCCTGCTGATCGCCCTGATCTACACCCACAA CACCCTGGGCAGCCTGAACATCCTGCTGCTGACCCTGACCGCCCAGGAG CTGAGCAACAGCTGGGCCAACAACCTGATGTGGCTGGCCTACACCATGG CCTTCATGGTGAAGATGCCCCTGTACGGCCTGCACCTGTGGCTGCCCAA GGCCCACGTGGAGGCCCCCATCGCCGGCAGCATGGTGCTGGCCGCCGT GCTGCTGAAGCTGGGCGGCTACGGCATGATGCGCCTGACCCTGATCCTG AACCCCCTGACCAAGCACATGGCCTACCCCTTCCTGGTGCTGAGCCTGT GGGGCATGATCATGACCAGCAGCATCTGCCTGCGCCAGACCGACCTGAA GAGCCTGATCGCCTACAGCAGCATCAGCCACATGGCCCTGGTGGTGACC GCCATCCTGATCCAGACCCCCTGGAGCTTCACCGGCGCCGTGATCCTGA TGATCGCCCACGGCCTGACCAGCAGCCTGCTGTTCTGCCTGGCCAACAG CAACTACGAGCGCACCCACAGCCGCATCATGATCCTGAGCCAGGGCCTG CAGACCCTGCTGCCCCTGATGGCCTTCTGGTGGCTGCTGGCCAGCCTGG CCAACCTGGCCCTGCCCCCCACCATCAACCTGCTGGGCGAGCTGAGCGT GCTGGTGACCACCTTCAGCTGGAGCAACATCACCCTGCTGCTGACCGGC CTGAACATGCTGGTGACCGCCCTGTACAGCCTGTACATGTTCACCACCAC CCAGTGGGGCAGCCTGACCCACCACATCAACAACATGAAGCCCAGCTTC ACCCGCGAGAACACCCTGATGTTCATGCACCTGAGCCCCATCCTGCTGC TGAGCCTGAACCCCGACATCATCACCGGCTTCAGCAGCTAAGAGCACTG GGACGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGT AATTCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAA CGAATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTA CCCAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACA AAAAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAAC CCCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACACA GCTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGCACACTCCAC ATGCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGAT CTGCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCA CCCCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACC CCACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCG GCTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCT CAAGCTGGACTGCCA 35 opt_COX10- ATGGCCGCCTCTCCACACACACTGAGTAGCAGACTGCTGACCGGCTGTG ND6- TTGGCGGCTCTGTGTGGTATCTGGAACGGCGGACAATGATGTATGCTTTG 3'UTR TTTCTGTTGAGTGTGGGTTTAGTAATGGGGTTTGTGGGGTTTTCTTCTAAG CCTTCTCCTATTTATGGGGGTTTAGTATTGATTGTTAGCGGTGTGGTCGG GTGTGTTATTATTCTGAATTTTGGGGGAGGTTATATGGGTTTAATGGTTTT TTTAATTTATTTAGGGGGAATGATGGTTGTCTTTGGATATACTACAGCGAT GGCTATTGAGGAGTATCCTGAGGCATGGGGGTCAGGGGTTGAGGTCTTG GTGAGTGTTTTAGTGGGGTTAGCGATGGAGGTAGGATTGGTGCTGTGGG TGAAAGAGTATGATGGGGTGGTGGTTGTGGTAAACTTTAATAGTGTAGGA AGCTGGATGATTTATGAAGGAGAGGGGTCAGGGTTGATTCGGGAGGATC CTATTGGTGCGGGGGCTTTGTATGATTATGGGCGTTGGTTAGTAGTAGTT ACTGGTTGGACATTGTTTGTTGGTGTATATATTGTAATTGAGATTGCTCGG GGGAATTAGGAGCACTGGGACGCCCACCGCCCCTTTCCCTCCGCTGCCA GGCGAGCATGTTGTGGTAATTCTGGAACACAAGAAGAGAAATTGCTGGGT TTAGAACAAGATTATAAACGAATTCGGTGCTCAGTGATCACTTGACAGTTT TTTTTTTTTTTAAATATTACCCAAAATGCTCCCCAAATAAGAAATGCATCAG CTCAGTCAGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGGTCTTTT ATACATCTCTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCTCACAT GGGGGTACACATACACAGCTTCCTCTTTTGGTTCCATCCTTACCACCACA CCACACGCACACTCCACATGCCCAGCAGAGTGGCACTTGGTGGCCAGAA AGTGTGAGCCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGGTCCCT CAAAGGCCTCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCCTGCAT TTTTGGTTTTCCCCACCCCACACATTCTCAACCATAGTCCTTCTAACAATA CCAATAGCTAGGACCCGGCTGCTGTGCACTGGGACTGGGGATTCCACAT GTTTGCCTTGGGAGTCTCAAGCTGGACTGCCAGCCCCTGTCCTCCCTTCA CCCCCATTGCGTATGAGCATTTCAGAACTCCAAGGAGTCACAGGCATCTT TATAGTTCACGTTAACATATAGACACTGTTGGAAGCAGTTCCTTCTAAAAG GGTAGCCCTGGACTTAATACCAGCCGGATACCTCTGGCCCCCACCCCAT TACTGTACCTCTGGAGTCACTACTGTGGGTCGCCACTCCTCTGCTACACA GCACGGCTTTTTCAAGGCTGTATTGAGAAGGGAAGTTAGGAAGAAGGGT GTGCTGGGCTAACCAGCCCACAGAGCTCACATTCCTGTCCCTTGGGTGA AAAATACATGTCCATCCTGATATCTCCTGAATTCAGAAATTAGCCTCCACA TGTGCAATGGCTTTAAGAGCCAGAAGCAGGGTTCTGGGAATTTTGCAAGT TACCTGTGGCCAGGTGTGGTCTCGGTTACCAAATACGGTTACCTGCAGCT TTTTAGTCCTTTGTGCTCCCACGGGTCTACAGAGTCCCATCTGCCCAAAG GTCTTGAAGCTTGACAGGATGTTTTCGATTACTCAGTCTCCCAGGGCACT ACTGGTCCGTAGGATTCGATTGGTCGGGGTAGGAGAGTTAAACAACATTT AAACAGAGTTCTCTCAAAAATGTCTAAAGGGATTGTAGGTAGATAACATCC AATCACTGTTTGCACTTATCTGAAATCTTCCCTCTTGGCTGCCCCCAGGTA TTTACTGTGGAGAACATTGCATAGGAATGTCTGGAAAAAGCTTCTACAACT TGTTACAGCCTTCACATTTGTAGAAGCTTT 36 opt_COX10- ATGGCCGCCTCTCCACACACACTGAGTAGCAGACTGCTGACCGGCTGTG ND6- TTGGCGGCTCTGTGTGGTATCTGGAACGGCGGACAATGATGTATGCTTTG 3'UTR* TTTCTGTTGAGTGTGGGTTTAGTAATGGGGTTTGTGGGGTTTTCTTCTAAG CCTTCTCCTATTTATGGGGGTTTAGTATTGATTGTTAGCGGTGTGGTCGG GTGTGTTATTATTCTGAATTTTGGGGGAGGTTATATGGGTTTAATGGTTTT TTTAATTTATTTAGGGGGAATGATGGTTGTCTTTGGATATACTACAGCGAT GGCTATTGAGGAGTATCCTGAGGCATGGGGGTCAGGGGTTGAGGTCTTG GTGAGTGTTTTAGTGGGGTTAGCGATGGAGGTAGGATTGGTGCTGTGGG TGAAAGAGTATGATGGGGTGGTGGTTGTGGTAAACTTTAATAGTGTAGGA AGCTGGATGATTTATGAAGGAGAGGGGTCAGGGTTGATTCGGGAGGATC CTATTGGTGCGGGGGCTTTGTATGATTATGGGCGTTGGTTAGTAGTAGTT ACTGGTTGGACATTGTTTGTTGGTGTATATATTGTAATTGAGATTGCTCGG GGGAATTAGGAGCACTGGGACGCCCACCGCCCCTTTCCCTCCGCTGCCA GGCGAGCATGTTGTGGTAATTCTGGAACACAAGAAGAGAAATTGCTGGGT TTAGAACAAGATTATAAACGAATTCGGTGCTCAGTGATCACTTGACAGTTT TTTTTTTTTTTAAATATTACCCAAAATGCTCCCCAAATAAGAAATGCATCAG CTCAGTCAGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGGTCTTTT ATACATCTCTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCTCACAT GGGGGTACACATACACAGCTTCCTCTTTTGGTTCCATCCTTACCACCACA CCACACGCACACTCCACATGCCCAGCAGAGTGGCACTTGGTGGCCAGAA AGTGTGAGCCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGGTCCCT CAAAGGCCTCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCCTGCAT TTTTGGTTTTCCCCACCCCACACATTCTCAACCATAGTCCTTCTAACAATA CCAATAGCTAGGACCCGGCTGCTGTGCACTGGGACTGGGGATTCCACAT GTTTGCCTTGGGAGTCTCAAGCTGGACTGCCA 37 opt_COX10- ATGGCCGCCTCTCCACACACACTGAGTAGCAGACTGCTGACCGGCTGTG opt_ND6- TTGGCGGCTCTGTGTGGTATCTGGAACGGCGGACAATGATGTACGCCCT 3'UTR GTTCCTGCTGAGCGTGGGCCTGGTGATGGGCTTCGTGGGCTTCAGCAGC AAGCCCAGCCCCATCTACGGCGGCCTGGTGCTGATCGTGAGCGGCGTG GTGGGCTGCGTGATCATCCTGAACTTCGGCGGCGGCTACATGGGCCTGA TGGTGTTCCTGATCTACCTGGGCGGCATGATGGTGGTGTTCGGCTACAC CACCGCCATGGCCATCGAGGAGTACCCCGAGGCCTGGGGCAGCGGCGT GGAGGTGCTGGTGAGCGTGCTGGTGGGCCTGGCCATGGAGGTGGGCCT GGTGCTGTGGGTGAAGGAGTACGACGGCGTGGTGGTGGTGGTGAACTT CAACAGCGTGGGCAGCTGGATGATCTACGAGGGCGAGGGCAGCGGCCT GATCCGCGAGGACCCCATCGGCGCCGGCGCCCTGTACGACTACGGCCG CTGGCTGGTGGTGGTGACCGGCTGGACCCTGTTCGTGGGCGTGTACATC GTGATCGAGATCGCCCGCGGCAACTAAGAGCACTGGGACGCCCACCGC CCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAATTCTGGAACACA AGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAACGAATTCGGTGCT CAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTACCCAAAATGCTCC CCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACAAAAAAGGAATTATT TTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACCCCACCCTCTATT CTGTTTCTTCCTCCTCACATGGGGGTACACATACACAGCTTCCTCTTTTGG TTCCATCCTTACCACCACACCACACGCACACTCCACATGCCCAGCAGAGT GGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCTGCTGTCTGTAGTT CTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACCCCCTTCCTTGTGA CTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCCACACATTCTCAAC CATAGTCCTTCTAACAATACCAATAGCTAGGACCCGGCTGCTGTGCACTG GGACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCAAGCTGGACTGCC AGCCCCTGTCCTCCCTTCACCCCCATTGCGTATGAGCATTTCAGAACTCC AAGGAGTCACAGGCATCTTTATAGTTCACGTTAACATATAGACACTGTTGG AAGCAGTTCCTTCTAAAAGGGTAGCCCTGGACTTAATACCAGCCGGATAC CTCTGGCCCCCACCCCATTACTGTACCTCTGGAGTCACTACTGTGGGTCG CCACTCCTCTGCTACACAGCACGGCTTTTTCAAGGCTGTATTGAGAAGGG AAGTTAGGAAGAAGGGTGTGCTGGGCTAACCAGCCCACAGAGCTCACAT TCCTGTCCCTTGGGTGAAAAATACATGTCCATCCTGATATCTCCTGAATTC AGAAATTAGCCTCCACATGTGCAATGGCTTTAAGAGCCAGAAGCAGGGTT CTGGGAATTTTGCAAGTTACCTGTGGCCAGGTGTGGTCTCGGTTACCAAA TACGGTTACCTGCAGCTTTTTAGTCCTTTGTGCTCCCACGGGTCTACAGA GTCCCATCTGCCCAAAGGTCTTGAAGCTTGACAGGATGTTTTCGATTACT CAGTCTCCCAGGGCACTACTGGTCCGTAGGATTCGATTGGTCGGGGTAG GAGAGTTAAACAACATTTAAACAGAGTTCTCTCAAAAATGTCTAAAGGGAT
TGTAGGTAGATAACATCCAATCACTGTTTGCACTTATCTGAAATCTTCCCT CTTGGCTGCCCCCAGGTATTTACTGTGGAGAACATTGCATAGGAATGTCT GGAAAAAGCTTCTACAACTTGTTACAGCCTTCACATTTGTAGAAGCTTT 38 opt_COX10- ATGGCCGCCTCTCCACACACACTGAGTAGCAGACTGCTGACCGGCTGTG opt_ND6- TTGGCGGCTCTGTGTGGTATCTGGAACGGCGGACAATGATGTACGCCCT 3'UTR* GTTCCTGCTGAGCGTGGGCCTGGTGATGGGCTTCGTGGGCTTCAGCAGC AAGCCCAGCCCCATCTACGGCGGCCTGGTGCTGATCGTGAGCGGCGTG GTGGGCTGCGTGATCATCCTGAACTTCGGCGGCGGCTACATGGGCCTGA TGGTGTTCCTGATCTACCTGGGCGGCATGATGGTGGTGTTCGGCTACAC CACCGCCATGGCCATCGAGGAGTACCCCGAGGCCTGGGGCAGCGGCGT GGAGGTGCTGGTGAGCGTGCTGGTGGGCCTGGCCATGGAGGTGGGCCT GGTGCTGTGGGTGAAGGAGTACGACGGCGTGGTGGTGGTGGTGAACTT CAACAGCGTGGGCAGCTGGATGATCTACGAGGGCGAGGGCAGCGGCCT GATCCGCGAGGACCCCATCGGCGCCGGCGCCCTGTACGACTACGGCCG CTGGCTGGTGGTGGTGACCGGCTGGACCCTGTTCGTGGGCGTGTACATC GTGATCGAGATCGCCCGCGGCAACTAAGAGCACTGGGACGCCCACCGC CCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAATTCTGGAACACA AGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAACGAATTCGGTGCT CAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTACCCAAAATGCTCC CCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACAAAAAAGGAATTATT TTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACCCCACCCTCTATT CTGTTTCTTCCTCCTCACATGGGGGTACACATACACAGCTTCCTCTTTTGG TTCCATCCTTACCACCACACCACACGCACACTCCACATGCCCAGCAGAGT GGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCTGCTGTCTGTAGTT CTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACCCCCTTCCTTGTGA CTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCCACACATTCTCAAC CATAGTCCTTCTAACAATACCAATAGCTAGGACCCGGCTGCTGTGCACTG GGACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCAAGCTGGACTGCC A 39 opt_COX10- ATGGCCGCCTCTCCACACACACTGAGTAGCAGACTGCTGACCGGCTGTG ND1- TTGGCGGCTCTGTGTGGTATCTGGAACGGCGGACAATGCCCATGGCCAA 3'UTR CCTCCTACTCCTCATTGTACCCATTCTAATCGCAATGGCATTCCTAATGCT TACCGAACGAAAAATTCTAGGCTATATGCAACTACGCAAAGGCCCCAACG TTGTAGGCCCCTACGGGCTACTACAACCCTTCGCTGACGCCATGAAACTC TTCACCAAAGAGCCCCTAAAACCCGCCACATCTACCATCACCCTCTACAT CACCGCCCCGACCTTAGCTCTCACCATCGCTCTTCTACTATGGACCCCCC TCCCCATGCCCAACCCCCTGGTCAACCTCAACCTAGGCCTCCTATTTATT CTAGCCACCTCTAGCCTAGCCGTTTACTCAATCCTCTGGTCAGGGTGGGC ATCAAACTCAAACTACGCCCTGATCGGCGCACTGCGAGCAGTAGCCCAA ACAATCTCATATGAAGTCACCCTAGCCATCATTCTACTATCAACATTACTA ATGAGTGGCTCCTTTAACCTCTCCACCCTTATCACAACACAAGAACACCTC TGGTTACTCCTGCCATCATGGCCCTTGGCCATGATGTGGTTTATCTCCAC ACTAGCAGAGACCAACCGAACCCCCTTCGACCTTGCCGAAGGGGAGTCC GAACTAGTCTCAGGCTTCAACATCGAATACGCCGCAGGCCCCTTCGCCCT ATTCTTCATGGCCGAATACACAAACATTATTATGATGAACACCCTCACCAC TACAATCTTCCTAGGAACAACATATGACGCACTCTCCCCTGAACTCTACAC AACATATTTTGTCACCAAGACCCTACTTCTAACCTCCCTGTTCTTATGGAT TCGAACAGCATACCCCCGATTCCGCTACGACCAACTCATGCACCTCCTAT GGAAAAACTTCCTACCACTCACCCTAGCATTACTTATGTGGTATGTCTCCA TGCCCATTACAATCTCCAGCATTCCCCCTCAAACCTAAGAGCACTGGGAC GCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAATT CTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAACGA AAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACAAAAA AGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACCCC ACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACACAGCTT CCTCTTTTGGTTCCATCCTTACCACCACACCACACGCACACTCCACATGC CCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCTGC TGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACCCC CTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCCAC ACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCGGCT GCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCAA GCTGGACTGCCAGCCCCTGTCCTCCCTTCACCCCCATTGCGTATGAGCAT TTCAGAACTCCAAGGAGTCACAGGCATCTTTATAGTTCACGTTAACATATA GACACTGTTGGAAGCAGTTCCTTCTAAAAGGGTAGCCCTGGACTTAATAC CAGCCGGATACCTCTGGCCCCCACCCCATTACTGTACCTCTGGAGTCACT ACTGTGGGTCGCCACTCCTCTGCTACACAGCACGGCTTTTTCAAGGCTGT ATTGAGAAGGGAAGTTAGGAAGAAGGGTGTGCTGGGCTAACCAGCCCAC AGAGCTCACATTCCTGTCCCTTGGGTGAAAAATACATGTCCATCCTGATAT CTCCTGAATTCAGAAATTAGCCTCCACATGTGCAATGGCTTTAAGAGCCA GAAGCAGGGTTCTGGGAATTTTGCAAGTTACCTGTGGCCAGGTGTGGTCT CGGTTACCAAATACGGTTACCTGCAGCTTTTTAGTCCTTTGTGCTCCCAC GGGTCTACAGAGTCCCATCTGCCCAAAGGTCTTGAAGCTTGACAGGATGT TTTCGATTACTCAGTCTCCCAGGGCACTACTGGTCCGTAGGATTCGATTG GTCGGGGTAGGAGAGTTAAACAACATTTAAACAGAGTTCTCTCAAAAATG TCTAAAGGGATTGTAGGTAGATAACATCCAATCACTGTTTGCACTTATCTG AAATCTTCCCTCTTGGCTGCCCCCAGGTATTTACTGTGGAGAACATTGCA TAGGAATGTCTGGAAAAAGCTTCTACAACTTGTTACAGCCTTCACATTTGT AGAAGCTTT 40 opt_COX10- ATGGCCGCCTCTCCACACACACTGAGTAGCAGACTGCTGACCGGCTGTG ND1- TTGGCGGCTCTGTGTGGTATCTGGAACGGCGGACAATGCCCATGGCCAA 3'UTR* CCTCCTACTCCTCATTGTACCCATTCTAATCGCAATGGCATTCCTAATGCT TACCGAACGAAAAATTCTAGGCTATATGCAACTACGCAAAGGCCCCAACG TTGTAGGCCCCTACGGGCTACTACAACCCTTCGCTGACGCCATGAAACTC TTCACCAAAGAGCCCCTAAAACCCGCCACATCTACCATCACCCTCTACAT CACCGCCCCGACCTTAGCTCTCACCATCGCTCTTCTACTATGGACCCCCC TCCCCATGCCCAACCCCCTGGTCAACCTCAACCTAGGCCTCCTATTTATT CTAGCCACCTCTAGCCTAGCCGTTTACTCAATCCTCTGGTCAGGGTGGGC ATCAAACTCAAACTACGCCCTGATCGGCGCACTGCGAGCAGTAGCCCAA ACAATCTCATATGAAGTCACCCTAGCCATCATTCTACTATCAACATTACTA ATGAGTGGCTCCTTTAACCTCTCCACCCTTATCACAACACAAGAACACCTC TGGTTACTCCTGCCATCATGGCCCTTGGCCATGATGTGGTTTATCTCCAC ACTAGCAGAGACCAACCGAACCCCCTTCGACCTTGCCGAAGGGGAGTCC GAACTAGTCTCAGGCTTCAACATCGAATACGCCGCAGGCCCCTTCGCCCT ATTCTTCATGGCCGAATACACAAACATTATTATGATGAACACCCTCACCAC TACAATCTTCCTAGGAACAACATATGACGCACTCTCCCCTGAACTCTACAC AACATATTTTGTCACCAAGACCCTACTTCTAACCTCCCTGTTCTTATGGAT TCGAACAGCATACCCCCGATTCCGCTACGACCAACTCATGCACCTCCTAT GGAAAAACTTCCTACCACTCACCCTAGCATTACTTATGTGGTATGTCTCCA TGCCCATTACAATCTCCAGCATTCCCCCTCAAACCTAAGAGCACTGGGAC GCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAATT CTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAACGA ATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTACCC AAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACAAAAA AGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACCCC ACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACACAGCTT CCTCTTTTGGTTCCATCCTTACCACCACACCACACGCACACTCCACATGC CCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCTGC TGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACCCC CTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCCAC ACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCGGCT GCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCAA GCTGGACTGCCA 41 opt_COX10- ATGGCCGCCTCTCCACACACACTGAGTAGCAGACTGCTGACCGGCTGTG opt_ND1- TTGGCGGCTCTGTGTGGTATCTGGAACGGCGGACAATGCCCATGGCCAA 3'UTR CCTGCTGCTGCTGATCGTGCCCATCCTGATCGCCATGGCCTTCCTGATGC TGACCGAGCGCAAGATCCTGGGCTACATGCAGCTGCGCAAGGGCCCCAA CGTGGTGGGCCCCTACGGCCTGCTGCAGCCCTTCGCCGACGCCATGAA GCTGTTCACCAAGGAGCCCCTGAAGCCCGCCACCAGCACCATCACCCTG TACATCACCGCCCCCACCCTGGCCCTGACCATCGCCCTGCTGCTGTGGA CCCCCCTGCCCATGCCCAACCCCCTGGTGAACCTGAACCTGGGCCTGCT GTTCATCCTGGCCACCAGCAGCCTGGCCGTGTACAGCATCCTGTGGAGC GGCTGGGCCAGCAACAGCAACTACGCCCTGATCGGCGCCCTGCGCGCC GTGGCCCAGACCATCAGCTACGAGGTGACCCTGGCCATCATCCTGCTGA GCACCCTGCTGATGAGCGGCAGCTTCAACCTGAGCACCCTGATCACCAC CCAGGAGCACCTGTGGCTGCTGCTGCCCAGCTGGCCCCTGGCCATGATG TGGTTCATCAGCACCCTGGCCGAGACCAACCGCACCCCCTTCGACCTGG CCGAGGGCGAGAGCGAGCTGGTGAGCGGCTTCAACATCGAGTACGCCG CCGGCCCCTTCGCCCTGTTCTTCATGGCCGAGTACACCAACATCATCATG ATGAACACCCTGACCACCACCATCTTCCTGGGCACCACCTACGACGCCCT GAGCCCCGAGCTGTACACCACCTACTTCGTGACCAAGACCCTGCTGCTG ACCAGCCTGTTCCTGTGGATCCGCACCGCCTACCCCCGCTTCCGCTACG ACCAGCTGATGCACCTGCTGTGGAAGAACTTCCTGCCCCTGACCCTGGC CCTGCTGATGTGGTACGTGAGCATGCCCATCACCATCAGCAGCATCCCC CCCCAGACCTAAGAGCACTGGGACGCCCACCGCCCCTTTCCCTCCGCTG CCAGGCGAGCATGTTGTGGTAATTCTGGAACACAAGAAGAGAAATTGCTG GGTTTAGAACAAGATTATAAACGAATTCGGTGCTCAGTGATCACTTGACA GTTTTTTTTTTTTTTAAATATTACCCAAAATGCTCCCCAAATAAGAAATGCA TCAGCTCAGTCAGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGGTC TTTTATACATCTCTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCTCA CATGGGGGTACACATACACAGCTTCCTCTTTTGGTTCCATCCTTACCACC ACACCACACGCACACTCCACATGCCCAGCAGAGTGGCACTTGGTGGCCA GAAAGTGTGAGCCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGGTC CCTCAAAGGCCTCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCCTG CATTTTTGGTTTTCCCCACCCCACACATTCTCAACCATAGTCCTTCTAACA ATACCAATAGCTAGGACCCGGCTGCTGTGCACTGGGACTGGGGATTCCA CATGTTTGCCTTGGGAGTCTCAAGCTGGACTGCCAGCCCCTGTCCTCCCT TCACCCCCATTGCGTATGAGCATTTCAGAACTCCAAGGAGTCACAGGCAT CTTTATAGTTCACGTTAACATATAGACACTGTTGGAAGCAGTTCCTTCTAA AAGGGTAGCCCTGGACTTAATACCAGCCGGATACCTCTGGCCCCCACCC CATTACTGTACCTCTGGAGTCACTACTGTGGGTCGCCACTCCTCTGCTAC ACAGCACGGCTTTTTCAAGGCTGTATTGAGAAGGGAAGTTAGGAAGAAGG GTGTGCTGGGCTAACCAGCCCACAGAGCTCACATTCCTGTCCCTTGGGT GAAAAATACATGTCCATCCTGATATCTCCTGAATTCAGAAATTAGCCTCCA CATGTGCAATGGCTTTAAGAGCCAGAAGCAGGGTTCTGGGAATTTTGCAA GTTACCTGTGGCCAGGTGTGGTCTCGGTTACCAAATACGGTTACCTGCAG CTTTTTAGTCCTTTGTGCTCCCACGGGTCTACAGAGTCCCATCTGCCCAA AGGTCTTGAAGCTTGACAGGATGTTTTCGATTACTCAGTCTCCCAGGGCA CTACTGGTCCGTAGGATTCGATTGGTCGGGGTAGGAGAGTTAAACAACAT TTAAACAGAGTTCTCTCAAAAATGTCTAAAGGGATTGTAGGTAGATAACAT CCAATCACTGTTTGCACTTATCTGAAATCTTCCCTCTTGGCTGCCCCCAG GTATTTACTGTGGAGAACATTGCATAGGAATGTCTGGAAAAAGCTTCTACA ACTTGTTACAGCCTTCACATTTGTAGAAGCTTT 42 opt_COX10- ATGGCCGCCTCTCCACACACACTGAGTAGCAGACTGCTGACCGGCTGTG opt_ND1- TTGGCGGCTCTGTGTGGTATCTGGAACGGCGGACAATGCCCATGGCCAA 3'UTR* CCTGCTGCTGCTGATCGTGCCCATCCTGATCGCCATGGCCTTCCTGATGC TGACCGAGCGCAAGATCCTGGGCTACATGCAGCTGCGCAAGGGCCCCAA CGTGGTGGGCCCCTACGGCCTGCTGCAGCCCTTCGCCGACGCCATGAA GCTGTTCACCAAGGAGCCCCTGAAGCCCGCCACCAGCACCATCACCCTG TACATCACCGCCCCCACCCTGGCCCTGACCATCGCCCTGCTGCTGTGGA CCCCCCTGCCCATGCCCAACCCCCTGGTGAACCTGAACCTGGGCCTGCT GTTCATCCTGGCCACCAGCAGCCTGGCCGTGTACAGCATCCTGTGGAGC GGCTGGGCCAGCAACAGCAACTACGCCCTGATCGGCGCCCTGCGCGCC GTGGCCCAGACCATCAGCTACGAGGTGACCCTGGCCATCATCCTGCTGA GCACCCTGCTGATGAGCGGCAGCTTCAACCTGAGCACCCTGATCACCAC CCAGGAGCACCTGTGGCTGCTGCTGCCCAGCTGGCCCCTGGCCATGATG TGGTTCATCAGCACCCTGGCCGAGACCAACCGCACCCCCTTCGACCTGG CCGAGGGCGAGAGCGAGCTGGTGAGCGGCTTCAACATCGAGTACGCCG CCGGCCCCTTCGCCCTGTTCTTCATGGCCGAGTACACCAACATCATCATG ATGAACACCCTGACCACCACCATCTTCCTGGGCACCACCTACGACGCCCT GAGCCCCGAGCTGTACACCACCTACTTCGTGACCAAGACCCTGCTGCTG ACCAGCCTGTTCCTGTGGATCCGCACCGCCTACCCCCGCTTCCGCTACG ACCAGCTGATGCACCTGCTGTGGAAGAACTTCCTGCCCCTGACCCTGGC CCTGCTGATGTGGTACGTGAGCATGCCCATCACCATCAGCAGCATCCCC CCCCAGACCTAAGAGCACTGGGACGCCCACCGCCCCTTTCCCTCCGCTG CCAGGCGAGCATGTTGTGGTAATTCTGGAACACAAGAAGAGAAATTGCTG GGTTTAGAACAAGATTATAAACGAATTCGGTGCTCAGTGATCACTTGACA GTTTTTTTTTTTTTTAAATATTACCCAAAATGCTCCCCAAATAAGAAATGCA TCAGCTCAGTCAGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGGTC TTTTATACATCTCTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCTCA CATGGGGGTACACATACACAGCTTCCTCTTTTGGTTCCATCCTTACCACC ACACCACACGCACACTCCACATGCCCAGCAGAGTGGCACTTGGTGGCCA GAAAGTGTGAGCCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGGTC CCTCAAAGGCCTCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCCTG CATTTTTGGTTTTCCCCACCCCACACATTCTCAACCATAGTCCTTCTAACA ATACCAATAGCTAGGACCCGGCTGCTGTGCACTGGGACTGGGGATTCCA CATGTTTGCCTTGGGAGTCTCAAGCTGGACTGCCA 43 opt_COX10*- ATGGCCGCCAGCCCCCACACCCTGAGCAGCCGCCTGCTGACCGGCTGC ND4- GTGGGCGGCAGCGTGTGGTACCTGGAGCGCCGCACCATGCTAAAACTAA 3'UTR TCGTCCCAACAATTATGTTACTACCACTGACATGGCTTTCCAAAAAACACA TGATTTGGATCAACACAACCACCCACAGCCTAATTATTAGCATCATCCCTC TACTATTTTTTAACCAAATCAACAACAACCTATTTAGCTGTTCCCCAACCTT TTCCTCCGACCCCCTAACAACCCCCCTCCTAATGCTAACTACCTGGCTCC TACCCCTCACAATCATGGCAAGCCAACGCCACTTATCCAGTGAACCACTA TCACGAAAAAAACTCTACCTCTCTATGCTAATCTCCCTACAAATCTCCTTA ATTATGACATTCACAGCCACAGAACTAATCATGTTTTATATCTTCTTCGAAA CCACACTTATCCCCACCTTGGCTATCATCACCCGATGGGGCAACCAGCCA GAACGCCTGAACGCAGGCACATACTTCCTATTCTACACCCTAGTAGGCTC CCTTCCCCTACTCATCGCACTAATTTACACTCACAACACCCTAGGCTCACT AAACATTCTACTACTCACTCTCACTGCCCAAGAACTATCAAACTCCTGGGC CAACAACTTAATGTGGCTAGCTTACACAATGGCTTTTATGGTAAAGATGCC TCTTTACGGACTCCACTTATGGCTCCCTAAAGCCCATGTCGAAGCCCCCA TCGCTGGGTCAATGGTACTTGCCGCAGTACTCTTAAAACTAGGCGGCTAT GGTATGATGCGCCTCACACTCATTCTCAACCCCCTGACAAAACACATGGC CTACCCCTTCCTTGTACTATCCCTATGGGGCATGATTATGACAAGCTCCAT CTGCCTACGACAAACAGACCTAAAATCGCTCATTGCATACTCTTCAATCAG CCACATGGCCCTCGTAGTAACAGCCATTCTCATCCAAACCCCCTGGAGCT TCACCGGCGCAGTCATTCTCATGATCGCCCACGGGCTTACATCCTCATTA CTATTCTGCCTAGCAAACTCAAACTACGAACGCACTCACAGTCGCATCAT GATCCTCTCTCAAGGACTTCAAACTCTACTCCCACTAATGGCTTTTTGGTG GCTTCTAGCAAGCCTCGCTAACCTCGCCTTACCCCCCACTATTAACCTAC TGGGAGAACTCTCTGTGCTAGTAACCACGTTCTCCTGGTCAAATATCACT CTCCTACTTACAGGACTCAACATGCTAGTCACAGCCCTATACTCCCTCTAC ATGTTTACCACAACACAATGGGGCTCACTCACCCACCACATTAACAACAT GAAACCCTCATTCACACGAGAAAACACCCTCATGTTCATGCACCTATCCC CCATTCTCCTCCTATCCCTCAACCCCGACATCATTACCGGGTTTTCCTCTT AAGAGCACTGGGACGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAG CATGTTGTGGTAATTCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAA CAAGATTATAAACGAATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTT TTTTAAATATTACCCAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGT CAGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATC TCTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTA CACATACACAGCTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGC ACACTCCACATGCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAG CCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCC TCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTT TCCCCACCCCACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCT AGGACCCGGCTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTT GGGAGTCTCAAGCTGGACTGCCAGCCCCTGTCCTCCCTTCACCCCCATT GCGTATGAGCATTTCAGAACTCCAAGGAGTCACAGGCATCTTTATAGTTC ACGTTAACATATAGACACTGTTGGAAGCAGTTCCTTCTAAAAGGGTAGCC CTGGACTTAATACCAGCCGGATACCTCTGGCCCCCACCCCATTACTGTAC CTCTGGAGTCACTACTGTGGGTCGCCACTCCTCTGCTACACAGCACGGC TTTTTCAAGGCTGTATTGAGAAGGGAAGTTAGGAAGAAGGGTGTGCTGGG CTAACCAGCCCACAGAGCTCACATTCCTGTCCCTTGGGTGAAAAATACAT GTCCATCCTGATATCTCCTGAATTCAGAAATTAGCCTCCACATGTGCAATG
GCTTTAAGAGCCAGAAGCAGGGTTCTGGGAATTTTGCAAGTTACCTGTGG CCAGGTGTGGTCTCGGTTACCAAATACGGTTACCTGCAGCTTTTTAGTCC TTTGTGCTCCCACGGGTCTACAGAGTCCCATCTGCCCAAAGGTCTTGAAG CTTGACAGGATGTTTTCGATTACTCAGTCTCCCAGGGCACTACTGGTCCG TAGGATTCGATTGGTCGGGGTAGGAGAGTTAAACAACATTTAAACAGAGT TCTCTCAAAAATGTCTAAAGGGATTGTAGGTAGATAACATCCAATCACTGT TTGCACTTATCTGAAATCTTCCCTCTTGGCTGCCCCCAGGTATTTACTGTG GAGAACATTGCATAGGAATGTCTGGAAAAAGCTTCTACAACTTGTTACAG CCTTCACATTTGTAGAAGCTTT 44 opt_COX10*- ATGGCCGCCAGCCCCCACACCCTGAGCAGCCGCCTGCTGACCGGCTGC ND4- GTGGGCGGCAGCGTGTGGTACCTGGAGCGCCGCACCATGCTAAAACTAA 3'UTR* TCGTCCCAACAATTATGTTACTACCACTGACATGGCTTTCCAAAAAACACA TGATTTGGATCAACACAACCACCCACAGCCTAATTATTAGCATCATCCCTC TACTATTTTTTAACCAAATCAACAACAACCTATTTAGCTGTTCCCCAACCTT TTCCTCCGACCCCCTAACAACCCCCCTCCTAATGCTAACTACCTGGCTCC TACCCCTCACAATCATGGCAAGCCAACGCCACTTATCCAGTGAACCACTA TCACGAAAAAAACTCTACCTCTCTATGCTAATCTCCCTACAAATCTCCTTA ATTATGACATTCACAGCCACAGAACTAATCATGTTTTATATCTTCTTCGAAA CCACACTTATCCCCACCTTGGCTATCATCACCCGATGGGGCAACCAGCCA GAACGCCTGAACGCAGGCACATACTTCCTATTCTACACCCTAGTAGGCTC CCTTCCCCTACTCATCGCACTAATTTACACTCACAACACCCTAGGCTCACT AAACATTCTACTACTCACTCTCACTGCCCAAGAACTATCAAACTCCTGGGC CAACAACTTAATGTGGCTAGCTTACACAATGGCTTTTATGGTAAAGATGCC TCTTTACGGACTCCACTTATGGCTCCCTAAAGCCCATGTCGAAGCCCCCA TCGCTGGGTCAATGGTACTTGCCGCAGTACTCTTAAAACTAGGCGGCTAT GGTATGATGCGCCTCACACTCATTCTCAACCCCCTGACAAAACACATGGC CTACCCCTTCCTTGTACTATCCCTATGGGGCATGATTATGACAAGCTCCAT CTGCCTACGACAAACAGACCTAAAATCGCTCATTGCATACTCTTCAATCAG CCACATGGCCCTCGTAGTAACAGCCATTCTCATCCAAACCCCCTGGAGCT TCACCGGCGCAGTCATTCTCATGATCGCCCACGGGCTTACATCCTCATTA CTATTCTGCCTAGCAAACTCAAACTACGAACGCACTCACAGTCGCATCAT GATCCTCTCTCAAGGACTTCAAACTCTACTCCCACTAATGGCTTTTTGGTG GCTTCTAGCAAGCCTCGCTAACCTCGCCTTACCCCCCACTATTAACCTAC TGGGAGAACTCTCTGTGCTAGTAACCACGTTCTCCTGGTCAAATATCACT CTCCTACTTACAGGACTCAACATGCTAGTCACAGCCCTATACTCCCTCTAC ATGTTTACCACAACACAATGGGGCTCACTCACCCACCACATTAACAACAT GAAACCCTCATTCACACGAGAAAACACCCTCATGTTCATGCACCTATCCC CCATTCTCCTCCTATCCCTCAACCCCGACATCATTACCGGGTTTTCCTCTT AAGAGCACTGGGACGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAG CATGTTGTGGTAATTCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAA CAAGATTATAAACGAATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTT TTTTAAATATTACCCAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGT CAGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATC TCTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTA CACATACACAGCTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGC ACACTCCACATGCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAG CCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCC TCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTT TCCCCACCCCACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCT AGGACCCGGCTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTT GGGAGTCTCAAGCTGGACTGCCA 45 opt_COX10*- ATGGCCGCCAGCCCCCACACCCTGAGCAGCCGCCTGCTGACCGGCTGC opt_ND4- GTGGGCGGCAGCGTGTGGTACCTGGAGCGCCGCACCATGCTGAAGCTG 3'UTR ATCGTGCCCACCATCATGCTGCTGCCTCTGACCTGGCTGAGCAAGAAACA CATGATCTGGATCAACACCACCACGCACAGCCTGATCATCAGCATCATCC CTCTGCTGTTCTTCAACCAGATCAACAACAACCTGTTCAGCTGCAGCCCC ACCTTCAGCAGCGACCCTCTGACAACACCTCTGCTGATGCTGACCACCTG GCTGCTGCCCCTCACAATCATGGCCTCTCAGAGACACCTGAGCAGCGAG CCCCTGAGCCGGAAGAAACTGTACCTGAGCATGCTGATCTCCCTGCAGA TCTCTCTGATCATGACCTTCACCGCCACCGAGCTGATCATGTTCTACATCT TTTTCGAGACAACGCTGATCCCCACACTGGCCATCATCACCAGATGGGGC AACCAGCCTGAGAGACTGAACGCCGGCACCTACTTTCTGTTCTACACCCT CGTGGGCAGCCTGCCACTGCTGATTGCCCTGATCTACACCCACAACACC CTGGGCTCCCTGAACATCCTGCTGCTGACACTGACAGCCCAAGAGCTGA GCAACAGCTGGGCCAACAATCTGATGTGGCTGGCCTACACAATGGCCTT CATGGTCAAGATGCCCCTGTACGGCCTGCACCTGTGGCTGCCTAAAGCT CATGTGGAAGCCCCTATCGCCGGCTCTATGGTGCTGGCTGCAGTGCTGC TGAAACTCGGCGGCTACGGCATGATGCGGCTGACCCTGATTCTGAATCC CCTGACCAAGCACATGGCCTATCCATTTCTGGTGCTGAGCCTGTGGGGC ATGATTATGACCAGCAGCATCTGCCTGCGGCAGACCGATCTGAAGTCCCT GATCGCCTACAGCTCCATCAGCCACATGGCCCTGGTGGTCACCGCCATC CTGATTCAGACCCCTTGGAGCTTTACAGGCGCCGTGATCCTGATGATTGC CCACGGCCTGACAAGCAGCCTGCTGTTTTGTCTGGCCAACAGCAACTAC GAGCGGACCCACAGCAGAATCATGATCCTGTCTCAGGGCCTGCAGACCC TCCTGCCTCTTATGGCTTTTTGGTGGCTGCTGGCCTCTCTGGCCAATCTG GCACTGCCTCCTACCATCAATCTGCTGGGCGAGCTGAGCGTGCTGGTCA CCACATTCAGCTGGTCCAATATCACCCTGCTGCTCACCGGCCTGAACATG CTGGTTACAGCCCTGTACTCCCTGTACATGTTCACCACCACACAGTGGGG AAGCCTGACACACCACATCAACAATATGAAGCCCAGCTTCACCCGCGAGA ACACCCTGATGTTCATGCATCTGAGCCCCATTCTGCTGCTGTCCCTGAAT CCTGATATCATCACCGGCTTCTCCAGCTGAGAGCACTGGGACGCCCACC GCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAATTCTGGAACA CAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAACGAATTCGGTG CTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTACCCAAAATGCT CCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACAAAAAAGGAATT ATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACCCCACCCTCT ATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACACAGCTTCCTCTTT TGGTTCCATCCTTACCACCACACCACACGCACACTCCACATGCCCAGCAG AGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCTGCTGTCTGTA GTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACCCCCTTCCTTGT GACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCCACACATTCTCA ACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCGGCTGCTGTGCAC TGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCAAGCTGGACTG CCAGCCCCTGTCCTCCCTTCACCCCCATTGCGTATGAGCATTTCAGAACT CCAAGGAGTCACAGGCATCTTTATAGTTCACGTTAACATATAGACACTGTT GGAAGCAGTTCCTTCTAAAAGGGTAGCCCTGGACTTAATACCAGCCGGAT ACCTCTGGCCCCCACCCCATTACTGTACCTCTGGAGTCACTACTGTGGGT CGCCACTCCTCTGCTACACAGCACGGCTTTTTCAAGGCTGTATTGAGAAG GGAAGTTAGGAAGAAGGGTGTGCTGGGCTAACCAGCCCACAGAGCTCAC ATTCCTGTCCCTTGGGTGAAAAATACATGTCCATCCTGATATCTCCTGAAT TCAGAAATTAGCCTCCACATGTGCAATGGCTTTAAGAGCCAGAAGCAGGG TTCTGGGAATTTTGCAAGTTACCTGTGGCCAGGTGTGGTCTCGGTTACCA AATACGGTTACCTGCAGCTTTTTAGTCCTTTGTGCTCCCACGGGTCTACA GAGTCCCATCTGCCCAAAGGTCTTGAAGCTTGACAGGATGTTTTCGATTA CTCAGTCTCCCAGGGCACTACTGGTCCGTAGGATTCGATTGGTCGGGGT AGGAGAGTTAAACAACATTTAAACAGAGTTCTCTCAAAAATGTCTAAAGGG ATTGTAGGTAGATAACATCCAATCACTGTTTGCACTTATCTGAAATCTTCC CTCTTGGCTGCCCCCAGGTATTTACTGTGGAGAACATTGCATAGGAATGT CTGGAAAAAGCTTCTACAACTTGTTACAGCCTTCACATTTGTAGAAGCTTT 46 opt_COX10*- ATGGCCGCCAGCCCCCACACCCTGAGCAGCCGCCTGCTGACCGGCTGC opt_ND4- GTGGGCGGCAGCGTGTGGTACCTGGAGCGCCGCACCATGCTGAAGCTG 3'UTR* ATCGTGCCCACCATCATGCTGCTGCCTCTGACCTGGCTGAGCAAGAAACA CATGATCTGGATCAACACCACCACGCACAGCCTGATCATCAGCATCATCC CTCTGCTGTTCTTCAACCAGATCAACAACAACCTGTTCAGCTGCAGCCCC ACCTTCAGCAGCGACCCTCTGACAACACCTCTGCTGATGCTGACCACCTG GCTGCTGCCCCTCACAATCATGGCCTCTCAGAGACACCTGAGCAGCGAG CCCCTGAGCCGGAAGAAACTGTACCTGAGCATGCTGATCTCCCTGCAGA TCTCTCTGATCATGACCTTCACCGCCACCGAGCTGATCATGTTCTACATCT TTTTCGAGACAACGCTGATCCCCACACTGGCCATCATCACCAGATGGGGC AACCAGCCTGAGAGACTGAACGCCGGCACCTACTTTCTGTTCTACACCCT CGTGGGCAGCCTGCCACTGCTGATTGCCCTGATCTACACCCACAACACC CTGGGCTCCCTGAACATCCTGCTGCTGACACTGACAGCCCAAGAGCTGA GCAACAGCTGGGCCAACAATCTGATGTGGCTGGCCTACACAATGGCCTT CATGGTCAAGATGCCCCTGTACGGCCTGCACCTGTGGCTGCCTAAAGCT CATGTGGAAGCCCCTATCGCCGGCTCTATGGTGCTGGCTGCAGTGCTGC TGAAACTCGGCGGCTACGGCATGATGCGGCTGACCCTGATTCTGAATCC CCTGACCAAGCACATGGCCTATCCATTTCTGGTGCTGAGCCTGTGGGGC ATGATTATGACCAGCAGCATCTGCCTGCGGCAGACCGATCTGAAGTCCCT GATCGCCTACAGCTCCATCAGCCACATGGCCCTGGTGGTCACCGCCATC CTGATTCAGACCCCTTGGAGCTTTACAGGCGCCGTGATCCTGATGATTGC CCACGGCCTGACAAGCAGCCTGCTGTTTTGTCTGGCCAACAGCAACTAC GAGCGGACCCACAGCAGAATCATGATCCTGTCTCAGGGCCTGCAGACCC TCCTGCCTCTTATGGCTTTTTGGTGGCTGCTGGCCTCTCTGGCCAATCTG GCACTGCCTCCTACCATCAATCTGCTGGGCGAGCTGAGCGTGCTGGTCA CCACATTCAGCTGGTCCAATATCACCCTGCTGCTCACCGGCCTGAACATG CTGGTTACAGCCCTGTACTCCCTGTACATGTTCACCACCACACAGTGGGG AAGCCTGACACACCACATCAACAATATGAAGCCCAGCTTCACCCGCGAGA ACACCCTGATGTTCATGCATCTGAGCCCCATTCTGCTGCTGTCCCTGAAT CCTGATATCATCACCGGCTTCTCCAGCTGAGAGCACTGGGACGCCCACC GCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAATTCTGGAACA CAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAACGAATTCGGTG CTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTACCCAAAATGCT CCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACAAAAAAGGAATT ATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACCCCACCCTCT ATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACACAGCTTCCTCTTT TGGTTCCATCCTTACCACCACACCACACGCACACTCCACATGCCCAGCAG AGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCTGCTGTCTGTA GTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACCCCCTTCCTTGT GACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCCACACATTCTCA ACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCGGCTGCTGTGCAC TGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCAAGCTGGACTG CCA 47 opt_COX10*- ATGGCCGCCAGCCCCCACACCCTGAGCAGCCGCCTGCTGACCGGCTGC opt_ND4*- GTGGGCGGCAGCGTGTGGTACCTGGAGCGCCGCACCATGCTGAAGCTG 3'UTR ATCGTGCCCACCATCATGCTGCTGCCCCTGACCTGGCTGAGCAAGAAGC ACATGATCTGGATCAACACCACCACCCACAGCCTGATCATCAGCATCATC CCCCTGCTGTTCTTCAACCAGATCAACAACAACCTGTTCAGCTGCAGCCC CACCTTCAGCAGCGACCCCCTGACCACCCCCCTGCTGATGCTGACCACC TGGCTGCTGCCCCTGACCATCATGGCCAGCCAGCGCCACCTGAGCAGCG AGCCCCTGAGCCGCAAGAAGCTGTACCTGAGCATGCTGATCAGCCTGCA GATCAGCCTGATCATGACCTTCACCGCCACCGAGCTGATCATGTTCTACA TCTTCTTCGAGACCACCCTGATCCCCACCCTGGCCATCATCACCCGCTGG GGCAACCAGCCCGAGCGCCTGAACGCCGGCACCTACTTCCTGTTCTACA CCCTGGTGGGCAGCCTGCCCCTGCTGATCGCCCTGATCTACACCCACAA CACCCTGGGCAGCCTGAACATCCTGCTGCTGACCCTGACCGCCCAGGAG CTGAGCAACAGCTGGGCCAACAACCTGATGTGGCTGGCCTACACCATGG CCTTCATGGTGAAGATGCCCCTGTACGGCCTGCACCTGTGGCTGCCCAA GGCCCACGTGGAGGCCCCCATCGCCGGCAGCATGGTGCTGGCCGCCGT GCTGCTGAAGCTGGGCGGCTACGGCATGATGCGCCTGACCCTGATCCTG AACCCCCTGACCAAGCACATGGCCTACCCCTTCCTGGTGCTGAGCCTGT GGGGCATGATCATGACCAGCAGCATCTGCCTGCGCCAGACCGACCTGAA GAGCCTGATCGCCTACAGCAGCATCAGCCACATGGCCCTGGTGGTGACC GCCATCCTGATCCAGACCCCCTGGAGCTTCACCGGCGCCGTGATCCTGA TGATCGCCCACGGCCTGACCAGCAGCCTGCTGTTCTGCCTGGCCAACAG CAACTACGAGCGCACCCACAGCCGCATCATGATCCTGAGCCAGGGCCTG CAGACCCTGCTGCCCCTGATGGCCTTCTGGTGGCTGCTGGCCAGCCTGG CCAACCTGGCCCTGCCCCCCACCATCAACCTGCTGGGCGAGCTGAGCGT GCTGGTGACCACCTTCAGCTGGAGCAACATCACCCTGCTGCTGACCGGC CTGAACATGCTGGTGACCGCCCTGTACAGCCTGTACATGTTCACCACCAC CCAGTGGGGCAGCCTGACCCACCACATCAACAACATGAAGCCCAGCTTC ACCCGCGAGAACACCCTGATGTTCATGCACCTGAGCCCCATCCTGCTGC TGAGCCTGAACCCCGACATCATCACCGGCTTCAGCAGCTAAGAGCACTG GGACGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGT AATTCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAA CGAATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTA CCCAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACA AAAAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAAC CCCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACACA GCTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGCACACTCCAC ATGCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGAT CTGCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCA CCCCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACC CCACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCG GCTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCT CAAGCTGGACTGCCAGCCCCTGTCCTCCCTTCACCCCCATTGCGTATGA GCATTTCAGAACTCCAAGGAGTCACAGGCATCTTTATAGTTCACGTTAACA TATAGACACTGTTGGAAGCAGTTCCTTCTAAAAGGGTAGCCCTGGACTTA ATACCAGCCGGATACCTCTGGCCCCCACCCCATTACTGTACCTCTGGAGT CACTACTGTGGGTCGCCACTCCTCTGCTACACAGCACGGCTTTTTCAAGG CTGTATTGAGAAGGGAAGTTAGGAAGAAGGGTGTGCTGGGCTAACCAGC CCACAGAGCTCACATTCCTGTCCCTTGGGTGAAAAATACATGTCCATCCT GATATCTCCTGAATTCAGAAATTAGCCTCCACATGTGCAATGGCTTTAAGA GCCAGAAGCAGGGTTCTGGGAATTTTGCAAGTTACCTGTGGCCAGGTGT GGTCTCGGTTACCAAATACGGTTACCTGCAGCTTTTTAGTCCTTTGTGCTC CCACGGGTCTACAGAGTCCCATCTGCCCAAAGGTCTTGAAGCTTGACAG GATGTTTTCGATTACTCAGTCTCCCAGGGCACTACTGGTCCGTAGGATTC GATTGGTCGGGGTAGGAGAGTTAAACAACATTTAAACAGAGTTCTCTCAA AAATGTCTAAAGGGATTGTAGGTAGATAACATCCAATCACTGTTTGCACTT ATCTGAAATCTTCCCTCTTGGCTGCCCCCAGGTATTTACTGTGGAGAACA TTGCATAGGAATGTCTGGAAAAAGCTTCTACAACTTGTTACAGCCTTCACA TTTGTAGAAGCTTT 48 opt_COX10*- ATGGCCGCCAGCCCCCACACCCTGAGCAGCCGCCTGCTGACCGGCTGC opt_ND4*- GTGGGCGGCAGCGTGTGGTACCTGGAGCGCCGCACCATGCTGAAGCTG 3'UTR* ATCGTGCCCACCATCATGCTGCTGCCCCTGACCTGGCTGAGCAAGAAGC ACATGATCTGGATCAACACCACCACCCACAGCCTGATCATCAGCATCATC CCCCTGCTGTTCTTCAACCAGATCAACAACAACCTGTTCAGCTGCAGCCC CACCTTCAGCAGCGACCCCCTGACCACCCCCCTGCTGATGCTGACCACC TGGCTGCTGCCCCTGACCATCATGGCCAGCCAGCGCCACCTGAGCAGCG AGCCCCTGAGCCGCAAGAAGCTGTACCTGAGCATGCTGATCAGCCTGCA GATCAGCCTGATCATGACCTTCACCGCCACCGAGCTGATCATGTTCTACA TCTTCTTCGAGACCACCCTGATCCCCACCCTGGCCATCATCACCCGCTGG GGCAACCAGCCCGAGCGCCTGAACGCCGGCACCTACTTCCTGTTCTACA CCCTGGTGGGCAGCCTGCCCCTGCTGATCGCCCTGATCTACACCCACAA CACCCTGGGCAGCCTGAACATCCTGCTGCTGACCCTGACCGCCCAGGAG CTGAGCAACAGCTGGGCCAACAACCTGATGTGGCTGGCCTACACCATGG CCTTCATGGTGAAGATGCCCCTGTACGGCCTGCACCTGTGGCTGCCCAA GGCCCACGTGGAGGCCCCCATCGCCGGCAGCATGGTGCTGGCCGCCGT GCTGCTGAAGCTGGGCGGCTACGGCATGATGCGCCTGACCCTGATCCTG AACCCCCTGACCAAGCACATGGCCTACCCCTTCCTGGTGCTGAGCCTGT GGGGCATGATCATGACCAGCAGCATCTGCCTGCGCCAGACCGACCTGAA GAGCCTGATCGCCTACAGCAGCATCAGCCACATGGCCCTGGTGGTGACC GCCATCCTGATCCAGACCCCCTGGAGCTTCACCGGCGCCGTGATCCTGA TGATCGCCCACGGCCTGACCAGCAGCCTGCTGTTCTGCCTGGCCAACAG CAACTACGAGCGCACCCACAGCCGCATCATGATCCTGAGCCAGGGCCTG CAGACCCTGCTGCCCCTGATGGCCTTCTGGTGGCTGCTGGCCAGCCTGG CCAACCTGGCCCTGCCCCCCACCATCAACCTGCTGGGCGAGCTGAGCGT GCTGGTGACCACCTTCAGCTGGAGCAACATCACCCTGCTGCTGACCGGC CTGAACATGCTGGTGACCGCCCTGTACAGCCTGTACATGTTCACCACCAC CCAGTGGGGCAGCCTGACCCACCACATCAACAACATGAAGCCCAGCTTC ACCCGCGAGAACACCCTGATGTTCATGCACCTGAGCCCCATCCTGCTGC TGAGCCTGAACCCCGACATCATCACCGGCTTCAGCAGCTAAGAGCACTG GGACGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGT AATTCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAA CGAATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTA CCCAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACA AAAAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAAC
CCCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACACA GCTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGCACACTCCAC ATGCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGAT CTGCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCA CCCCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACC CCACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCG GCTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCT CAAGCTGGACTGCCA 49 opt_COX10*- ATGGCCGCCAGCCCCCACACCCTGAGCAGCCGCCTGCTGACCGGCTGC ND6- GTGGGCGGCAGCGTGTGGTACCTGGAGCGCCGCACCATGATGTATGCTT 3'UTR TGTTTCTGTTGAGTGTGGGTTTAGTAATGGGGTTTGTGGGGTTTTCTTCTA AGCCTTCTCCTATTTATGGGGGTTTAGTATTGATTGTTAGCGGTGTGGTC GGGTGTGTTATTATTCTGAATTTTGGGGGAGGTTATATGGGTTTAATGGTT TTTTTAATTTATTTAGGGGGAATGATGGTTGTCTTTGGATATACTACAGCG ATGGCTATTGAGGAGTATCCTGAGGCATGGGGGTCAGGGGTTGAGGTCT TGGTGAGTGTTTTAGTGGGGTTAGCGATGGAGGTAGGATTGGTGCTGTG GGTGAAAGAGTATGATGGGGTGGTGGTTGTGGTAAACTTTAATAGTGTAG GAAGCTGGATGATTTATGAAGGAGAGGGGTCAGGGTTGATTCGGGAGGA TCCTATTGGTGCGGGGGCTTTGTATGATTATGGGCGTTGGTTAGTAGTAG TTACTGGTTGGACATTGTTTGTTGGTGTATATATTGTAATTGAGATTGCTC GGGGGAATTAGGAGCACTGGGACGCCCACCGCCCCTTTCCCTCCGCTGC CAGGCGAGCATGTTGTGGTAATTCTGGAACACAAGAAGAGAAATTGCTGG GTTTAGAACAAGATTATAAACGAATTCGGTGCTCAGTGATCACTTGACAGT TTTTTTTTTTTTTAAATATTACCCAAAATGCTCCCCAAATAAGAAATGCATC AGCTCAGTCAGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGGTCTT TTATACATCTCTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCTCAC ATGGGGGTACACATACACAGCTTCCTCTTTTGGTTCCATCCTTACCACCA CACCACACGCACACTCCACATGCCCAGCAGAGTGGCACTTGGTGGCCAG AAAGTGTGAGCCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGGTCC CTCAAAGGCCTCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCCTGC ATTTTTGGTTTTCCCCACCCCACACATTCTCAACCATAGTCCTTCTAACAA TACCAATAGCTAGGACCCGGCTGCTGTGCACTGGGACTGGGGATTCCAC ATGTTTGCCTTGGGAGTCTCAAGCTGGACTGCCAGCCCCTGTCCTCCCTT CACCCCCATTGCGTATGAGCATTTCAGAACTCCAAGGAGTCACAGGCATC TTTATAGTTCACGTTAACATATAGACACTGTTGGAAGCAGTTCCTTCTAAA AGGGTAGCCCTGGACTTAATACCAGCCGGATACCTCTGGCCCCCACCCC ATTACTGTACCTCTGGAGTCACTACTGTGGGTCGCCACTCCTCTGCTACA CAGCACGGCTTTTTCAAGGCTGTATTGAGAAGGGAAGTTAGGAAGAAGG GTGTGCTGGGCTAACCAGCCCACAGAGCTCACATTCCTGTCCCTTGGGT GAAAAATACATGTCCATCCTGATATCTCCTGAATTCAGAAATTAGCCTCCA CATGTGCAATGGCTTTAAGAGCCAGAAGCAGGGTTCTGGGAATTTTGCAA GTTACCTGTGGCCAGGTGTGGTCTCGGTTACCAAATACGGTTACCTGCAG CTTTTTAGTCCTTTGTGCTCCCACGGGTCTACAGAGTCCCATCTGCCCAA AGGTCTTGAAGCTTGACAGGATGTTTTCGATTACTCAGTCTCCCAGGGCA CTACTGGTCCGTAGGATTCGATTGGTCGGGGTAGGAGAGTTAAACAACAT TTAAACAGAGTTCTCTCAAAAATGTCTAAAGGGATTGTAGGTAGATAACAT CCAATCACTGTTTGCACTTATCTGAAATCTTCCCTCTTGGCTGCCCCCAG GTATTTACTGTGGAGAACATTGCATAGGAATGTCTGGAAAAAGCTTCTACA ACTTGTTACAGCCTTCACATTTGTAGAAGCTTT 50 opt_COX10*- ATGGCCGCCAGCCCCCACACCCTGAGCAGCCGCCTGCTGACCGGCTGC ND6- GTGGGCGGCAGCGTGTGGTACCTGGAGCGCCGCACCATGATGTATGCTT 3'UTR* TGTTTCTGTTGAGTGTGGGTTTAGTAATGGGGTTTGTGGGGTTTTCTTCTA AGCCTTCTCCTATTTATGGGGGTTTAGTATTGATTGTTAGCGGTGTGGTC GGGTGTGTTATTATTCTGAATTTTGGGGGAGGTTATATGGGTTTAATGGTT TTTTTAATTTATTTAGGGGGAATGATGGTTGTCTTTGGATATACTACAGCG ATGGCTATTGAGGAGTATCCTGAGGCATGGGGGTCAGGGGTTGAGGTCT TGGTGAGTGTTTTAGTGGGGTTAGCGATGGAGGTAGGATTGGTGCTGTG GGTGAAAGAGTATGATGGGGTGGTGGTTGTGGTAAACTTTAATAGTGTAG GAAGCTGGATGATTTATGAAGGAGAGGGGTCAGGGTTGATTCGGGAGGA TCCTATTGGTGCGGGGGCTTTGTATGATTATGGGCGTTGGTTAGTAGTAG TTACTGGTTGGACATTGTTTGTTGGTGTATATATTGTAATTGAGATTGCTC GGGGGAATTAGGAGCACTGGGACGCCCACCGCCCCTTTCCCTCCGCTGC CAGGCGAGCATGTTGTGGTAATTCTGGAACACAAGAAGAGAAATTGCTGG GTTTAGAACAAGATTATAAACGAATTCGGTGCTCAGTGATCACTTGACAGT TTTTTTTTTTTTTAAATATTACCCAAAATGCTCCCCAAATAAGAAATGCATC AGCTCAGTCAGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGGTCTT TTATACATCTCTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCTCAC ATGGGGGTACACATACACAGCTTCCTCTTTTGGTTCCATCCTTACCACCA CACCACACGCACACTCCACATGCCCAGCAGAGTGGCACTTGGTGGCCAG AAAGTGTGAGCCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGGTCC CTCAAAGGCCTCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCCTGC ATTTTTGGTTTTCCCCACCCCACACATTCTCAACCATAGTCCTTCTAACAA TACCAATAGCTAGGACCCGGCTGCTGTGCACTGGGACTGGGGATTCCAC ATGTTTGCCTTGGGAGTCTCAAGCTGGACTGCCA 51 opt_COX10*- ATGGCCGCCAGCCCCCACACCCTGAGCAGCCGCCTGCTGACCGGCTGC opt_ND6- GTGGGCGGCAGCGTGTGGTACCTGGAGCGCCGCACCATGATGTACGCC 3'UTR CTGTTCCTGCTGAGCGTGGGCCTGGTGATGGGCTTCGTGGGCTTCAGCA GCAAGCCCAGCCCCATCTACGGCGGCCTGGTGCTGATCGTGAGCGGCG TGGTGGGCTGCGTGATCATCCTGAACTTCGGCGGCGGCTACATGGGCCT GATGGTGTTCCTGATCTACCTGGGCGGCATGATGGTGGTGTTCGGCTAC ACCACCGCCATGGCCATCGAGGAGTACCCCGAGGCCTGGGGCAGCGGC GTGGAGGTGCTGGTGAGCGTGCTGGTGGGCCTGGCCATGGAGGTGGGC CTGGTGCTGTGGGTGAAGGAGTACGACGGCGTGGTGGTGGTGGTGAAC TTCAACAGCGTGGGCAGCTGGATGATCTACGAGGGCGAGGGCAGCGGC CTGATCCGCGAGGACCCCATCGGCGCCGGCGCCCTGTACGACTACGGC CGCTGGCTGGTGGTGGTGACCGGCTGGACCCTGTTCGTGGGCGTGTAC ATCGTGATCGAGATCGCCCGCGGCAACTAAGAGCACTGGGACGCCCACC GCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAATTCTGGAACA CAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAACGAATTCGGTG CTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTACCCAAAATGCT CCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACAAAAAAGGAATT ATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACCCCACCCTCT ATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACACAGCTTCCTCTTT TGGTTCCATCCTTACCACCACACCACACGCACACTCCACATGCCCAGCAG AGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCTGCTGTCTGTA GTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACCCCCTTCCTTGT GACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCCACACATTCTCA ACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCGGCTGCTGTGCAC TGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCAAGCTGGACTG CCAGCCCCTGTCCTCCCTTCACCCCCATTGCGTATGAGCATTTCAGAACT CCAAGGAGTCACAGGCATCTTTATAGTTCACGTTAACATATAGACACTGTT GGAAGCAGTTCCTTCTAAAAGGGTAGCCCTGGACTTAATACCAGCCGGAT ACCTCTGGCCCCCACCCCATTACTGTACCTCTGGAGTCACTACTGTGGGT CGCCACTCCTCTGCTACACAGCACGGCTTTTTCAAGGCTGTATTGAGAAG GGAAGTTAGGAAGAAGGGTGTGCTGGGCTAACCAGCCCACAGAGCTCAC ATTCCTGTCCCTTGGGTGAAAAATACATGTCCATCCTGATATCTCCTGAAT TCAGAAATTAGCCTCCACATGTGCAATGGCTTTAAGAGCCAGAAGCAGGG TTCTGGGAATTTTGCAAGTTACCTGTGGCCAGGTGTGGTCTCGGTTACCA AATACGGTTACCTGCAGCTTTTTAGTCCTTTGTGCTCCCACGGGTCTACA GAGTCCCATCTGCCCAAAGGTCTTGAAGCTTGACAGGATGTTTTCGATTA CTCAGTCTCCCAGGGCACTACTGGTCCGTAGGATTCGATTGGTCGGGGT AGGAGAGTTAAACAACATTTAAACAGAGTTCTCTCAAAAATGTCTAAAGGG ATTGTAGGTAGATAACATCCAATCACTGTTTGCACTTATCTGAAATCTTCC CTCTTGGCTGCCCCCAGGTATTTACTGTGGAGAACATTGCATAGGAATGT CTGGAAAAAGCTTCTACAACTTGTTACAGCCTTCACATTTGTAGAAGCTTT 52 opt_COX10*- ATGGCCGCCAGCCCCCACACCCTGAGCAGCCGCCTGCTGACCGGCTGC opt_ND6- GTGGGCGGCAGCGTGTGGTACCTGGAGCGCCGCACCATGATGTACGCC 3'UTR* CTGTTCCTGCTGAGCGTGGGCCTGGTGATGGGCTTCGTGGGCTTCAGCA GCAAGCCCAGCCCCATCTACGGCGGCCTGGTGCTGATCGTGAGCGGCG TGGTGGGCTGCGTGATCATCCTGAACTTCGGCGGCGGCTACATGGGCCT GATGGTGTTCCTGATCTACCTGGGCGGCATGATGGTGGTGTTCGGCTAC ACCACCGCCATGGCCATCGAGGAGTACCCCGAGGCCTGGGGCAGCGGC GTGGAGGTGCTGGTGAGCGTGCTGGTGGGCCTGGCCATGGAGGTGGGC CTGGTGCTGTGGGTGAAGGAGTACGACGGCGTGGTGGTGGTGGTGAAC TTCAACAGCGTGGGCAGCTGGATGATCTACGAGGGCGAGGGCAGCGGC CTGATCCGCGAGGACCCCATCGGCGCCGGCGCCCTGTACGACTACGGC CGCTGGCTGGTGGTGGTGACCGGCTGGACCCTGTTCGTGGGCGTGTAC ATCGTGATCGAGATCGCCCGCGGCAACTAAGAGCACTGGGACGCCCACC GCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAATTCTGGAACA CAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAACGAATTCGGTG CTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTACCCAAAATGCT CCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACAAAAAAGGAATT ATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACCCCACCCTCT ATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACACAGCTTCCTCTTT TGGTTCCATCCTTACCACCACACCACACGCACACTCCACATGCCCAGCAG AGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCTGCTGTCTGTA GTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACCCCCTTCCTTGT GACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCCACACATTCTCA ACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCGGCTGCTGTGCAC TGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCAAGCTGGACTG CCA 53 opt_COX10*- ATGGCCGCCAGCCCCCACACCCTGAGCAGCCGCCTGCTGACCGGCTGC ND1- GTGGGCGGCAGCGTGTGGTACCTGGAGCGCCGCACCATGCCCATGGCC 3'UTR AACCTCCTACTCCTCATTGTACCCATTCTAATCGCAATGGCATTCCTAATG CTTACCGAACGAAAAATTCTAGGCTATATGCAACTACGCAAAGGCCCCAA CGTTGTAGGCCCCTACGGGCTACTACAACCCTTCGCTGACGCCATGAAA CTCTTCACCAAAGAGCCCCTAAAACCCGCCACATCTACCATCACCCTCTA CATCACCGCCCCGACCTTAGCTCTCACCATCGCTCTTCTACTATGGACCC CCCTCCCCATGCCCAACCCCCTGGTCAACCTCAACCTAGGCCTCCTATTT ATTCTAGCCACCTCTAGCCTAGCCGTTTACTCAATCCTCTGGTCAGGGTG GGCATCAAACTCAAACTACGCCCTGATCGGCGCACTGCGAGCAGTAGCC CAAACAATCTCATATGAAGTCACCCTAGCCATCATTCTACTATCAACATTA CTAATGAGTGGCTCCTTTAACCTCTCCACCCTTATCACAACACAAGAACAC CTCTGGTTACTCCTGCCATCATGGCCCTTGGCCATGATGTGGTTTATCTC CACACTAGCAGAGACCAACCGAACCCCCTTCGACCTTGCCGAAGGGGAG TCCGAACTAGTCTCAGGCTTCAACATCGAATACGCCGCAGGCCCCTTCGC CCTATTCTTCATGGCCGAATACACAAACATTATTATGATGAACACCCTCAC CACTACAATCTTCCTAGGAACAACATATGACGCACTCTCCCCTGAACTCTA CACAACATATTTTGTCACCAAGACCCTACTTCTAACCTCCCTGTTCTTATG GATTCGAACAGCATACCCCCGATTCCGCTACGACCAACTCATGCACCTCC TATGGAAAAACTTCCTACCACTCACCCTAGCATTACTTATGTGGTATGTCT CCATGCCCATTACAATCTCCAGCATTCCCCCTCAAACCTAAGAGCACTGG GACGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTA ATTCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAAC GAATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTAC CCAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACAA AAAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACC CCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACACAG CTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGCACACTCCACAT GCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCT GCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACC CCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCC ACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCGG CTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCA AGCTGGACTGCCAGCCCCTGTCCTCCCTTCACCCCCATTGCGTATGAGC ATTTCAGAACTCCAAGGAGTCACAGGCATCTTTATAGTTCACGTTAACATA TAGACACTGTTGGAAGCAGTTCCTTCTAAAAGGGTAGCCCTGGACTTAAT ACCAGCCGGATACCTCTGGCCCCCACCCCATTACTGTACCTCTGGAGTCA CTACTGTGGGTCGCCACTCCTCTGCTACACAGCACGGCTTTTTCAAGGCT GTATTGAGAAGGGAAGTTAGGAAGAAGGGTGTGCTGGGCTAACCAGCCC ACAGAGCTCACATTCCTGTCCCTTGGGTGAAAAATACATGTCCATCCTGA TATCTCCTGAATTCAGAAATTAGCCTCCACATGTGCAATGGCTTTAAGAGC CAGAAGCAGGGTTCTGGGAATTTTGCAAGTTACCTGTGGCCAGGTGTGG TCTCGGTTACCAAATACGGTTACCTGCAGCTTTTTAGTCCTTTGTGCTCCC ACGGGTCTACAGAGTCCCATCTGCCCAAAGGTCTTGAAGCTTGACAGGAT GTTTTCGATTACTCAGTCTCCCAGGGCACTACTGGTCCGTAGGATTCGAT TGGTCGGGGTAGGAGAGTTAAACAACATTTAAACAGAGTTCTCTCAAAAA TGTCTAAAGGGATTGTAGGTAGATAACATCCAATCACTGTTTGCACTTATC TGAAATCTTCCCTCTTGGCTGCCCCCAGGTATTTACTGTGGAGAACATTG CATAGGAATGTCTGGAAAAAGCTTCTACAACTTGTTACAGCCTTCACATTT GTAGAAGCTTT 54 opt_COX10*- ATGGCCGCCAGCCCCCACACCCTGAGCAGCCGCCTGCTGACCGGCTGC ND1- GTGGGCGGCAGCGTGTGGTACCTGGAGCGCCGCACCATGCCCATGGCC 3'UTR* AACCTCCTACTCCTCATTGTACCCATTCTAATCGCAATGGCATTCCTAATG CTTACCGAACGAAAAATTCTAGGCTATATGCAACTACGCAAAGGCCCCAA CGTTGTAGGCCCCTACGGGCTACTACAACCCTTCGCTGACGCCATGAAA CTCTTCACCAAAGAGCCCCTAAAACCCGCCACATCTACCATCACCCTCTA CATCACCGCCCCGACCTTAGCTCTCACCATCGCTCTTCTACTATGGACCC CCCTCCCCATGCCCAACCCCCTGGTCAACCTCAACCTAGGCCTCCTATTT ATTCTAGCCACCTCTAGCCTAGCCGTTTACTCAATCCTCTGGTCAGGGTG GGCATCAAACTCAAACTACGCCCTGATCGGCGCACTGCGAGCAGTAGCC CAAACAATCTCATATGAAGTCACCCTAGCCATCATTCTACTATCAACATTA CTAATGAGTGGCTCCTTTAACCTCTCCACCCTTATCACAACACAAGAACAC CTCTGGTTACTCCTGCCATCATGGCCCTTGGCCATGATGTGGTTTATCTC CACACTAGCAGAGACCAACCGAACCCCCTTCGACCTTGCCGAAGGGGAG TCCGAACTAGTCTCAGGCTTCAACATCGAATACGCCGCAGGCCCCTTCGC CCTATTCTTCATGGCCGAATACACAAACATTATTATGATGAACACCCTCAC CACTACAATCTTCCTAGGAACAACATATGACGCACTCTCCCCTGAACTCTA CACAACATATTTTGTCACCAAGACCCTACTTCTAACCTCCCTGTTCTTATG GATTCGAACAGCATACCCCCGATTCCGCTACGACCAACTCATGCACCTCC TATGGAAAAACTTCCTACCACTCACCCTAGCATTACTTATGTGGTATGTCT CCATGCCCATTACAATCTCCAGCATTCCCCCTCAAACCTAAGAGCACTGG GACGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTA ATTCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAAC GAATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTAC CCAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACAA AAAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACC CCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACACAG CTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGCACACTCCACAT GCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCT GCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACC CCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCC ACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCGG CTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCA AGCTGGACTGCCA 55 opt_COX10*- ATGGCCGCCAGCCCCCACACCCTGAGCAGCCGCCTGCTGACCGGCTGC opt_ND1- GTGGGCGGCAGCGTGTGGTACCTGGAGCGCCGCACCATGCCCATGGCC 3'UTR AACCTGCTGCTGCTGATCGTGCCCATCCTGATCGCCATGGCCTTCCTGAT GCTGACCGAGCGCAAGATCCTGGGCTACATGCAGCTGCGCAAGGGCCC CAACGTGGTGGGCCCCTACGGCCTGCTGCAGCCCTTCGCCGACGCCAT GAAGCTGTTCACCAAGGAGCCCCTGAAGCCCGCCACCAGCACCATCACC CTGTACATCACCGCCCCCACCCTGGCCCTGACCATCGCCCTGCTGCTGT GGACCCCCCTGCCCATGCCCAACCCCCTGGTGAACCTGAACCTGGGCCT GCTGTTCATCCTGGCCACCAGCAGCCTGGCCGTGTACAGCATCCTGTGG AGCGGCTGGGCCAGCAACAGCAACTACGCCCTGATCGGCGCCCTGCGC GCCGTGGCCCAGACCATCAGCTACGAGGTGACCCTGGCCATCATCCTGC TGAGCACCCTGCTGATGAGCGGCAGCTTCAACCTGAGCACCCTGATCAC CACCCAGGAGCACCTGTGGCTGCTGCTGCCCAGCTGGCCCCTGGCCAT GATGTGGTTCATCAGCACCCTGGCCGAGACCAACCGCACCCCCTTCGAC CTGGCCGAGGGCGAGAGCGAGCTGGTGAGCGGCTTCAACATCGAGTAC GCCGCCGGCCCCTTCGCCCTGTTCTTCATGGCCGAGTACACCAACATCA TCATGATGAACACCCTGACCACCACCATCTTCCTGGGCACCACCTACGAC GCCCTGAGCCCCGAGCTGTACACCACCTACTTCGTGACCAAGACCCTGC TGCTGACCAGCCTGTTCCTGTGGATCCGCACCGCCTACCCCCGCTTCCG
CTACGACCAGCTGATGCACCTGCTGTGGAAGAACTTCCTGCCCCTGACC CTGGCCCTGCTGATGTGGTACGTGAGCATGCCCATCACCATCAGCAGCA TCCCCCCCCAGACCTAAGAGCACTGGGACGCCCACCGCCCCTTTCCCTC CGCTGCCAGGCGAGCATGTTGTGGTAATTCTGGAACACAAGAAGAGAAAT TGCTGGGTTTAGAACAAGATTATAAACGAATTCGGTGCTCAGTGATCACTT GACAGTTTTTTTTTTTTTTAAATATTACCCAAAATGCTCCCCAAATAAGAAA TGCATCAGCTCAGTCAGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAG GGTCTTTTATACATCTCTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCT CCTCACATGGGGGTACACATACACAGCTTCCTCTTTTGGTTCCATCCTTAC CACCACACCACACGCACACTCCACATGCCCAGCAGAGTGGCACTTGGTG GCCAGAAAGTGTGAGCCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCA GGTCCCTCAAAGGCCTCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGG CCTGCATTTTTGGTTTTCCCCACCCCACACATTCTCAACCATAGTCCTTCT AACAATACCAATAGCTAGGACCCGGCTGCTGTGCACTGGGACTGGGGAT TCCACATGTTTGCCTTGGGAGTCTCAAGCTGGACTGCCAGCCCCTGTCCT CCCTTCACCCCCATTGCGTATGAGCATTTCAGAACTCCAAGGAGTCACAG GCATCTTTATAGTTCACGTTAACATATAGACACTGTTGGAAGCAGTTCCTT CTAAAAGGGTAGCCCTGGACTTAATACCAGCCGGATACCTCTGGCCCCC ACCCCATTACTGTACCTCTGGAGTCACTACTGTGGGTCGCCACTCCTCTG CTACACAGCACGGCTTTTTCAAGGCTGTATTGAGAAGGGAAGTTAGGAAG AAGGGTGTGCTGGGCTAACCAGCCCACAGAGCTCACATTCCTGTCCCTT GGGTGAAAAATACATGTCCATCCTGATATCTCCTGAATTCAGAAATTAGCC TCCACATGTGCAATGGCTTTAAGAGCCAGAAGCAGGGTTCTGGGAATTTT GCAAGTTACCTGTGGCCAGGTGTGGTCTCGGTTACCAAATACGGTTACCT GCAGCTTTTTAGTCCTTTGTGCTCCCACGGGTCTACAGAGTCCCATCTGC CCAAAGGTCTTGAAGCTTGACAGGATGTTTTCGATTACTCAGTCTCCCAG GGCACTACTGGTCCGTAGGATTCGATTGGTCGGGGTAGGAGAGTTAAAC AACATTTAAACAGAGTTCTCTCAAAAATGTCTAAAGGGATTGTAGGTAGAT AACATCCAATCACTGTTTGCACTTATCTGAAATCTTCCCTCTTGGCTGCCC CCAGGTATTTACTGTGGAGAACATTGCATAGGAATGTCTGGAAAAAGCTT CTACAACTTGTTACAGCCTTCACATTTGTAGAAGCTTT 56 opt_COX10*- ATGGCCGCCAGCCCCCACACCCTGAGCAGCCGCCTGCTGACCGGCTGC opt_ND1- GTGGGCGGCAGCGTGTGGTACCTGGAGCGCCGCACCATGCCCATGGCC 3'UTR* AACCTGCTGCTGCTGATCGTGCCCATCCTGATCGCCATGGCCTTCCTGAT GCTGACCGAGCGCAAGATCCTGGGCTACATGCAGCTGCGCAAGGGCCC CAACGTGGTGGGCCCCTACGGCCTGCTGCAGCCCTTCGCCGACGCCAT GAAGCTGTTCACCAAGGAGCCCCTGAAGCCCGCCACCAGCACCATCACC CTGTACATCACCGCCCCCACCCTGGCCCTGACCATCGCCCTGCTGCTGT GGACCCCCCTGCCCATGCCCAACCCCCTGGTGAACCTGAACCTGGGCCT GCTGTTCATCCTGGCCACCAGCAGCCTGGCCGTGTACAGCATCCTGTGG AGCGGCTGGGCCAGCAACAGCAACTACGCCCTGATCGGCGCCCTGCGC GCCGTGGCCCAGACCATCAGCTACGAGGTGACCCTGGCCATCATCCTGC TGAGCACCCTGCTGATGAGCGGCAGCTTCAACCTGAGCACCCTGATCAC CACCCAGGAGCACCTGTGGCTGCTGCTGCCCAGCTGGCCCCTGGCCAT GATGTGGTTCATCAGCACCCTGGCCGAGACCAACCGCACCCCCTTCGAC CTGGCCGAGGGCGAGAGCGAGCTGGTGAGCGGCTTCAACATCGAGTAC GCCGCCGGCCCCTTCGCCCTGTTCTTCATGGCCGAGTACACCAACATCA TCATGATGAACACCCTGACCACCACCATCTTCCTGGGCACCACCTACGAC GCCCTGAGCCCCGAGCTGTACACCACCTACTTCGTGACCAAGACCCTGC TGCTGACCAGCCTGTTCCTGTGGATCCGCACCGCCTACCCCCGCTTCCG CTACGACCAGCTGATGCACCTGCTGTGGAAGAACTTCCTGCCCCTGACC CTGGCCCTGCTGATGTGGTACGTGAGCATGCCCATCACCATCAGCAGCA TCCCCCCCCAGACCTAAGAGCACTGGGACGCCCACCGCCCCTTTCCCTC CGCTGCCAGGCGAGCATGTTGTGGTAATTCTGGAACACAAGAAGAGAAAT TGCTGGGTTTAGAACAAGATTATAAACGAATTCGGTGCTCAGTGATCACTT GACAGTTTTTTTTTTTTTTAAATATTACCCAAAATGCTCCCCAAATAAGAAA TGCATCAGCTCAGTCAGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAG GGTCTTTTATACATCTCTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCT CCTCACATGGGGGTACACATACACAGCTTCCTCTTTTGGTTCCATCCTTAC CACCACACCACACGCACACTCCACATGCCCAGCAGAGTGGCACTTGGTG GCCAGAAAGTGTGAGCCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCA GGTCCCTCAAAGGCCTCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGG CCTGCATTTTTGGTTTTCCCCACCCCACACATTCTCAACCATAGTCCTTCT AACAATACCAATAGCTAGGACCCGGCTGCTGTGCACTGGGACTGGGGAT TCCACATGTTTGCCTTGGGAGTCTCAAGCTGGACTGCCA 57 COX8- ATGTCCGTCCTGACGCGCCTGCTGCTGCGGGGCTTGACACGGCTCGGCT ND4- CGGCGGCTCCAGTGCGGCGCGCCAGAATCCATTCGTTGATGCTAAAACT 3'UTR AATCGTCCCAACAATTATGTTACTACCACTGACATGGCTTTCCAAAAAACA CATGATTTGGATCAACACAACCACCCACAGCCTAATTATTAGCATCATCCC TCTACTATTTTTTAACCAAATCAACAACAACCTATTTAGCTGTTCCCCAACC TTTTCCTCCGACCCCCTAACAACCCCCCTCCTAATGCTAACTACCTGGCT CCTACCCCTCACAATCATGGCAAGCCAACGCCACTTATCCAGTGAACCAC TATCACGAAAAAAACTCTACCTCTCTATGCTAATCTCCCTACAAATCTCCTT AATTATGACATTCACAGCCACAGAACTAATCATGTTTTATATCTTCTTCGAA ACCACACTTATCCCCACCTTGGCTATCATCACCCGATGGGGCAACCAGCC AGAACGCCTGAACGCAGGCACATACTTCCTATTCTACACCCTAGTAGGCT CCCTTCCCCTACTCATCGCACTAATTTACACTCACAACACCCTAGGCTCAC TAAACATTCTACTACTCACTCTCACTGCCCAAGAACTATCAAACTCCTGGG CCAACAACTTAATGTGGCTAGCTTACACAATGGCTTTTATGGTAAAGATGC CTCTTTACGGACTCCACTTATGGCTCCCTAAAGCCCATGTCGAAGCCCCC ATCGCTGGGTCAATGGTACTTGCCGCAGTACTCTTAAAACTAGGCGGCTA TGGTATGATGCGCCTCACACTCATTCTCAACCCCCTGACAAAACACATGG CCTACCCCTTCCTTGTACTATCCCTATGGGGCATGATTATGACAAGCTCC ATCTGCCTACGACAAACAGACCTAAAATCGCTCATTGCATACTCTTCAATC AGCCACATGGCCCTCGTAGTAACAGCCATTCTCATCCAAACCCCCTGGAG CTTCACCGGCGCAGTCATTCTCATGATCGCCCACGGGCTTACATCCTCAT TACTATTCTGCCTAGCAAACTCAAACTACGAACGCACTCACAGTCGCATC ATGATCCTCTCTCAAGGACTTCAAACTCTACTCCCACTAATGGCTTTTTGG TGGCTTCTAGCAAGCCTCGCTAACCTCGCCTTACCCCCCACTATTAACCT ACTGGGAGAACTCTCTGTGCTAGTAACCACGTTCTCCTGGTCAAATATCA CTCTCCTACTTACAGGACTCAACATGCTAGTCACAGCCCTATACTCCCTCT ACATGTTTACCACAACACAATGGGGCTCACTCACCCACCACATTAACAAC ATGAAACCCTCATTCACACGAGAAAACACCCTCATGTTCATGCACCTATCC CCCATTCTCCTCCTATCCCTCAACCCCGACATCATTACCGGGTTTTCCTCT TAAGAGCACTGGGACGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAG CATGTTGTGGTAATTCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAA CAAGATTATAAACGAATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTT TTTTAAATATTACCCAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGT CAGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATC TCTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTA CACATACACAGCTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGC ACACTCCACATGCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAG CCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCC TCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTT TCCCCACCCCACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCT AGGACCCGGCTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTT GGGAGTCTCAAGCTGGACTGCCAGCCCCTGTCCTCCCTTCACCCCCATT GCGTATGAGCATTTCAGAACTCCAAGGAGTCACAGGCATCTTTATAGTTC ACGTTAACATATAGACACTGTTGGAAGCAGTTCCTTCTAAAAGGGTAGCC CTGGACTTAATACCAGCCGGATACCTCTGGCCCCCACCCCATTACTGTAC CTCTGGAGTCACTACTGTGGGTCGCCACTCCTCTGCTACACAGCACGGC TTTTTCAAGGCTGTATTGAGAAGGGAAGTTAGGAAGAAGGGTGTGCTGGG CTAACCAGCCCACAGAGCTCACATTCCTGTCCCTTGGGTGAAAAATACAT GTCCATCCTGATATCTCCTGAATTCAGAAATTAGCCTCCACATGTGCAATG GCTTTAAGAGCCAGAAGCAGGGTTCTGGGAATTTTGCAAGTTACCTGTGG CCAGGTGTGGTCTCGGTTACCAAATACGGTTACCTGCAGCTTTTTAGTCC TTTGTGCTCCCACGGGTCTACAGAGTCCCATCTGCCCAAAGGTCTTGAAG CTTGACAGGATGTTTTCGATTACTCAGTCTCCCAGGGCACTACTGGTCCG TAGGATTCGATTGGTCGGGGTAGGAGAGTTAAACAACATTTAAACAGAGT TCTCTCAAAAATGTCTAAAGGGATTGTAGGTAGATAACATCCAATCACTGT TTGCACTTATCTGAAATCTTCCCTCTTGGCTGCCCCCAGGTATTTACTGTG GAGAACATTGCATAGGAATGTCTGGAAAAAGCTTCTACAACTTGTTACAG CCTTCACATTTGTAGAAGCTTT 58 COX8- ATGTCCGTCCTGACGCGCCTGCTGCTGCGGGGCTTGACACGGCTCGGCT ND4- CGGCGGCTCCAGTGCGGCGCGCCAGAATCCATTCGTTGATGCTAAAACT 3'UTR* AATCGTCCCAACAATTATGTTACTACCACTGACATGGCTTTCCAAAAAACA CATGATTTGGATCAACACAACCACCCACAGCCTAATTATTAGCATCATCCC TCTACTATTTTTTAACCAAATCAACAACAACCTATTTAGCTGTTCCCCAACC TTTTCCTCCGACCCCCTAACAACCCCCCTCCTAATGCTAACTACCTGGCT CCTACCCCTCACAATCATGGCAAGCCAACGCCACTTATCCAGTGAACCAC TATCACGAAAAAAACTCTACCTCTCTATGCTAATCTCCCTACAAATCTCCTT AATTATGACATTCACAGCCACAGAACTAATCATGTTTTATATCTTCTTCGAA ACCACACTTATCCCCACCTTGGCTATCATCACCCGATGGGGCAACCAGCC AGAACGCCTGAACGCAGGCACATACTTCCTATTCTACACCCTAGTAGGCT CCCTTCCCCTACTCATCGCACTAATTTACACTCACAACACCCTAGGCTCAC TAAACATTCTACTACTCACTCTCACTGCCCAAGAACTATCAAACTCCTGGG CCAACAACTTAATGTGGCTAGCTTACACAATGGCTTTTATGGTAAAGATGC CTCTTTACGGACTCCACTTATGGCTCCCTAAAGCCCATGTCGAAGCCCCC ATCGCTGGGTCAATGGTACTTGCCGCAGTACTCTTAAAACTAGGCGGCTA TGGTATGATGCGCCTCACACTCATTCTCAACCCCCTGACAAAACACATGG CCTACCCCTTCCTTGTACTATCCCTATGGGGCATGATTATGACAAGCTCC ATCTGCCTACGACAAACAGACCTAAAATCGCTCATTGCATACTCTTCAATC AGCCACATGGCCCTCGTAGTAACAGCCATTCTCATCCAAACCCCCTGGAG CTTCACCGGCGCAGTCATTCTCATGATCGCCCACGGGCTTACATCCTCAT TACTATTCTGCCTAGCAAACTCAAACTACGAACGCACTCACAGTCGCATC ATGATCCTCTCTCAAGGACTTCAAACTCTACTCCCACTAATGGCTTTTTGG TGGCTTCTAGCAAGCCTCGCTAACCTCGCCTTACCCCCCACTATTAACCT ACTGGGAGAACTCTCTGTGCTAGTAACCACGTTCTCCTGGTCAAATATCA CTCTCCTACTTACAGGACTCAACATGCTAGTCACAGCCCTATACTCCCTCT ACATGTTTACCACAACACAATGGGGCTCACTCACCCACCACATTAACAAC ATGAAACCCTCATTCACACGAGAAAACACCCTCATGTTCATGCACCTATCC CCCATTCTCCTCCTATCCCTCAACCCCGACATCATTACCGGGTTTTCCTCT TAAGAGCACTGGGACGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAG CATGTTGTGGTAATTCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAA CAAGATTATAAACGAATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTT TTTTAAATATTACCCAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGT CAGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATC TCTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTA CACATACACAGCTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGC ACACTCCACATGCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAG CCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCC TCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTT TCCCCACCCCACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCT AGGACCCGGCTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTT GGGAGTCTCAAGCTGGACTGCCA 59 COX8- ATGTCCGTCCTGACGCGCCTGCTGCTGCGGGGCTTGACACGGCTCGGCT opt_ND4- CGGCGGCTCCAGTGCGGCGCGCCAGAATCCATTCGTTGATGCTGAAGCT 3'UTR GATCGTGCCCACCATCATGCTGCTGCCTCTGACCTGGCTGAGCAAGAAA CACATGATCTGGATCAACACCACCACGCACAGCCTGATCATCAGCATCAT CCCTCTGCTGTTCTTCAACCAGATCAACAACAACCTGTTCAGCTGCAGCC CCACCTTCAGCAGCGACCCTCTGACAACACCTCTGCTGATGCTGACCACC TGGCTGCTGCCCCTCACAATCATGGCCTCTCAGAGACACCTGAGCAGCG AGCCCCTGAGCCGGAAGAAACTGTACCTGAGCATGCTGATCTCCCTGCA GATCTCTCTGATCATGACCTTCACCGCCACCGAGCTGATCATGTTCTACA TCTTTTTCGAGACAACGCTGATCCCCACACTGGCCATCATCACCAGATGG GGCAACCAGCCTGAGAGACTGAACGCCGGCACCTACTTTCTGTTCTACAC CCTCGTGGGCAGCCTGCCACTGCTGATTGCCCTGATCTACACCCACAAC ACCCTGGGCTCCCTGAACATCCTGCTGCTGACACTGACAGCCCAAGAGC TGAGCAACAGCTGGGCCAACAATCTGATGTGGCTGGCCTACACAATGGC CTTCATGGTCAAGATGCCCCTGTACGGCCTGCACCTGTGGCTGCCTAAA GCTCATGTGGAAGCCCCTATCGCCGGCTCTATGGTGCTGGCTGCAGTGC TGCTGAAACTCGGCGGCTACGGCATGATGCGGCTGACCCTGATTCTGAA TCCCCTGACCAAGCACATGGCCTATCCATTTCTGGTGCTGAGCCTGTGGG GCATGATTATGACCAGCAGCATCTGCCTGCGGCAGACCGATCTGAAGTC CCTGATCGCCTACAGCTCCATCAGCCACATGGCCCTGGTGGTCACCGCC ATCCTGATTCAGACCCCTTGGAGCTTTACAGGCGCCGTGATCCTGATGAT TGCCCACGGCCTGACAAGCAGCCTGCTGTTTTGTCTGGCCAACAGCAAC TACGAGCGGACCCACAGCAGAATCATGATCCTGTCTCAGGGCCTGCAGA CCCTCCTGCCTCTTATGGCTTTTTGGTGGCTGCTGGCCTCTCTGGCCAAT CTGGCACTGCCTCCTACCATCAATCTGCTGGGCGAGCTGAGCGTGCTGG TCACCACATTCAGCTGGTCCAATATCACCCTGCTGCTCACCGGCCTGAAC ATGCTGGTTACAGCCCTGTACTCCCTGTACATGTTCACCACCACACAGTG GGGAAGCCTGACACACCACATCAACAATATGAAGCCCAGCTTCACCCGC GAGAACACCCTGATGTTCATGCATCTGAGCCCCATTCTGCTGCTGTCCCT GAATCCTGATATCATCACCGGCTTCTCCAGCTGAGAGCACTGGGACGCC CACCGCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAATTCTG GAACACAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAACGAATT CGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTACCCAAA ATGCTCCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACAAAAAAG GAATTATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACCCCAC CCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACACAGCTTCC TCTTTTGGTTCCATCCTTACCACCACACCACACGCACACTCCACATGCCC AGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCTGCTG TCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACCCCCTT CCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCCACACA TTCTCAACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCGGCTGCT GTGCACTGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCAAGCT GGACTGCCAGCCCCTGTCCTCCCTTCACCCCCATTGCGTATGAGCATTTC AGAACTCCAAGGAGTCACAGGCATCTTTATAGTTCACGTTAACATATAGAC ACTGTTGGAAGCAGTTCCTTCTAAAAGGGTAGCCCTGGACTTAATACCAG CCGGATACCTCTGGCCCCCACCCCATTACTGTACCTCTGGAGTCACTACT GTGGGTCGCCACTCCTCTGCTACACAGCACGGCTTTTTCAAGGCTGTATT GAGAAGGGAAGTTAGGAAGAAGGGTGTGCTGGGCTAACCAGCCCACAGA GCTCACATTCCTGTCCCTTGGGTGAAAAATACATGTCCATCCTGATATCTC CTGAATTCAGAAATTAGCCTCCACATGTGCAATGGCTTTAAGAGCCAGAA GCAGGGTTCTGGGAATTTTGCAAGTTACCTGTGGCCAGGTGTGGTCTCG GTTACCAAATACGGTTACCTGCAGCTTTTTAGTCCTTTGTGCTCCCACGG GTCTACAGAGTCCCATCTGCCCAAAGGTCTTGAAGCTTGACAGGATGTTT TCGATTACTCAGTCTCCCAGGGCACTACTGGTCCGTAGGATTCGATTGGT CGGGGTAGGAGAGTTAAACAACATTTAAACAGAGTTCTCTCAAAAATGTCT AAAGGGATTGTAGGTAGATAACATCCAATCACTGTTTGCACTTATCTGAAA TCTTCCCTCTTGGCTGCCCCCAGGTATTTACTGTGGAGAACATTGCATAG GAATGTCTGGAAAAAGCTTCTACAACTTGTTACAGCCTTCACATTTGTAGA AGCTTT 60 COX8- ATGTCCGTCCTGACGCGCCTGCTGCTGCGGGGCTTGACACGGCTCGGCT opt_ND4- CGGCGGCTCCAGTGCGGCGCGCCAGAATCCATTCGTTGATGCTGAAGCT 3'UTR* GATCGTGCCCACCATCATGCTGCTGCCTCTGACCTGGCTGAGCAAGAAA CACATGATCTGGATCAACACCACCACGCACAGCCTGATCATCAGCATCAT CCCTCTGCTGTTCTTCAACCAGATCAACAACAACCTGTTCAGCTGCAGCC CCACCTTCAGCAGCGACCCTCTGACAACACCTCTGCTGATGCTGACCACC TGGCTGCTGCCCCTCACAATCATGGCCTCTCAGAGACACCTGAGCAGCG AGCCCCTGAGCCGGAAGAAACTGTACCTGAGCATGCTGATCTCCCTGCA GATCTCTCTGATCATGACCTTCACCGCCACCGAGCTGATCATGTTCTACA TCTTTTTCGAGACAACGCTGATCCCCACACTGGCCATCATCACCAGATGG GGCAACCAGCCTGAGAGACTGAACGCCGGCACCTACTTTCTGTTCTACAC CCTCGTGGGCAGCCTGCCACTGCTGATTGCCCTGATCTACACCCACAAC ACCCTGGGCTCCCTGAACATCCTGCTGCTGACACTGACAGCCCAAGAGC TGAGCAACAGCTGGGCCAACAATCTGATGTGGCTGGCCTACACAATGGC CTTCATGGTCAAGATGCCCCTGTACGGCCTGCACCTGTGGCTGCCTAAA GCTCATGTGGAAGCCCCTATCGCCGGCTCTATGGTGCTGGCTGCAGTGC TGCTGAAACTCGGCGGCTACGGCATGATGCGGCTGACCCTGATTCTGAA TCCCCTGACCAAGCACATGGCCTATCCATTTCTGGTGCTGAGCCTGTGGG GCATGATTATGACCAGCAGCATCTGCCTGCGGCAGACCGATCTGAAGTC CCTGATCGCCTACAGCTCCATCAGCCACATGGCCCTGGTGGTCACCGCC ATCCTGATTCAGACCCCTTGGAGCTTTACAGGCGCCGTGATCCTGATGAT TGCCCACGGCCTGACAAGCAGCCTGCTGTTTTGTCTGGCCAACAGCAAC
TACGAGCGGACCCACAGCAGAATCATGATCCTGTCTCAGGGCCTGCAGA CCCTCCTGCCTCTTATGGCTTTTTGGTGGCTGCTGGCCTCTCTGGCCAAT CTGGCACTGCCTCCTACCATCAATCTGCTGGGCGAGCTGAGCGTGCTGG TCACCACATTCAGCTGGTCCAATATCACCCTGCTGCTCACCGGCCTGAAC ATGCTGGTTACAGCCCTGTACTCCCTGTACATGTTCACCACCACACAGTG GGGAAGCCTGACACACCACATCAACAATATGAAGCCCAGCTTCACCCGC GAGAACACCCTGATGTTCATGCATCTGAGCCCCATTCTGCTGCTGTCCCT GAATCCTGATATCATCACCGGCTTCTCCAGCTGAGAGCACTGGGACGCC CACCGCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAATTCTG GAACACAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAACGAATT CGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTACCCAAA ATGCTCCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACAAAAAAG GAATTATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACCCCAC CCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACACAGCTTCC TCTTTTGGTTCCATCCTTACCACCACACCACACGCACACTCCACATGCCC AGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCTGCTG TCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACCCCCTT CCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCCACACA TTCTCAACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCGGCTGCT GTGCACTGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCAAGCT GGACTGCCA 61 COX8- ATGTCCGTCCTGACGCGCCTGCTGCTGCGGGGCTTGACACGGCTCGGCT opt_ND4*- CGGCGGCTCCAGTGCGGCGCGCCAGAATCCATTCGTTGATGCTGAAGCT 3'UTR GATCGTGCCCACCATCATGCTGCTGCCCCTGACCTGGCTGAGCAAGAAG CACATGATCTGGATCAACACCACCACCCACAGCCTGATCATCAGCATCAT CCCCCTGCTGTTCTTCAACCAGATCAACAACAACCTGTTCAGCTGCAGCC CCACCTTCAGCAGCGACCCCCTGACCACCCCCCTGCTGATGCTGACCAC CTGGCTGCTGCCCCTGACCATCATGGCCAGCCAGCGCCACCTGAGCAGC GAGCCCCTGAGCCGCAAGAAGCTGTACCTGAGCATGCTGATCAGCCTGC AGATCAGCCTGATCATGACCTTCACCGCCACCGAGCTGATCATGTTCTAC ATCTTCTTCGAGACCACCCTGATCCCCACCCTGGCCATCATCACCCGCTG GGGCAACCAGCCCGAGCGCCTGAACGCCGGCACCTACTTCCTGTTCTAC ACCCTGGTGGGCAGCCTGCCCCTGCTGATCGCCCTGATCTACACCCACA ACACCCTGGGCAGCCTGAACATCCTGCTGCTGACCCTGACCGCCCAGGA GCTGAGCAACAGCTGGGCCAACAACCTGATGTGGCTGGCCTACACCATG GCCTTCATGGTGAAGATGCCCCTGTACGGCCTGCACCTGTGGCTGCCCA AGGCCCACGTGGAGGCCCCCATCGCCGGCAGCATGGTGCTGGCCGCCG TGCTGCTGAAGCTGGGCGGCTACGGCATGATGCGCCTGACCCTGATCCT GAACCCCCTGACCAAGCACATGGCCTACCCCTTCCTGGTGCTGAGCCTG TGGGGCATGATCATGACCAGCAGCATCTGCCTGCGCCAGACCGACCTGA AGAGCCTGATCGCCTACAGCAGCATCAGCCACATGGCCCTGGTGGTGAC CGCCATCCTGATCCAGACCCCCTGGAGCTTCACCGGCGCCGTGATCCTG ATGATCGCCCACGGCCTGACCAGCAGCCTGCTGTTCTGCCTGGCCAACA GCAACTACGAGCGCACCCACAGCCGCATCATGATCCTGAGCCAGGGCCT GCAGACCCTGCTGCCCCTGATGGCCTTCTGGTGGCTGCTGGCCAGCCTG GCCAACCTGGCCCTGCCCCCCACCATCAACCTGCTGGGCGAGCTGAGC GTGCTGGTGACCACCTTCAGCTGGAGCAACATCACCCTGCTGCTGACCG GCCTGAACATGCTGGTGACCGCCCTGTACAGCCTGTACATGTTCACCACC ACCCAGTGGGGCAGCCTGACCCACCACATCAACAACATGAAGCCCAGCT TCACCCGCGAGAACACCCTGATGTTCATGCACCTGAGCCCCATCCTGCT GCTGAGCCTGAACCCCGACATCATCACCGGCTTCAGCAGCTAAGAGCAC TGGGACGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTG GTAATTCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATA AACGAATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATAT TACCCAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATA CAAAAAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCA ACCCCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACAC AGCTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGCACACTCCA CATGCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGA TCTGCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCA CCCCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACC CCACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCG GCTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCT CAAGCTGGACTGCCAGCCCCTGTCCTCCCTTCACCCCCATTGCGTATGA GCATTTCAGAACTCCAAGGAGTCACAGGCATCTTTATAGTTCACGTTAACA TATAGACACTGTTGGAAGCAGTTCCTTCTAAAAGGGTAGCCCTGGACTTA ATACCAGCCGGATACCTCTGGCCCCCACCCCATTACTGTACCTCTGGAGT CACTACTGTGGGTCGCCACTCCTCTGCTACACAGCACGGCTTTTTCAAGG CTGTATTGAGAAGGGAAGTTAGGAAGAAGGGTGTGCTGGGCTAACCAGC CCACAGAGCTCACATTCCTGTCCCTTGGGTGAAAAATACATGTCCATCCT GATATCTCCTGAATTCAGAAATTAGCCTCCACATGTGCAATGGCTTTAAGA GCCAGAAGCAGGGTTCTGGGAATTTTGCAAGTTACCTGTGGCCAGGTGT GGTCTCGGTTACCAAATACGGTTACCTGCAGCTTTTTAGTCCTTTGTGCTC CCACGGGTCTACAGAGTCCCATCTGCCCAAAGGTCTTGAAGCTTGACAG GATGTTTTCGATTACTCAGTCTCCCAGGGCACTACTGGTCCGTAGGATTC GATTGGTCGGGGTAGGAGAGTTAAACAACATTTAAACAGAGTTCTCTCAA AAATGTCTAAAGGGATTGTAGGTAGATAACATCCAATCACTGTTTGCACTT ATCTGAAATCTTCCCTCTTGGCTGCCCCCAGGTATTTACTGTGGAGAACA TTGCATAGGAATGTCTGGAAAAAGCTTCTACAACTTGTTACAGCCTTCACA TTTGTAGAAGCTTT 62 COX8- ATGTCCGTCCTGACGCGCCTGCTGCTGCGGGGCTTGACACGGCTCGGCT opt_ND4*- CGGCGGCTCCAGTGCGGCGCGCCAGAATCCATTCGTTGATGCTGAAGCT 3'UTR* GATCGTGCCCACCATCATGCTGCTGCCCCTGACCTGGCTGAGCAAGAAG CACATGATCTGGATCAACACCACCACCCACAGCCTGATCATCAGCATCAT CCCCCTGCTGTTCTTCAACCAGATCAACAACAACCTGTTCAGCTGCAGCC CCACCTTCAGCAGCGACCCCCTGACCACCCCCCTGCTGATGCTGACCAC CTGGCTGCTGCCCCTGACCATCATGGCCAGCCAGCGCCACCTGAGCAGC GAGCCCCTGAGCCGCAAGAAGCTGTACCTGAGCATGCTGATCAGCCTGC AGATCAGCCTGATCATGACCTTCACCGCCACCGAGCTGATCATGTTCTAC ATCTTCTTCGAGACCACCCTGATCCCCACCCTGGCCATCATCACCCGCTG GGGCAACCAGCCCGAGCGCCTGAACGCCGGCACCTACTTCCTGTTCTAC ACCCTGGTGGGCAGCCTGCCCCTGCTGATCGCCCTGATCTACACCCACA ACACCCTGGGCAGCCTGAACATCCTGCTGCTGACCCTGACCGCCCAGGA GCTGAGCAACAGCTGGGCCAACAACCTGATGTGGCTGGCCTACACCATG GCCTTCATGGTGAAGATGCCCCTGTACGGCCTGCACCTGTGGCTGCCCA AGGCCCACGTGGAGGCCCCCATCGCCGGCAGCATGGTGCTGGCCGCCG TGCTGCTGAAGCTGGGCGGCTACGGCATGATGCGCCTGACCCTGATCCT GAACCCCCTGACCAAGCACATGGCCTACCCCTTCCTGGTGCTGAGCCTG TGGGGCATGATCATGACCAGCAGCATCTGCCTGCGCCAGACCGACCTGA AGAGCCTGATCGCCTACAGCAGCATCAGCCACATGGCCCTGGTGGTGAC CGCCATCCTGATCCAGACCCCCTGGAGCTTCACCGGCGCCGTGATCCTG ATGATCGCCCACGGCCTGACCAGCAGCCTGCTGTTCTGCCTGGCCAACA GCAACTACGAGCGCACCCACAGCCGCATCATGATCCTGAGCCAGGGCCT GCAGACCCTGCTGCCCCTGATGGCCTTCTGGTGGCTGCTGGCCAGCCTG GCCAACCTGGCCCTGCCCCCCACCATCAACCTGCTGGGCGAGCTGAGC GTGCTGGTGACCACCTTCAGCTGGAGCAACATCACCCTGCTGCTGACCG GCCTGAACATGCTGGTGACCGCCCTGTACAGCCTGTACATGTTCACCACC ACCCAGTGGGGCAGCCTGACCCACCACATCAACAACATGAAGCCCAGCT TCACCCGCGAGAACACCCTGATGTTCATGCACCTGAGCCCCATCCTGCT GCTGAGCCTGAACCCCGACATCATCACCGGCTTCAGCAGCTAAGAGCAC TGGGACGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTG GTAATTCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATA AACGAATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATAT TACCCAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATA CAAAAAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCA ACCCCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACAC AGCTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGCACACTCCA CATGCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGA TCTGCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCA CCCCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACC CCACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCG GCTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCT CAAGCTGGACTGCCA 63 COX8- ATGTCCGTCCTGACGCGCCTGCTGCTGCGGGGCTTGACACGGCTCGGCT ND6- CGGCGGCTCCAGTGCGGCGCGCCAGAATCCATTCGTTGATGATGTATGC 3'UTR TTTGTTTCTGTTGAGTGTGGGTTTAGTAATGGGGTTTGTGGGGTTTTCTTC TAAGCCTTCTCCTATTTATGGGGGTTTAGTATTGATTGTTAGCGGTGTGGT CGGGTGTGTTATTATTCTGAATTTTGGGGGAGGTTATATGGGTTTAATGGT TTTTTTAATTTATTTAGGGGGAATGATGGTTGTCTTTGGATATACTACAGC GATGGCTATTGAGGAGTATCCTGAGGCATGGGGGTCAGGGGTTGAGGTC TTGGTGAGTGTTTTAGTGGGGTTAGCGATGGAGGTAGGATTGGTGCTGT GGGTGAAAGAGTATGATGGGGTGGTGGTTGTGGTAAACTTTAATAGTGTA GGAAGCTGGATGATTTATGAAGGAGAGGGGTCAGGGTTGATTCGGGAGG ATCCTATTGGTGCGGGGGCTTTGTATGATTATGGGCGTTGGTTAGTAGTA GTTACTGGTTGGACATTGTTTGTTGGTGTATATATTGTAATTGAGATTGCT CGGGGGAATTAGGAGCACTGGGACGCCCACCGCCCCTTTCCCTCCGCTG CCAGGCGAGCATGTTGTGGTAATTCTGGAACACAAGAAGAGAAATTGCTG GGTTTAGAACAAGATTATAAACGAATTCGGTGCTCAGTGATCACTTGACA GTTTTTTTTTTTTTTAAATATTACCCAAAATGCTCCCCAAATAAGAAATGCA TCAGCTCAGTCAGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGGTC TTTTATACATCTCTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCTCA CATGGGGGTACACATACACAGCTTCCTCTTTTGGTTCCATCCTTACCACC ACACCACACGCACACTCCACATGCCCAGCAGAGTGGCACTTGGTGGCCA GAAAGTGTGAGCCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGGTC CCTCAAAGGCCTCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCCTG CATTTTTGGTTTTCCCCACCCCACACATTCTCAACCATAGTCCTTCTAACA ATACCAATAGCTAGGACCCGGCTGCTGTGCACTGGGACTGGGGATTCCA CATGTTTGCCTTGGGAGTCTCAAGCTGGACTGCCAGCCCCTGTCCTCCCT TCACCCCCATTGCGTATGAGCATTTCAGAACTCCAAGGAGTCACAGGCAT CTTTATAGTTCACGTTAACATATAGACACTGTTGGAAGCAGTTCCTTCTAA AAGGGTAGCCCTGGACTTAATACCAGCCGGATACCTCTGGCCCCCACCC CATTACTGTACCTCTGGAGTCACTACTGTGGGTCGCCACTCCTCTGCTAC ACAGCACGGCTTTTTCAAGGCTGTATTGAGAAGGGAAGTTAGGAAGAAGG GTGTGCTGGGCTAACCAGCCCACAGAGCTCACATTCCTGTCCCTTGGGT GAAAAATACATGTCCATCCTGATATCTCCTGAATTCAGAAATTAGCCTCCA CATGTGCAATGGCTTTAAGAGCCAGAAGCAGGGTTCTGGGAATTTTGCAA GTTACCTGTGGCCAGGTGTGGTCTCGGTTACCAAATACGGTTACCTGCAG CTTTTTAGTCCTTTGTGCTCCCACGGGTCTACAGAGTCCCATCTGCCCAA AGGTCTTGAAGCTTGACAGGATGTTTTCGATTACTCAGTCTCCCAGGGCA CTACTGGTCCGTAGGATTCGATTGGTCGGGGTAGGAGAGTTAAACAACAT TTAAACAGAGTTCTCTCAAAAATGTCTAAAGGGATTGTAGGTAGATAACAT CCAATCACTGTTTGCACTTATCTGAAATCTTCCCTCTTGGCTGCCCCCAG GTATTTACTGTGGAGAACATTGCATAGGAATGTCTGGAAAAAGCTTCTACA ACTTGTTACAGCCTTCACATTTGTAGAAGCTTT 64 COX8- ATGTCCGTCCTGACGCGCCTGCTGCTGCGGGGCTTGACACGGCTCGGCT ND6- CGGCGGCTCCAGTGCGGCGCGCCAGAATCCATTCGTTGATGATGTATGC 3'UTR* TTTGTTTCTGTTGAGTGTGGGTTTAGTAATGGGGTTTGTGGGGTTTTCTTC TAAGCCTTCTCCTATTTATGGGGGTTTAGTATTGATTGTTAGCGGTGTGGT CGGGTGTGTTATTATTCTGAATTTTGGGGGAGGTTATATGGGTTTAATGGT TTTTTTAATTTATTTAGGGGGAATGATGGTTGTCTTTGGATATACTACAGC GATGGCTATTGAGGAGTATCCTGAGGCATGGGGGTCAGGGGTTGAGGTC TTGGTGAGTGTTTTAGTGGGGTTAGCGATGGAGGTAGGATTGGTGCTGT GGGTGAAAGAGTATGATGGGGTGGTGGTTGTGGTAAACTTTAATAGTGTA GGAAGCTGGATGATTTATGAAGGAGAGGGGTCAGGGTTGATTCGGGAGG ATCCTATTGGTGCGGGGGCTTTGTATGATTATGGGCGTTGGTTAGTAGTA GTTACTGGTTGGACATTGTTTGTTGGTGTATATATTGTAATTGAGATTGCT CGGGGGAATTAGGAGCACTGGGACGCCCACCGCCCCTTTCCCTCCGCTG CCAGGCGAGCATGTTGTGGTAATTCTGGAACACAAGAAGAGAAATTGCTG GGTTTAGAACAAGATTATAAACGAATTCGGTGCTCAGTGATCACTTGACA GTTTTTTTTTTTTTTAAATATTACCCAAAATGCTCCCCAAATAAGAAATGCA TCAGCTCAGTCAGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGGTC TTTTATACATCTCTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCTCA CATGGGGGTACACATACACAGCTTCCTCTTTTGGTTCCATCCTTACCACC ACACCACACGCACACTCCACATGCCCAGCAGAGTGGCACTTGGTGGCCA GAAAGTGTGAGCCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGGTC CCTCAAAGGCCTCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCCTG CATTTTTGGTTTTCCCCACCCCACACATTCTCAACCATAGTCCTTCTAACA ATACCAATAGCTAGGACCCGGCTGCTGTGCACTGGGACTGGGGATTCCA CATGTTTGCCTTGGGAGTCTCAAGCTGGACTGCCA 65 COX8- ATGTCCGTCCTGACGCGCCTGCTGCTGCGGGGCTTGACACGGCTCGGCT opt_ND6- CGGCGGCTCCAGTGCGGCGCGCCAGAATCCATTCGTTGATGATGTACGC 3'UTR CCTGTTCCTGCTGAGCGTGGGCCTGGTGATGGGCTTCGTGGGCTTCAGC AGCAAGCCCAGCCCCATCTACGGCGGCCTGGTGCTGATCGTGAGCGGC GTGGTGGGCTGCGTGATCATCCTGAACTTCGGCGGCGGCTACATGGGCC TGATGGTGTTCCTGATCTACCTGGGCGGCATGATGGTGGTGTTCGGCTA CACCACCGCCATGGCCATCGAGGAGTACCCCGAGGCCTGGGGCAGCGG CGTGGAGGTGCTGGTGAGCGTGCTGGTGGGCCTGGCCATGGAGGTGGG CCTGGTGCTGTGGGTGAAGGAGTACGACGGCGTGGTGGTGGTGGTGAA CTTCAACAGCGTGGGCAGCTGGATGATCTACGAGGGCGAGGGCAGCGG CCTGATCCGCGAGGACCCCATCGGCGCCGGCGCCCTGTACGACTACGG CCGCTGGCTGGTGGTGGTGACCGGCTGGACCCTGTTCGTGGGCGTGTA CATCGTGATCGAGATCGCCCGCGGCAACTAAGAGCACTGGGACGCCCAC CGCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAATTCTGGAA CACAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAACGAATTCGG TGCTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTACCCAAAATG CTCCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACAAAAAAGGAA TTATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACCCCACCCT CTATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACACAGCTTCCTCT TTTGGTTCCATCCTTACCACCACACCACACGCACACTCCACATGCCCAGC AGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCTGCTGTCT GTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACCCCCTTCC TTGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCCACACATT CTCAACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCGGCTGCTGT GCACTGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCAAGCTGG ACTGCCAGCCCCTGTCCTCCCTTCACCCCCATTGCGTATGAGCATTTCAG AACTCCAAGGAGTCACAGGCATCTTTATAGTTCACGTTAACATATAGACAC TGTTGGAAGCAGTTCCTTCTAAAAGGGTAGCCCTGGACTTAATACCAGCC GGATACCTCTGGCCCCCACCCCATTACTGTACCTCTGGAGTCACTACTGT GGGTCGCCACTCCTCTGCTACACAGCACGGCTTTTTCAAGGCTGTATTGA GAAGGGAAGTTAGGAAGAAGGGTGTGCTGGGCTAACCAGCCCACAGAG CTCACATTCCTGTCCCTTGGGTGAAAAATACATGTCCATCCTGATATCTCC TGAATTCAGAAATTAGCCTCCACATGTGCAATGGCTTTAAGAGCCAGAAG CAGGGTTCTGGGAATTTTGCAAGTTACCTGTGGCCAGGTGTGGTCTCGGT TACCAAATACGGTTACCTGCAGCTTTTTAGTCCTTTGTGCTCCCACGGGT CTACAGAGTCCCATCTGCCCAAAGGTCTTGAAGCTTGACAGGATGTTTTC GATTACTCAGTCTCCCAGGGCACTACTGGTCCGTAGGATTCGATTGGTCG GGGTAGGAGAGTTAAACAACATTTAAACAGAGTTCTCTCAAAAATGTCTAA AGGGATTGTAGGTAGATAACATCCAATCACTGTTTGCACTTATCTGAAATC TTCCCTCTTGGCTGCCCCCAGGTATTTACTGTGGAGAACATTGCATAGGA ATGTCTGGAAAAAGCTTCTACAACTTGTTACAGCCTTCACATTTGTAGAAG CTTT 66 COX8- ATGTCCGTCCTGACGCGCCTGCTGCTGCGGGGCTTGACACGGCTCGGCT opt_ND6- CGGCGGCTCCAGTGCGGCGCGCCAGAATCCATTCGTTGATGATGTACGC 3'UTR* CCTGTTCCTGCTGAGCGTGGGCCTGGTGATGGGCTTCGTGGGCTTCAGC AGCAAGCCCAGCCCCATCTACGGCGGCCTGGTGCTGATCGTGAGCGGC GTGGTGGGCTGCGTGATCATCCTGAACTTCGGCGGCGGCTACATGGGCC TGATGGTGTTCCTGATCTACCTGGGCGGCATGATGGTGGTGTTCGGCTA CACCACCGCCATGGCCATCGAGGAGTACCCCGAGGCCTGGGGCAGCGG CGTGGAGGTGCTGGTGAGCGTGCTGGTGGGCCTGGCCATGGAGGTGGG CCTGGTGCTGTGGGTGAAGGAGTACGACGGCGTGGTGGTGGTGGTGAA CTTCAACAGCGTGGGCAGCTGGATGATCTACGAGGGCGAGGGCAGCGG CCTGATCCGCGAGGACCCCATCGGCGCCGGCGCCCTGTACGACTACGG CCGCTGGCTGGTGGTGGTGACCGGCTGGACCCTGTTCGTGGGCGTGTA CATCGTGATCGAGATCGCCCGCGGCAACTAAGAGCACTGGGACGCCCAC CGCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAATTCTGGAA
CACAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAACGAATTCGG TGCTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTACCCAAAATG CTCCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACAAAAAAGGAA TTATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACCCCACCCT CTATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACACAGCTTCCTCT TTTGGTTCCATCCTTACCACCACACCACACGCACACTCCACATGCCCAGC AGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCTGCTGTCT GTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACCCCCTTCC TTGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCCACACATT CTCAACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCGGCTGCTGT GCACTGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCAAGCTGG ACTGCCA 67 COX8- ATGTCCGTCCTGACGCGCCTGCTGCTGCGGGGCTTGACACGGCTCGGCT ND1- CGGCGGCTCCAGTGCGGCGCGCCAGAATCCATTCGTTGATGCCCATGGC 3'UTR CAACCTCCTACTCCTCATTGTACCCATTCTAATCGCAATGGCATTCCTAAT GCTTACCGAACGAAAAATTCTAGGCTATATGCAACTACGCAAAGGCCCCA ACGTTGTAGGCCCCTACGGGCTACTACAACCCTTCGCTGACGCCATGAAA CTCTTCACCAAAGAGCCCCTAAAACCCGCCACATCTACCATCACCCTCTA CATCACCGCCCCGACCTTAGCTCTCACCATCGCTCTTCTACTATGGACCC CCCTCCCCATGCCCAACCCCCTGGTCAACCTCAACCTAGGCCTCCTATTT ATTCTAGCCACCTCTAGCCTAGCCGTTTACTCAATCCTCTGGTCAGGGTG GGCATCAAACTCAAACTACGCCCTGATCGGCGCACTGCGAGCAGTAGCC CAAACAATCTCATATGAAGTCACCCTAGCCATCATTCTACTATCAACATTA CTAATGAGTGGCTCCTTTAACCTCTCCACCCTTATCACAACACAAGAACAC CTCTGGTTACTCCTGCCATCATGGCCCTTGGCCATGATGTGGTTTATCTC CACACTAGCAGAGACCAACCGAACCCCCTTCGACCTTGCCGAAGGGGAG TCCGAACTAGTCTCAGGCTTCAACATCGAATACGCCGCAGGCCCCTTCGC CCTATTCTTCATGGCCGAATACACAAACATTATTATGATGAACACCCTCAC CACTACAATCTTCCTAGGAACAACATATGACGCACTCTCCCCTGAACTCTA CACAACATATTTTGTCACCAAGACCCTACTTCTAACCTCCCTGTTCTTATG GATTCGAACAGCATACCCCCGATTCCGCTACGACCAACTCATGCACCTCC TATGGAAAAACTTCCTACCACTCACCCTAGCATTACTTATGTGGTATGTCT CCATGCCCATTACAATCTCCAGCATTCCCCCTCAAACCTAAGAGCACTGG GACGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTA ATTCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAAC GAATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTAC CCAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACAA AAAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACC CCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACACAG CTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGCACACTCCACAT GCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCT GCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACC CCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCC ACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCGG CTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCA AGCTGGACTGCCAGCCCCTGTCCTCCCTTCACCCCCATTGCGTATGAGC ATTTCAGAACTCCAAGGAGTCACAGGCATCTTTATAGTTCACGTTAACATA TAGACACTGTTGGAAGCAGTTCCTTCTAAAAGGGTAGCCCTGGACTTAAT ACCAGCCGGATACCTCTGGCCCCCACCCCATTACTGTACCTCTGGAGTCA CTACTGTGGGTCGCCACTCCTCTGCTACACAGCACGGCTTTTTCAAGGCT GTATTGAGAAGGGAAGTTAGGAAGAAGGGTGTGCTGGGCTAACCAGCCC ACAGAGCTCACATTCCTGTCCCTTGGGTGAAAAATACATGTCCATCCTGA TATCTCCTGAATTCAGAAATTAGCCTCCACATGTGCAATGGCTTTAAGAGC CAGAAGCAGGGTTCTGGGAATTTTGCAAGTTACCTGTGGCCAGGTGTGG TCTCGGTTACCAAATACGGTTACCTGCAGCTTTTTAGTCCTTTGTGCTCCC ACGGGTCTACAGAGTCCCATCTGCCCAAAGGTCTTGAAGCTTGACAGGAT GTTTTCGATTACTCAGTCTCCCAGGGCACTACTGGTCCGTAGGATTCGAT TGGTCGGGGTAGGAGAGTTAAACAACATTTAAACAGAGTTCTCTCAAAAA TGTCTAAAGGGATTGTAGGTAGATAACATCCAATCACTGTTTGCACTTATC TGAAATCTTCCCTCTTGGCTGCCCCCAGGTATTTACTGTGGAGAACATTG CATAGGAATGTCTGGAAAAAGCTTCTACAACTTGTTACAGCCTTCACATTT GTAGAAGCTTT 68 COX8- ATGTCCGTCCTGACGCGCCTGCTGCTGCGGGGCTTGACACGGCTCGGCT ND1- CGGCGGCTCCAGTGCGGCGCGCCAGAATCCATTCGTTGATGCCCATGGC 3'UTR* CAACCTCCTACTCCTCATTGTACCCATTCTAATCGCAATGGCATTCCTAAT GCTTACCGAACGAAAAATTCTAGGCTATATGCAACTACGCAAAGGCCCCA ACGTTGTAGGCCCCTACGGGCTACTACAACCCTTCGCTGACGCCATGAAA CTCTTCACCAAAGAGCCCCTAAAACCCGCCACATCTACCATCACCCTCTA CATCACCGCCCCGACCTTAGCTCTCACCATCGCTCTTCTACTATGGACCC CCCTCCCCATGCCCAACCCCCTGGTCAACCTCAACCTAGGCCTCCTATTT ATTCTAGCCACCTCTAGCCTAGCCGTTTACTCAATCCTCTGGTCAGGGTG GGCATCAAACTCAAACTACGCCCTGATCGGCGCACTGCGAGCAGTAGCC CAAACAATCTCATATGAAGTCACCCTAGCCATCATTCTACTATCAACATTA CTAATGAGTGGCTCCTTTAACCTCTCCACCCTTATCACAACACAAGAACAC CTCTGGTTACTCCTGCCATCATGGCCCTTGGCCATGATGTGGTTTATCTC CACACTAGCAGAGACCAACCGAACCCCCTTCGACCTTGCCGAAGGGGAG TCCGAACTAGTCTCAGGCTTCAACATCGAATACGCCGCAGGCCCCTTCGC CCTATTCTTCATGGCCGAATACACAAACATTATTATGATGAACACCCTCAC CACTACAATCTTCCTAGGAACAACATATGACGCACTCTCCCCTGAACTCTA CACAACATATTTTGTCACCAAGACCCTACTTCTAACCTCCCTGTTCTTATG GATTCGAACAGCATACCCCCGATTCCGCTACGACCAACTCATGCACCTCC TATGGAAAAACTTCCTACCACTCACCCTAGCATTACTTATGTGGTATGTCT CCATGCCCATTACAATCTCCAGCATTCCCCCTCAAACCTAAGAGCACTGG GACGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTA ATTCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAAC GAATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTAC CCAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACAA AAAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACC CCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACACAG CTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGCACACTCCACAT GCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCT GCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACC CCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCC ACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCGG CTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCA AGCTGGACTGCCA 69 COX8- ATGTCCGTCCTGACGCGCCTGCTGCTGCGGGGCTTGACACGGCTCGGCT opt_ND1- CGGCGGCTCCAGTGCGGCGCGCCAGAATCCATTCGTTGATGCCCATGGC 3'UTR CAACCTGCTGCTGCTGATCGTGCCCATCCTGATCGCCATGGCCTTCCTGA TGCTGACCGAGCGCAAGATCCTGGGCTACATGCAGCTGCGCAAGGGCCC CAACGTGGTGGGCCCCTACGGCCTGCTGCAGCCCTTCGCCGACGCCAT GAAGCTGTTCACCAAGGAGCCCCTGAAGCCCGCCACCAGCACCATCACC CTGTACATCACCGCCCCCACCCTGGCCCTGACCATCGCCCTGCTGCTGT GGACCCCCCTGCCCATGCCCAACCCCCTGGTGAACCTGAACCTGGGCCT GCTGTTCATCCTGGCCACCAGCAGCCTGGCCGTGTACAGCATCCTGTGG AGCGGCTGGGCCAGCAACAGCAACTACGCCCTGATCGGCGCCCTGCGC GCCGTGGCCCAGACCATCAGCTACGAGGTGACCCTGGCCATCATCCTGC TGAGCACCCTGCTGATGAGCGGCAGCTTCAACCTGAGCACCCTGATCAC CACCCAGGAGCACCTGTGGCTGCTGCTGCCCAGCTGGCCCCTGGCCAT GATGTGGTTCATCAGCACCCTGGCCGAGACCAACCGCACCCCCTTCGAC CTGGCCGAGGGCGAGAGCGAGCTGGTGAGCGGCTTCAACATCGAGTAC GCCGCCGGCCCCTTCGCCCTGTTCTTCATGGCCGAGTACACCAACATCA TCATGATGAACACCCTGACCACCACCATCTTCCTGGGCACCACCTACGAC GCCCTGAGCCCCGAGCTGTACACCACCTACTTCGTGACCAAGACCCTGC TGCTGACCAGCCTGTTCCTGTGGATCCGCACCGCCTACCCCCGCTTCCG CTACGACCAGCTGATGCACCTGCTGTGGAAGAACTTCCTGCCCCTGACC CTGGCCCTGCTGATGTGGTACGTGAGCATGCCCATCACCATCAGCAGCA TCCCCCCCCAGACCTAAGAGCACTGGGACGCCCACCGCCCCTTTCCCTC CGCTGCCAGGCGAGCATGTTGTGGTAATTCTGGAACACAAGAAGAGAAAT TGCTGGGTTTAGAACAAGATTATAAACGAATTCGGTGCTCAGTGATCACTT GACAGTTTTTTTTTTTTTTAAATATTACCCAAAATGCTCCCCAAATAAGAAA TGCATCAGCTCAGTCAGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAG GGTCTTTTATACATCTCTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCT CCTCACATGGGGGTACACATACACAGCTTCCTCTTTTGGTTCCATCCTTAC CACCACACCACACGCACACTCCACATGCCCAGCAGAGTGGCACTTGGTG GCCAGAAAGTGTGAGCCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCA GGTCCCTCAAAGGCCTCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGG CCTGCATTTTTGGTTTTCCCCACCCCACACATTCTCAACCATAGTCCTTCT AACAATACCAATAGCTAGGACCCGGCTGCTGTGCACTGGGACTGGGGAT TCCACATGTTTGCCTTGGGAGTCTCAAGCTGGACTGCCAGCCCCTGTCCT CCCTTCACCCCCATTGCGTATGAGCATTTCAGAACTCCAAGGAGTCACAG GCATCTTTATAGTTCACGTTAACATATAGACACTGTTGGAAGCAGTTCCTT CTAAAAGGGTAGCCCTGGACTTAATACCAGCCGGATACCTCTGGCCCCC ACCCCATTACTGTACCTCTGGAGTCACTACTGTGGGTCGCCACTCCTCTG CTACACAGCACGGCTTTTTCAAGGCTGTATTGAGAAGGGAAGTTAGGAAG AAGGGTGTGCTGGGCTAACCAGCCCACAGAGCTCACATTCCTGTCCCTT GGGTGAAAAATACATGTCCATCCTGATATCTCCTGAATTCAGAAATTAGCC TCCACATGTGCAATGGCTTTAAGAGCCAGAAGCAGGGTTCTGGGAATTTT GCAAGTTACCTGTGGCCAGGTGTGGTCTCGGTTACCAAATACGGTTACCT GCAGCTTTTTAGTCCTTTGTGCTCCCACGGGTCTACAGAGTCCCATCTGC CCAAAGGTCTTGAAGCTTGACAGGATGTTTTCGATTACTCAGTCTCCCAG GGCACTACTGGTCCGTAGGATTCGATTGGTCGGGGTAGGAGAGTTAAAC AACATTTAAACAGAGTTCTCTCAAAAATGTCTAAAGGGATTGTAGGTAGAT AACATCCAATCACTGTTTGCACTTATCTGAAATCTTCCCTCTTGGCTGCCC CCAGGTATTTACTGTGGAGAACATTGCATAGGAATGTCTGGAAAAAGCTT CTACAACTTGTTACAGCCTTCACATTTGTAGAAGCTTT 70 COX8- ATGTCCGTCCTGACGCGCCTGCTGCTGCGGGGCTTGACACGGCTCGGCT opt_ND1- CGGCGGCTCCAGTGCGGCGCGCCAGAATCCATTCGTTGATGCCCATGGC 3'UTR* CAACCTGCTGCTGCTGATCGTGCCCATCCTGATCGCCATGGCCTTCCTGA TGCTGACCGAGCGCAAGATCCTGGGCTACATGCAGCTGCGCAAGGGCCC CAACGTGGTGGGCCCCTACGGCCTGCTGCAGCCCTTCGCCGACGCCAT GAAGCTGTTCACCAAGGAGCCCCTGAAGCCCGCCACCAGCACCATCACC CTGTACATCACCGCCCCCACCCTGGCCCTGACCATCGCCCTGCTGCTGT GGACCCCCCTGCCCATGCCCAACCCCCTGGTGAACCTGAACCTGGGCCT GCTGTTCATCCTGGCCACCAGCAGCCTGGCCGTGTACAGCATCCTGTGG AGCGGCTGGGCCAGCAACAGCAACTACGCCCTGATCGGCGCCCTGCGC GCCGTGGCCCAGACCATCAGCTACGAGGTGACCCTGGCCATCATCCTGC TGAGCACCCTGCTGATGAGCGGCAGCTTCAACCTGAGCACCCTGATCAC CACCCAGGAGCACCTGTGGCTGCTGCTGCCCAGCTGGCCCCTGGCCAT GATGTGGTTCATCAGCACCCTGGCCGAGACCAACCGCACCCCCTTCGAC CTGGCCGAGGGCGAGAGCGAGCTGGTGAGCGGCTTCAACATCGAGTAC GCCGCCGGCCCCTTCGCCCTGTTCTTCATGGCCGAGTACACCAACATCA TCATGATGAACACCCTGACCACCACCATCTTCCTGGGCACCACCTACGAC GCCCTGAGCCCCGAGCTGTACACCACCTACTTCGTGACCAAGACCCTGC TGCTGACCAGCCTGTTCCTGTGGATCCGCACCGCCTACCCCCGCTTCCG CTACGACCAGCTGATGCACCTGCTGTGGAAGAACTTCCTGCCCCTGACC CTGGCCCTGCTGATGTGGTACGTGAGCATGCCCATCACCATCAGCAGCA TCCCCCCCCAGACCTAAGAGCACTGGGACGCCCACCGCCCCTTTCCCTC CGCTGCCAGGCGAGCATGTTGTGGTAATTCTGGAACACAAGAAGAGAAAT TGCTGGGTTTAGAACAAGATTATAAACGAATTCGGTGCTCAGTGATCACTT GACAGTTTTTTTTTTTTTTAAATATTACCCAAAATGCTCCCCAAATAAGAAA TGCATCAGCTCAGTCAGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAG GGTCTTTTATACATCTCTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCT CCTCACATGGGGGTACACATACACAGCTTCCTCTTTTGGTTCCATCCTTAC CACCACACCACACGCACACTCCACATGCCCAGCAGAGTGGCACTTGGTG GCCAGAAAGTGTGAGCCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCA GGTCCCTCAAAGGCCTCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGG CCTGCATTTTTGGTTTTCCCCACCCCACACATTCTCAACCATAGTCCTTCT AACAATACCAATAGCTAGGACCCGGCTGCTGTGCACTGGGACTGGGGAT TCCACATGTTTGCCTTGGGAGTCTCAAGCTGGACTGCCA 71 OPA1- GTGCTGCCCGCCTAGAAAGGGTGAAGTGGTTGTTTCCGTGACGGACTGA ND4- GTACGGGTGCCTGTCAGGCTCTTGCGGAAGTCCATGCGCCATTGGGAGG 3'UTR GCCTCGGCCGCGGCTCTGTGCCCTTGCTGCTGAGGGCCACTTCCTGGGT CATTCCTGGACCGGGAGCCGGGCTGGGGCTCACACGGGGGCTCCCGCG TGGCCGTCTCGGCGCCTGCGTGACCTCCCCGCCGGCGGGATGTGGCGA CTACGTCGGGCCGCTGTGGCCTGATGCTAAAACTAATCGTCCCAACAATT ATGTTACTACCACTGACATGGCTTTCCAAAAAACACATGATTTGGATCAAC ACAACCACCCACAGCCTAATTATTAGCATCATCCCTCTACTATTTTTTAAC CAAATCAACAACAACCTATTTAGCTGTTCCCCAACCTTTTCCTCCGACCCC CTAACAACCCCCCTCCTAATGCTAACTACCTGGCTCCTACCCCTCACAAT CATGGCAAGCCAACGCCACTTATCCAGTGAACCACTATCACGAAAAAAAC TCTACCTCTCTATGCTAATCTCCCTACAAATCTCCTTAATTATGACATTCAC AGCCACAGAACTAATCATGTTTTATATCTTCTTCGAAACCACACTTATCCC CACCTTGGCTATCATCACCCGATGGGGCAACCAGCCAGAACGCCTGAAC GCAGGCACATACTTCCTATTCTACACCCTAGTAGGCTCCCTTCCCCTACT CATCGCACTAATTTACACTCACAACACCCTAGGCTCACTAAACATTCTACT ACTCACTCTCACTGCCCAAGAACTATCAAACTCCTGGGCCAACAACTTAAT GTGGCTAGCTTACACAATGGCTTTTATGGTAAAGATGCCTCTTTACGGACT CCACTTATGGCTCCCTAAAGCCCATGTCGAAGCCCCCATCGCTGGGTCAA TGGTACTTGCCGCAGTACTCTTAAAACTAGGCGGCTATGGTATGATGCGC CTCACACTCATTCTCAACCCCCTGACAAAACACATGGCCTACCCCTTCCTT GTACTATCCCTATGGGGCATGATTATGACAAGCTCCATCTGCCTACGACA AACAGACCTAAAATCGCTCATTGCATACTCTTCAATCAGCCACATGGCCCT CGTAGTAACAGCCATTCTCATCCAAACCCCCTGGAGCTTCACCGGCGCA GTCATTCTCATGATCGCCCACGGGCTTACATCCTCATTACTATTCTGCCTA GCAAACTCAAACTACGAACGCACTCACAGTCGCATCATGATCCTCTCTCA AGGACTTCAAACTCTACTCCCACTAATGGCTTTTTGGTGGCTTCTAGCAAG CCTCGCTAACCTCGCCTTACCCCCCACTATTAACCTACTGGGAGAACTCT CTGTGCTAGTAACCACGTTCTCCTGGTCAAATATCACTCTCCTACTTACAG GACTCAACATGCTAGTCACAGCCCTATACTCCCTCTACATGTTTACCACAA CACAATGGGGCTCACTCACCCACCACATTAACAACATGAAACCCTCATTC ACACGAGAAAACACCCTCATGTTCATGCACCTATCCCCCATTCTCCTCCTA TCCCTCAACCCCGACATCATTACCGGGTTTTCCTCTTAAGAGCACTGGGA CGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAAT TCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAACG AATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTACC CAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACAAA AAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACC CCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACACAG CTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGCACACTCCACAT GCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCT GCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACC CCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCC ACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCGG CTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCA AGCTGGACTGCCAGCCCCTGTCCTCCCTTCACCCCCATTGCGTATGAGC ATTTCAGAACTCCAAGGAGTCACAGGCATCTTTATAGTTCACGTTAACATA TAGACACTGTTGGAAGCAGTTCCTTCTAAAAGGGTAGCCCTGGACTTAAT ACCAGCCGGATACCTCTGGCCCCCACCCCATTACTGTACCTCTGGAGTCA CTACTGTGGGTCGCCACTCCTCTGCTACACAGCACGGCTTTTTCAAGGCT GTATTGAGAAGGGAAGTTAGGAAGAAGGGTGTGCTGGGCTAACCAGCCC ACAGAGCTCACATTCCTGTCCCTTGGGTGAAAAATACATGTCCATCCTGA TATCTCCTGAATTCAGAAATTAGCCTCCACATGTGCAATGGCTTTAAGAGC CAGAAGCAGGGTTCTGGGAATTTTGCAAGTTACCTGTGGCCAGGTGTGG TCTCGGTTACCAAATACGGTTACCTGCAGCTTTTTAGTCCTTTGTGCTCCC ACGGGTCTACAGAGTCCCATCTGCCCAAAGGTCTTGAAGCTTGACAGGAT GTTTTCGATTACTCAGTCTCCCAGGGCACTACTGGTCCGTAGGATTCGAT TGGTCGGGGTAGGAGAGTTAAACAACATTTAAACAGAGTTCTCTCAAAAA TGTCTAAAGGGATTGTAGGTAGATAACATCCAATCACTGTTTGCACTTATC TGAAATCTTCCCTCTTGGCTGCCCCCAGGTATTTACTGTGGAGAACATTG CATAGGAATGTCTGGAAAAAGCTTCTACAACTTGTTACAGCCTTCACATTT GTAGAAGCTTT 72 OPA1- GTGCTGCCCGCCTAGAAAGGGTGAAGTGGTTGTTTCCGTGACGGACTGA ND4- GTACGGGTGCCTGTCAGGCTCTTGCGGAAGTCCATGCGCCATTGGGAGG 3'UTR* GCCTCGGCCGCGGCTCTGTGCCCTTGCTGCTGAGGGCCACTTCCTGGGT
CATTCCTGGACCGGGAGCCGGGCTGGGGCTCACACGGGGGCTCCCGCG TGGCCGTCTCGGCGCCTGCGTGACCTCCCCGCCGGCGGGATGTGGCGA CTACGTCGGGCCGCTGTGGCCTGATGCTAAAACTAATCGTCCCAACAATT ATGTTACTACCACTGACATGGCTTTCCAAAAAACACATGATTTGGATCAAC ACAACCACCCACAGCCTAATTATTAGCATCATCCCTCTACTATTTTTTAAC CAAATCAACAACAACCTATTTAGCTGTTCCCCAACCTTTTCCTCCGACCCC CTAACAACCCCCCTCCTAATGCTAACTACCTGGCTCCTACCCCTCACAAT CATGGCAAGCCAACGCCACTTATCCAGTGAACCACTATCACGAAAAAAAC TCTACCTCTCTATGCTAATCTCCCTACAAATCTCCTTAATTATGACATTCAC AGCCACAGAACTAATCATGTTTTATATCTTCTTCGAAACCACACTTATCCC CACCTTGGCTATCATCACCCGATGGGGCAACCAGCCAGAACGCCTGAAC GCAGGCACATACTTCCTATTCTACACCCTAGTAGGCTCCCTTCCCCTACT CATCGCACTAATTTACACTCACAACACCCTAGGCTCACTAAACATTCTACT ACTCACTCTCACTGCCCAAGAACTATCAAACTCCTGGGCCAACAACTTAAT GTGGCTAGCTTACACAATGGCTTTTATGGTAAAGATGCCTCTTTACGGACT CCACTTATGGCTCCCTAAAGCCCATGTCGAAGCCCCCATCGCTGGGTCAA TGGTACTTGCCGCAGTACTCTTAAAACTAGGCGGCTATGGTATGATGCGC CTCACACTCATTCTCAACCCCCTGACAAAACACATGGCCTACCCCTTCCTT GTACTATCCCTATGGGGCATGATTATGACAAGCTCCATCTGCCTACGACA AACAGACCTAAAATCGCTCATTGCATACTCTTCAATCAGCCACATGGCCCT CGTAGTAACAGCCATTCTCATCCAAACCCCCTGGAGCTTCACCGGCGCA GTCATTCTCATGATCGCCCACGGGCTTACATCCTCATTACTATTCTGCCTA GCAAACTCAAACTACGAACGCACTCACAGTCGCATCATGATCCTCTCTCA AGGACTTCAAACTCTACTCCCACTAATGGCTTTTTGGTGGCTTCTAGCAAG CCTCGCTAACCTCGCCTTACCCCCCACTATTAACCTACTGGGAGAACTCT CTGTGCTAGTAACCACGTTCTCCTGGTCAAATATCACTCTCCTACTTACAG GACTCAACATGCTAGTCACAGCCCTATACTCCCTCTACATGTTTACCACAA CACAATGGGGCTCACTCACCCACCACATTAACAACATGAAACCCTCATTC ACACGAGAAAACACCCTCATGTTCATGCACCTATCCCCCATTCTCCTCCTA TCCCTCAACCCCGACATCATTACCGGGTTTTCCTCTTAAGAGCACTGGGA CGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAAT TCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAACG AATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTACC CAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACAAA AAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACC CCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTACACATACACAG CTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGCACACTCCACAT GCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCT GCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACC CCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCC ACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCTAGGACCCGG CTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCA AGCTGGACTGCCA 73 OPA1- GTGCTGCCCGCCTAGAAAGGGTGAAGTGGTTGTTTCCGTGACGGACTGA opt_ND4- GTACGGGTGCCTGTCAGGCTCTTGCGGAAGTCCATGCGCCATTGGGAGG 3'UTR GCCTCGGCCGCGGCTCTGTGCCCTTGCTGCTGAGGGCCACTTCCTGGGT CATTCCTGGACCGGGAGCCGGGCTGGGGCTCACACGGGGGCTCCCGCG TGGCCGTCTCGGCGCCTGCGTGACCTCCCCGCCGGCGGGATGTGGCGA CTACGTCGGGCCGCTGTGGCCTGATGCTGAAGCTGATCGTGCCCACCAT CATGCTGCTGCCTCTGACCTGGCTGAGCAAGAAACACATGATCTGGATCA ACACCACCACGCACAGCCTGATCATCAGCATCATCCCTCTGCTGTTCTTC AACCAGATCAACAACAACCTGTTCAGCTGCAGCCCCACCTTCAGCAGCGA CCCTCTGACAACACCTCTGCTGATGCTGACCACCTGGCTGCTGCCCCTCA CAATCATGGCCTCTCAGAGACACCTGAGCAGCGAGCCCCTGAGCCGGAA GAAACTGTACCTGAGCATGCTGATCTCCCTGCAGATCTCTCTGATCATGA CCTTCACCGCCACCGAGCTGATCATGTTCTACATCTTTTTCGAGACAACG CTGATCCCCACACTGGCCATCATCACCAGATGGGGCAACCAGCCTGAGA GACTGAACGCCGGCACCTACTTTCTGTTCTACACCCTCGTGGGCAGCCT GCCACTGCTGATTGCCCTGATCTACACCCACAACACCCTGGGCTCCCTGA ACATCCTGCTGCTGACACTGACAGCCCAAGAGCTGAGCAACAGCTGGGC CAACAATCTGATGTGGCTGGCCTACACAATGGCCTTCATGGTCAAGATGC CCCTGTACGGCCTGCACCTGTGGCTGCCTAAAGCTCATGTGGAAGCCCC TATCGCCGGCTCTATGGTGCTGGCTGCAGTGCTGCTGAAACTCGGCGGC TACGGCATGATGCGGCTGACCCTGATTCTGAATCCCCTGACCAAGCACAT GGCCTATCCATTTCTGGTGCTGAGCCTGTGGGGCATGATTATGACCAGCA GCATCTGCCTGCGGCAGACCGATCTGAAGTCCCTGATCGCCTACAGCTC CATCAGCCACATGGCCCTGGTGGTCACCGCCATCCTGATTCAGACCCCTT GGAGCTTTACAGGCGCCGTGATCCTGATGATTGCCCACGGCCTGACAAG CAGCCTGCTGTTTTGTCTGGCCAACAGCAACTACGAGCGGACCCACAGC AGAATCATGATCCTGTCTCAGGGCCTGCAGACCCTCCTGCCTCTTATGGC TTTTTGGTGGCTGCTGGCCTCTCTGGCCAATCTGGCACTGCCTCCTACCA TCAATCTGCTGGGCGAGCTGAGCGTGCTGGTCACCACATTCAGCTGGTC CAATATCACCCTGCTGCTCACCGGCCTGAACATGCTGGTTACAGCCCTGT ACTCCCTGTACATGTTCACCACCACACAGTGGGGAAGCCTGACACACCAC ATCAACAATATGAAGCCCAGCTTCACCCGCGAGAACACCCTGATGTTCAT GCATCTGAGCCCCATTCTGCTGCTGTCCCTGAATCCTGATATCATCACCG GCTTCTCCAGCTGAGAGCACTGGGACGCCCACCGCCCCTTTCCCTCCGC TGCCAGGCGAGCATGTTGTGGTAATTCTGGAACACAAGAAGAGAAATTGC TGGGTTTAGAACAAGATTATAAACGAATTCGGTGCTCAGTGATCACTTGAC AGTTTTTTTTTTTTTTAAATATTACCCAAAATGCTCCCCAAATAAGAAATGC ATCAGCTCAGTCAGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGGT CTTTTATACATCTCTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCTC ACATGGGGGTACACATACACAGCTTCCTCTTTTGGTTCCATCCTTACCAC CACACCACACGCACACTCCACATGCCCAGCAGAGTGGCACTTGGTGGCC AGAAAGTGTGAGCCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGGT CCCTCAAAGGCCTCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCCT GCATTTTTGGTTTTCCCCACCCCACACATTCTCAACCATAGTCCTTCTAAC AATACCAATAGCTAGGACCCGGCTGCTGTGCACTGGGACTGGGGATTCC ACATGTTTGCCTTGGGAGTCTCAAGCTGGACTGCCAGCCCCTGTCCTCCC TTCACCCCCATTGCGTATGAGCATTTCAGAACTCCAAGGAGTCACAGGCA TCTTTATAGTTCACGTTAACATATAGACACTGTTGGAAGCAGTTCCTTCTA AAAGGGTAGCCCTGGACTTAATACCAGCCGGATACCTCTGGCCCCCACC CCATTACTGTACCTCTGGAGTCACTACTGTGGGTCGCCACTCCTCTGCTA CACAGCACGGCTTTTTCAAGGCTGTATTGAGAAGGGAAGTTAGGAAGAAG GGTGTGCTGGGCTAACCAGCCCACAGAGCTCACATTCCTGTCCCTTGGG TGAAAAATACATGTCCATCCTGATATCTCCTGAATTCAGAAATTAGCCTCC ACATGTGCAATGGCTTTAAGAGCCAGAAGCAGGGTTCTGGGAATTTTGCA AGTTACCTGTGGCCAGGTGTGGTCTCGGTTACCAAATACGGTTACCTGCA GCTTTTTAGTCCTTTGTGCTCCCACGGGTCTACAGAGTCCCATCTGCCCA AAGGTCTTGAAGCTTGACAGGATGTTTTCGATTACTCAGTCTCCCAGGGC ACTACTGGTCCGTAGGATTCGATTGGTCGGGGTAGGAGAGTTAAACAACA TTTAAACAGAGTTCTCTCAAAAATGTCTAAAGGGATTGTAGGTAGATAACA TCCAATCACTGTTTGCACTTATCTGAAATCTTCCCTCTTGGCTGCCCCCAG GTATTTACTGTGGAGAACATTGCATAGGAATGTCTGGAAAAAGCTTCTACA ACTTGTTACAGCCTTCACATTTGTAGAAGCTTT 74 OPA1- GTGCTGCCCGCCTAGAAAGGGTGAAGTGGTTGTTTCCGTGACGGACTGA opt_ND4- GTACGGGTGCCTGTCAGGCTCTTGCGGAAGTCCATGCGCCATTGGGAGG 3'UTR* GCCTCGGCCGCGGCTCTGTGCCCTTGCTGCTGAGGGCCACTTCCTGGGT CATTCCTGGACCGGGAGCCGGGCTGGGGCTCACACGGGGGCTCCCGCG TGGCCGTCTCGGCGCCTGCGTGACCTCCCCGCCGGCGGGATGTGGCGA CTACGTCGGGCCGCTGTGGCCTGATGCTGAAGCTGATCGTGCCCACCAT CATGCTGCTGCCTCTGACCTGGCTGAGCAAGAAACACATGATCTGGATCA ACACCACCACGCACAGCCTGATCATCAGCATCATCCCTCTGCTGTTCTTC AACCAGATCAACAACAACCTGTTCAGCTGCAGCCCCACCTTCAGCAGCGA CCCTCTGACAACACCTCTGCTGATGCTGACCACCTGGCTGCTGCCCCTCA CAATCATGGCCTCTCAGAGACACCTGAGCAGCGAGCCCCTGAGCCGGAA GAAACTGTACCTGAGCATGCTGATCTCCCTGCAGATCTCTCTGATCATGA CCTTCACCGCCACCGAGCTGATCATGTTCTACATCTTTTTCGAGACAACG CTGATCCCCACACTGGCCATCATCACCAGATGGGGCAACCAGCCTGAGA GACTGAACGCCGGCACCTACTTTCTGTTCTACACCCTCGTGGGCAGCCT GCCACTGCTGATTGCCCTGATCTACACCCACAACACCCTGGGCTCCCTGA ACATCCTGCTGCTGACACTGACAGCCCAAGAGCTGAGCAACAGCTGGGC CAACAATCTGATGTGGCTGGCCTACACAATGGCCTTCATGGTCAAGATGC CCCTGTACGGCCTGCACCTGTGGCTGCCTAAAGCTCATGTGGAAGCCCC TATCGCCGGCTCTATGGTGCTGGCTGCAGTGCTGCTGAAACTCGGCGGC TACGGCATGATGCGGCTGACCCTGATTCTGAATCCCCTGACCAAGCACAT GGCCTATCCATTTCTGGTGCTGAGCCTGTGGGGCATGATTATGACCAGCA GCATCTGCCTGCGGCAGACCGATCTGAAGTCCCTGATCGCCTACAGCTC CATCAGCCACATGGCCCTGGTGGTCACCGCCATCCTGATTCAGACCCCTT GGAGCTTTACAGGCGCCGTGATCCTGATGATTGCCCACGGCCTGACAAG CAGCCTGCTGTTTTGTCTGGCCAACAGCAACTACGAGCGGACCCACAGC AGAATCATGATCCTGTCTCAGGGCCTGCAGACCCTCCTGCCTCTTATGGC TTTTTGGTGGCTGCTGGCCTCTCTGGCCAATCTGGCACTGCCTCCTACCA TCAATCTGCTGGGCGAGCTGAGCGTGCTGGTCACCACATTCAGCTGGTC CAATATCACCCTGCTGCTCACCGGCCTGAACATGCTGGTTACAGCCCTGT ACTCCCTGTACATGTTCACCACCACACAGTGGGGAAGCCTGACACACCAC ATCAACAATATGAAGCCCAGCTTCACCCGCGAGAACACCCTGATGTTCAT GCATCTGAGCCCCATTCTGCTGCTGTCCCTGAATCCTGATATCATCACCG GCTTCTCCAGCTGAGAGCACTGGGACGCCCACCGCCCCTTTCCCTCCGC TGCCAGGCGAGCATGTTGTGGTAATTCTGGAACACAAGAAGAGAAATTGC TGGGTTTAGAACAAGATTATAAACGAATTCGGTGCTCAGTGATCACTTGAC AGTTTTTTTTTTTTTTAAATATTACCCAAAATGCTCCCCAAATAAGAAATGC ATCAGCTCAGTCAGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGGT CTTTTATACATCTCTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCTC ACATGGGGGTACACATACACAGCTTCCTCTTTTGGTTCCATCCTTACCAC CACACCACACGCACACTCCACATGCCCAGCAGAGTGGCACTTGGTGGCC AGAAAGTGTGAGCCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGGT CCCTCAAAGGCCTCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCCT GCATTTTTGGTTTTCCCCACCCCACACATTCTCAACCATAGTCCTTCTAAC AATACCAATAGCTAGGACCCGGCTGCTGTGCACTGGGACTGGGGATTCC ACATGTTTGCCTTGGGAGTCTCAAGCTGGACTGCCA 75 OPA1- GTGCTGCCCGCCTAGAAAGGGTGAAGTGGTTGTTTCCGTGACGGACTGA opt_ND4*- GTACGGGTGCCTGTCAGGCTCTTGCGGAAGTCCATGCGCCATTGGGAGG 3'UTR GCCTCGGCCGCGGCTCTGTGCCCTTGCTGCTGAGGGCCACTTCCTGGGT CATTCCTGGACCGGGAGCCGGGCTGGGGCTCACACGGGGGCTCCCGCG TGGCCGTCTCGGCGCCTGCGTGACCTCCCCGCCGGCGGGATGTGGCGA CTACGTCGGGCCGCTGTGGCCTGATGCTGAAGCTGATCGTGCCCACCAT CATGCTGCTGCCCCTGACCTGGCTGAGCAAGAAGCACATGATCTGGATC AACACCACCACCCACAGCCTGATCATCAGCATCATCCCCCTGCTGTTCTT CAACCAGATCAACAACAACCTGTTCAGCTGCAGCCCCACCTTCAGCAGCG ACCCCCTGACCACCCCCCTGCTGATGCTGACCACCTGGCTGCTGCCCCT GACCATCATGGCCAGCCAGCGCCACCTGAGCAGCGAGCCCCTGAGCCG CAAGAAGCTGTACCTGAGCATGCTGATCAGCCTGCAGATCAGCCTGATCA TGACCTTCACCGCCACCGAGCTGATCATGTTCTACATCTTCTTCGAGACC ACCCTGATCCCCACCCTGGCCATCATCACCCGCTGGGGCAACCAGCCCG AGCGCCTGAACGCCGGCACCTACTTCCTGTTCTACACCCTGGTGGGCAG CCTGCCCCTGCTGATCGCCCTGATCTACACCCACAACACCCTGGGCAGC CTGAACATCCTGCTGCTGACCCTGACCGCCCAGGAGCTGAGCAACAGCT GGGCCAACAACCTGATGTGGCTGGCCTACACCATGGCCTTCATGGTGAA GATGCCCCTGTACGGCCTGCACCTGTGGCTGCCCAAGGCCCACGTGGA GGCCCCCATCGCCGGCAGCATGGTGCTGGCCGCCGTGCTGCTGAAGCT GGGCGGCTACGGCATGATGCGCCTGACCCTGATCCTGAACCCCCTGACC AAGCACATGGCCTACCCCTTCCTGGTGCTGAGCCTGTGGGGCATGATCA TGACCAGCAGCATCTGCCTGCGCCAGACCGACCTGAAGAGCCTGATCGC CTACAGCAGCATCAGCCACATGGCCCTGGTGGTGACCGCCATCCTGATC CAGACCCCCTGGAGCTTCACCGGCGCCGTGATCCTGATGATCGCCCACG GCCTGACCAGCAGCCTGCTGTTCTGCCTGGCCAACAGCAACTACGAGCG CACCCACAGCCGCATCATGATCCTGAGCCAGGGCCTGCAGACCCTGCTG CCCCTGATGGCCTTCTGGTGGCTGCTGGCCAGCCTGGCCAACCTGGCCC TGCCCCCCACCATCAACCTGCTGGGCGAGCTGAGCGTGCTGGTGACCAC CTTCAGCTGGAGCAACATCACCCTGCTGCTGACCGGCCTGAACATGCTG GTGACCGCCCTGTACAGCCTGTACATGTTCACCACCACCCAGTGGGGCA GCCTGACCCACCACATCAACAACATGAAGCCCAGCTTCACCCGCGAGAA CACCCTGATGTTCATGCACCTGAGCCCCATCCTGCTGCTGAGCCTGAACC CCGACATCATCACCGGCTTCAGCAGCTAAGAGCACTGGGACGCCCACCG CCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAATTCTGGAACAC AAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAACGAATTCGGTGC TCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTACCCAAAATGCTC CCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACAAAAAAGGAATTAT TTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACCCCACCCTCTAT TCTGTTTCTTCCTCCTCACATGGGGGTACACATACACAGCTTCCTCTTTTG GTTCCATCCTTACCACCACACCACACGCACACTCCACATGCCCAGCAGAG TGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCTGCTGTCTGTAGT TCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACCCCCTTCCTTGTG ACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCCACACATTCTCAA CCATAGTCCTTCTAACAATACCAATAGCTAGGACCCGGCTGCTGTGCACT GGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCAAGCTGGACTGC CAGCCCCTGTCCTCCCTTCACCCCCATTGCGTATGAGCATTTCAGAACTC CAAGGAGTCACAGGCATCTTTATAGTTCACGTTAACATATAGACACTGTTG GAAGCAGTTCCTTCTAAAAGGGTAGCCCTGGACTTAATACCAGCCGGATA CCTCTGGCCCCCACCCCATTACTGTACCTCTGGAGTCACTACTGTGGGTC GCCACTCCTCTGCTACACAGCACGGCTTTTTCAAGGCTGTATTGAGAAGG GAAGTTAGGAAGAAGGGTGTGCTGGGCTAACCAGCCCACAGAGCTCACA TTCCTGTCCCTTGGGTGAAAAATACATGTCCATCCTGATATCTCCTGAATT CAGAAATTAGCCTCCACATGTGCAATGGCTTTAAGAGCCAGAAGCAGGGT TCTGGGAATTTTGCAAGTTACCTGTGGCCAGGTGTGGTCTCGGTTACCAA ATACGGTTACCTGCAGCTTTTTAGTCCTTTGTGCTCCCACGGGTCTACAG AGTCCCATCTGCCCAAAGGTCTTGAAGCTTGACAGGATGTTTTCGATTAC TCAGTCTCCCAGGGCACTACTGGTCCGTAGGATTCGATTGGTCGGGGTA GGAGAGTTAAACAACATTTAAACAGAGTTCTCTCAAAAATGTCTAAAGGGA TTGTAGGTAGATAACATCCAATCACTGTTTGCACTTATCTGAAATCTTCCC TCTTGGCTGCCCCCAGGTATTTACTGTGGAGAACATTGCATAGGAATGTC TGGAAAAAGCTTCTACAACTTGTTACAGCCTTCACATTTGTAGAAGCTTT 76 OPA1- GTGCTGCCCGCCTAGAAAGGGTGAAGTGGTTGTTTCCGTGACGGACTGA opt_ND4*- GTACGGGTGCCTGTCAGGCTCTTGCGGAAGTCCATGCGCCATTGGGAGG 3'UTR* GCCTCGGCCGCGGCTCTGTGCCCTTGCTGCTGAGGGCCACTTCCTGGGT CATTCCTGGACCGGGAGCCGGGCTGGGGCTCACACGGGGGCTCCCGCG TGGCCGTCTCGGCGCCTGCGTGACCTCCCCGCCGGCGGGATGTGGCGA CTACGTCGGGCCGCTGTGGCCTGATGCTGAAGCTGATCGTGCCCACCAT CATGCTGCTGCCCCTGACCTGGCTGAGCAAGAAGCACATGATCTGGATC AACACCACCACCCACAGCCTGATCATCAGCATCATCCCCCTGCTGTTCTT CAACCAGATCAACAACAACCTGTTCAGCTGCAGCCCCACCTTCAGCAGCG ACCCCCTGACCACCCCCCTGCTGATGCTGACCACCTGGCTGCTGCCCCT GACCATCATGGCCAGCCAGCGCCACCTGAGCAGCGAGCCCCTGAGCCG CAAGAAGCTGTACCTGAGCATGCTGATCAGCCTGCAGATCAGCCTGATCA TGACCTTCACCGCCACCGAGCTGATCATGTTCTACATCTTCTTCGAGACC ACCCTGATCCCCACCCTGGCCATCATCACCCGCTGGGGCAACCAGCCCG AGCGCCTGAACGCCGGCACCTACTTCCTGTTCTACACCCTGGTGGGCAG CCTGCCCCTGCTGATCGCCCTGATCTACACCCACAACACCCTGGGCAGC CTGAACATCCTGCTGCTGACCCTGACCGCCCAGGAGCTGAGCAACAGCT GGGCCAACAACCTGATGTGGCTGGCCTACACCATGGCCTTCATGGTGAA GATGCCCCTGTACGGCCTGCACCTGTGGCTGCCCAAGGCCCACGTGGA GGCCCCCATCGCCGGCAGCATGGTGCTGGCCGCCGTGCTGCTGAAGCT GGGCGGCTACGGCATGATGCGCCTGACCCTGATCCTGAACCCCCTGACC AAGCACATGGCCTACCCCTTCCTGGTGCTGAGCCTGTGGGGCATGATCA TGACCAGCAGCATCTGCCTGCGCCAGACCGACCTGAAGAGCCTGATCGC CTACAGCAGCATCAGCCACATGGCCCTGGTGGTGACCGCCATCCTGATC CAGACCCCCTGGAGCTTCACCGGCGCCGTGATCCTGATGATCGCCCACG GCCTGACCAGCAGCCTGCTGTTCTGCCTGGCCAACAGCAACTACGAGCG CACCCACAGCCGCATCATGATCCTGAGCCAGGGCCTGCAGACCCTGCTG CCCCTGATGGCCTTCTGGTGGCTGCTGGCCAGCCTGGCCAACCTGGCCC TGCCCCCCACCATCAACCTGCTGGGCGAGCTGAGCGTGCTGGTGACCAC CTTCAGCTGGAGCAACATCACCCTGCTGCTGACCGGCCTGAACATGCTG GTGACCGCCCTGTACAGCCTGTACATGTTCACCACCACCCAGTGGGGCA GCCTGACCCACCACATCAACAACATGAAGCCCAGCTTCACCCGCGAGAA CACCCTGATGTTCATGCACCTGAGCCCCATCCTGCTGCTGAGCCTGAACC CCGACATCATCACCGGCTTCAGCAGCTAAGAGCACTGGGACGCCCACCG
CCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAATTCTGGAACAC AAGAAGAGAAATTGCTGGGTTTAGAACAAGATTATAAACGAATTCGGTGC TCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAATATTACCCAAAATGCTC CCCAAATAAGAAATGCATCAGCTCAGTCAGTGAATACAAAAAAGGAATTAT TTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTCCAACCCCACCCTCTAT TCTGTTTCTTCCTCCTCACATGGGGGTACACATACACAGCTTCCTCTTTTG GTTCCATCCTTACCACCACACCACACGCACACTCCACATGCCCAGCAGAG TGGCACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCTGCTGTCTGTAGT TCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACCCCCTTCCTTGTG ACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCCACACATTCTCAA CCATAGTCCTTCTAACAATACCAATAGCTAGGACCCGGCTGCTGTGCACT GGGACTGGGGATTCCACATGTTTGCCTTGGGAGTCTCAAGCTGGACTGC CA 77 OPA1- GTGCTGCCCGCCTAGAAAGGGTGAAGTGGTTGTTTCCGTGACGGACTGA ND6- GTACGGGTGCCTGTCAGGCTCTTGCGGAAGTCCATGCGCCATTGGGAGG 3'UTR GCCTCGGCCGCGGCTCTGTGCCCTTGCTGCTGAGGGCCACTTCCTGGGT CATTCCTGGACCGGGAGCCGGGCTGGGGCTCACACGGGGGCTCCCGCG TGGCCGTCTCGGCGCCTGCGTGACCTCCCCGCCGGCGGGATGTGGCGA CTACGTCGGGCCGCTGTGGCCTGATGATGTATGCTTTGTTTCTGTTGAGT GTGGGTTTAGTAATGGGGTTTGTGGGGTTTTCTTCTAAGCCTTCTCCTATT TATGGGGGTTTAGTATTGATTGTTAGCGGTGTGGTCGGGTGTGTTATTATT CTGAATTTTGGGGGAGGTTATATGGGTTTAATGGTTTTTTTAATTTATTTAG GGGGAATGATGGTTGTCTTTGGATATACTACAGCGATGGCTATTGAGGAG TATCCTGAGGCATGGGGGTCAGGGGTTGAGGTCTTGGTGAGTGTTTTAG TGGGGTTAGCGATGGAGGTAGGATTGGTGCTGTGGGTGAAAGAGTATGA TGGGGTGGTGGTTGTGGTAAACTTTAATAGTGTAGGAAGCTGGATGATTT ATGAAGGAGAGGGGTCAGGGTTGATTCGGGAGGATCCTATTGGTGCGGG GGCTTTGTATGATTATGGGCGTTGGTTAGTAGTAGTTACTGGTTGGACATT GTTTGTTGGTGTATATATTGTAATTGAGATTGCTCGGGGGAATTAGGAGC ACTGGGACGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTG TGGTAATTCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAACAAGATT ATAAACGAATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAA TATTACCCAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAA TACAAAAAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTC CAACCCCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTACACATAC ACAGCTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGCACACTC CACATGCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCAT GATCTGCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAG CACCCCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCA CCCCACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCTAGGACC CGGCTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTTGGGAGT CTCAAGCTGGACTGCCAGCCCCTGTCCTCCCTTCACCCCCATTGCGTATG AGCATTTCAGAACTCCAAGGAGTCACAGGCATCTTTATAGTTCACGTTAAC ATATAGACACTGTTGGAAGCAGTTCCTTCTAAAAGGGTAGCCCTGGACTT AATACCAGCCGGATACCTCTGGCCCCCACCCCATTACTGTACCTCTGGAG TCACTACTGTGGGTCGCCACTCCTCTGCTACACAGCACGGCTTTTTCAAG GCTGTATTGAGAAGGGAAGTTAGGAAGAAGGGTGTGCTGGGCTAACCAG CCCACAGAGCTCACATTCCTGTCCCTTGGGTGAAAAATACATGTCCATCC TGATATCTCCTGAATTCAGAAATTAGCCTCCACATGTGCAATGGCTTTAAG AGCCAGAAGCAGGGTTCTGGGAATTTTGCAAGTTACCTGTGGCCAGGTG TGGTCTCGGTTACCAAATACGGTTACCTGCAGCTTTTTAGTCCTTTGTGCT CCCACGGGTCTACAGAGTCCCATCTGCCCAAAGGTCTTGAAGCTTGACA GGATGTTTTCGATTACTCAGTCTCCCAGGGCACTACTGGTCCGTAGGATT CGATTGGTCGGGGTAGGAGAGTTAAACAACATTTAAACAGAGTTCTCTCA AAAATGTCTAAAGGGATTGTAGGTAGATAACATCCAATCACTGTTTGCACT TATCTGAAATCTTCCCTCTTGGCTGCCCCCAGGTATTTACTGTGGAGAAC ATTGCATAGGAATGTCTGGAAAAAGCTTCTACAACTTGTTACAGCCTTCAC ATTTGTAGAAGCTTT 78 OPA1- GTGCTGCCCGCCTAGAAAGGGTGAAGTGGTTGTTTCCGTGACGGACTGA ND6- GTACGGGTGCCTGTCAGGCTCTTGCGGAAGTCCATGCGCCATTGGGAGG 3'UTR* GCCTCGGCCGCGGCTCTGTGCCCTTGCTGCTGAGGGCCACTTCCTGGGT CATTCCTGGACCGGGAGCCGGGCTGGGGCTCACACGGGGGCTCCCGCG TGGCCGTCTCGGCGCCTGCGTGACCTCCCCGCCGGCGGGATGTGGCGA CTACGTCGGGCCGCTGTGGCCTGATGATGTATGCTTTGTTTCTGTTGAGT GTGGGTTTAGTAATGGGGTTTGTGGGGTTTTCTTCTAAGCCTTCTCCTATT TATGGGGGTTTAGTATTGATTGTTAGCGGTGTGGTCGGGTGTGTTATTATT CTGAATTTTGGGGGAGGTTATATGGGTTTAATGGTTTTTTTAATTTATTTAG GGGGAATGATGGTTGTCTTTGGATATACTACAGCGATGGCTATTGAGGAG TATCCTGAGGCATGGGGGTCAGGGGTTGAGGTCTTGGTGAGTGTTTTAG TGGGGTTAGCGATGGAGGTAGGATTGGTGCTGTGGGTGAAAGAGTATGA TGGGGTGGTGGTTGTGGTAAACTTTAATAGTGTAGGAAGCTGGATGATTT ATGAAGGAGAGGGGTCAGGGTTGATTCGGGAGGATCCTATTGGTGCGGG GGCTTTGTATGATTATGGGCGTTGGTTAGTAGTAGTTACTGGTTGGACATT GTTTGTTGGTGTATATATTGTAATTGAGATTGCTCGGGGGAATTAGGAGC ACTGGGACGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGCATGTTG TGGTAATTCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAACAAGATT ATAAACGAATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTTTTTAAA TATTACCCAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGTCAGTGAA TACAAAAAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATCTCTCCTC CAACCCCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTACACATAC ACAGCTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGCACACTC CACATGCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCCTCAT GATCTGCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCGGAG CACCCCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTCCCCA CCCCACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCTAGGACC CGGCTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTTGGGAGT CTCAAGCTGGACTGCCA 79 OPA1- GTGCTGCCCGCCTAGAAAGGGTGAAGTGGTTGTTTCCGTGACGGACTGA opt_ND6- GTACGGGTGCCTGTCAGGCTCTTGCGGAAGTCCATGCGCCATTGGGAGG 3'UTR GCCTCGGCCGCGGCTCTGTGCCCTTGCTGCTGAGGGCCACTTCCTGGGT CATTCCTGGACCGGGAGCCGGGCTGGGGCTCACACGGGGGCTCCCGCG TGGCCGTCTCGGCGCCTGCGTGACCTCCCCGCCGGCGGGATGTGGCGA CTACGTCGGGCCGCTGTGGCCTGATGATGTACGCCCTGTTCCTGCTGAG CGTGGGCCTGGTGATGGGCTTCGTGGGCTTCAGCAGCAAGCCCAGCCC CATCTACGGCGGCCTGGTGCTGATCGTGAGCGGCGTGGTGGGCTGCGT GATCATCCTGAACTTCGGCGGCGGCTACATGGGCCTGATGGTGTTCCTG ATCTACCTGGGCGGCATGATGGTGGTGTTCGGCTACACCACCGCCATGG CCATCGAGGAGTACCCCGAGGCCTGGGGCAGCGGCGTGGAGGTGCTGG TGAGCGTGCTGGTGGGCCTGGCCATGGAGGTGGGCCTGGTGCTGTGGG TGAAGGAGTACGACGGCGTGGTGGTGGTGGTGAACTTCAACAGCGTGGG CAGCTGGATGATCTACGAGGGCGAGGGCAGCGGCCTGATCCGCGAGGA CCCCATCGGCGCCGGCGCCCTGTACGACTACGGCCGCTGGCTGGTGGT GGTGACCGGCTGGACCCTGTTCGTGGGCGTGTACATCGTGATCGAGATC GCCCGCGGCAACTAAGAGCACTGGGACGCCCACCGCCCCTTTCCCTCCG CTGCCAGGCGAGCATGTTGTGGTAATTCTGGAACACAAGAAGAGAAATTG CTGGGTTTAGAACAAGATTATAAACGAATTCGGTGCTCAGTGATCACTTGA CAGTTTTTTTTTTTTTTAAATATTACCCAAAATGCTCCCCAAATAAGAAATG CATCAGCTCAGTCAGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGG TCTTTTATACATCTCTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCT CACATGGGGGTACACATACACAGCTTCCTCTTTTGGTTCCATCCTTACCA CCACACCACACGCACACTCCACATGCCCAGCAGAGTGGCACTTGGTGGC CAGAAAGTGTGAGCCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGG TCCCTCAAAGGCCTCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCC TGCATTTTTGGTTTTCCCCACCCCACACATTCTCAACCATAGTCCTTCTAA CAATACCAATAGCTAGGACCCGGCTGCTGTGCACTGGGACTGGGGATTC CACATGTTTGCCTTGGGAGTCTCAAGCTGGACTGCCAGCCCCTGTCCTCC CTTCACCCCCATTGCGTATGAGCATTTCAGAACTCCAAGGAGTCACAGGC ATCTTTATAGTTCACGTTAACATATAGACACTGTTGGAAGCAGTTCCTTCT AAAAGGGTAGCCCTGGACTTAATACCAGCCGGATACCTCTGGCCCCCAC CCCATTACTGTACCTCTGGAGTCACTACTGTGGGTCGCCACTCCTCTGCT ACACAGCACGGCTTTTTCAAGGCTGTATTGAGAAGGGAAGTTAGGAAGAA GGGTGTGCTGGGCTAACCAGCCCACAGAGCTCACATTCCTGTCCCTTGG GTGAAAAATACATGTCCATCCTGATATCTCCTGAATTCAGAAATTAGCCTC CACATGTGCAATGGCTTTAAGAGCCAGAAGCAGGGTTCTGGGAATTTTGC AAGTTACCTGTGGCCAGGTGTGGTCTCGGTTACCAAATACGGTTACCTGC AGCTTTTTAGTCCTTTGTGCTCCCACGGGTCTACAGAGTCCCATCTGCCC AAAGGTCTTGAAGCTTGACAGGATGTTTTCGATTACTCAGTCTCCCAGGG CACTACTGGTCCGTAGGATTCGATTGGTCGGGGTAGGAGAGTTAAACAAC ATTTAAACAGAGTTCTCTCAAAAATGTCTAAAGGGATTGTAGGTAGATAAC ATCCAATCACTGTTTGCACTTATCTGAAATCTTCCCTCTTGGCTGCCCCCA GGTATTTACTGTGGAGAACATTGCATAGGAATGTCTGGAAAAAGCTTCTA CAACTTGTTACAGCCTTCACATTTGTAGAAGCTTT 80 OPA1- GTGCTGCCCGCCTAGAAAGGGTGAAGTGGTTGTTTCCGTGACGGACTGA opt_ND6- GTACGGGTGCCTGTCAGGCTCTTGCGGAAGTCCATGCGCCATTGGGAGG 3'UTR* GCCTCGGCCGCGGCTCTGTGCCCTTGCTGCTGAGGGCCACTTCCTGGGT CATTCCTGGACCGGGAGCCGGGCTGGGGCTCACACGGGGGCTCCCGCG TGGCCGTCTCGGCGCCTGCGTGACCTCCCCGCCGGCGGGATGTGGCGA CTACGTCGGGCCGCTGTGGCCTGATGATGTACGCCCTGTTCCTGCTGAG CGTGGGCCTGGTGATGGGCTTCGTGGGCTTCAGCAGCAAGCCCAGCCC CATCTACGGCGGCCTGGTGCTGATCGTGAGCGGCGTGGTGGGCTGCGT GATCATCCTGAACTTCGGCGGCGGCTACATGGGCCTGATGGTGTTCCTG ATCTACCTGGGCGGCATGATGGTGGTGTTCGGCTACACCACCGCCATGG CCATCGAGGAGTACCCCGAGGCCTGGGGCAGCGGCGTGGAGGTGCTGG TGAGCGTGCTGGTGGGCCTGGCCATGGAGGTGGGCCTGGTGCTGTGGG TGAAGGAGTACGACGGCGTGGTGGTGGTGGTGAACTTCAACAGCGTGGG CAGCTGGATGATCTACGAGGGCGAGGGCAGCGGCCTGATCCGCGAGGA CCCCATCGGCGCCGGCGCCCTGTACGACTACGGCCGCTGGCTGGTGGT GGTGACCGGCTGGACCCTGTTCGTGGGCGTGTACATCGTGATCGAGATC GCCCGCGGCAACTAAGAGCACTGGGACGCCCACCGCCCCTTTCCCTCCG CTGCCAGGCGAGCATGTTGTGGTAATTCTGGAACACAAGAAGAGAAATTG CTGGGTTTAGAACAAGATTATAAACGAATTCGGTGCTCAGTGATCACTTGA CAGTTTTTTTTTTTTTTAAATATTACCCAAAATGCTCCCCAAATAAGAAATG CATCAGCTCAGTCAGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGG TCTTTTATACATCTCTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCT CACATGGGGGTACACATACACAGCTTCCTCTTTTGGTTCCATCCTTACCA CCACACCACACGCACACTCCACATGCCCAGCAGAGTGGCACTTGGTGGC CAGAAAGTGTGAGCCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGG TCCCTCAAAGGCCTCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCC TGCATTTTTGGTTTTCCCCACCCCACACATTCTCAACCATAGTCCTTCTAA CAATACCAATAGCTAGGACCCGGCTGCTGTGCACTGGGACTGGGGATTC CACATGTTTGCCTTGGGAGTCTCAAGCTGGACTGCCA 81 OPA1- GTGCTGCCCGCCTAGAAAGGGTGAAGTGGTTGTTTCCGTGACGGACTGA ND1- GTACGGGTGCCTGTCAGGCTCTTGCGGAAGTCCATGCGCCATTGGGAGG 3'UTR GCCTCGGCCGCGGCTCTGTGCCCTTGCTGCTGAGGGCCACTTCCTGGGT CATTCCTGGACCGGGAGCCGGGCTGGGGCTCACACGGGGGCTCCCGCG TGGCCGTCTCGGCGCCTGCGTGACCTCCCCGCCGGCGGGATGTGGCGA CTACGTCGGGCCGCTGTGGCCTGATGCCCATGGCCAACCTCCTACTCCT CATTGTACCCATTCTAATCGCAATGGCATTCCTAATGCTTACCGAACGAAA AATTCTAGGCTATATGCAACTACGCAAAGGCCCCAACGTTGTAGGCCCCT ACGGGCTACTACAACCCTTCGCTGACGCCATGAAACTCTTCACCAAAGAG CCCCTAAAACCCGCCACATCTACCATCACCCTCTACATCACCGCCCCGAC CTTAGCTCTCACCATCGCTCTTCTACTATGGACCCCCCTCCCCATGCCCA ACCCCCTGGTCAACCTCAACCTAGGCCTCCTATTTATTCTAGCCACCTCTA GCCTAGCCGTTTACTCAATCCTCTGGTCAGGGTGGGCATCAAACTCAAAC TACGCCCTGATCGGCGCACTGCGAGCAGTAGCCCAAACAATCTCATATGA AGTCACCCTAGCCATCATTCTACTATCAACATTACTAATGAGTGGCTCCTT TAACCTCTCCACCCTTATCACAACACAAGAACACCTCTGGTTACTCCTGCC ATCATGGCCCTTGGCCATGATGTGGTTTATCTCCACACTAGCAGAGACCA ACCGAACCCCCTTCGACCTTGCCGAAGGGGAGTCCGAACTAGTCTCAGG CTTCAACATCGAATACGCCGCAGGCCCCTTCGCCCTATTCTTCATGGCCG AATACACAAACATTATTATGATGAACACCCTCACCACTACAATCTTCCTAG GAACAACATATGACGCACTCTCCCCTGAACTCTACACAACATATTTTGTCA CCAAGACCCTACTTCTAACCTCCCTGTTCTTATGGATTCGAACAGCATACC CCCGATTCCGCTACGACCAACTCATGCACCTCCTATGGAAAAACTTCCTA CCACTCACCCTAGCATTACTTATGTGGTATGTCTCCATGCCCATTACAATC TCCAGCATTCCCCCTCAAACCTAAGAGCACTGGGACGCCCACCGCCCCT TTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAATTCTGGAACACAAGAA GAGAAATTGCTGGGTTTAGAACAAGATTATAAACGAATTCGGTGCTCAGT GATCACTTGACAGTTTTTTTTTTTTTTAAATATTACCCAAAATGCTCCCCAA ATAAGAAATGCATCAGCTCAGTCAGTGAATACAAAAAAGGAATTATTTTTC CCTTTGAGGGTCTTTTATACATCTCTCCTCCAACCCCACCCTCTATTCTGT TTCTTCCTCCTCACATGGGGGTACACATACACAGCTTCCTCTTTTGGTTCC ATCCTTACCACCACACCACACGCACACTCCACATGCCCAGCAGAGTGGC ACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCTGCTGTCTGTAGTTCTG TGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACCCCCTTCCTTGTGACTG AGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCCACACATTCTCAACCAT AGTCCTTCTAACAATACCAATAGCTAGGACCCGGCTGCTGTGCACTGGGA CTGGGGATTCCACATGTTTGCCTTGGGAGTCTCAAGCTGGACTGCCAGC CCCTGTCCTCCCTTCACCCCCATTGCGTATGAGCATTTCAGAACTCCAAG GAGTCACAGGCATCTTTATAGTTCACGTTAACATATAGACACTGTTGGAAG CAGTTCCTTCTAAAAGGGTAGCCCTGGACTTAATACCAGCCGGATACCTC TGGCCCCCACCCCATTACTGTACCTCTGGAGTCACTACTGTGGGTCGCCA CTCCTCTGCTACACAGCACGGCTTTTTCAAGGCTGTATTGAGAAGGGAAG TTAGGAAGAAGGGTGTGCTGGGCTAACCAGCCCACAGAGCTCACATTCC TGTCCCTTGGGTGAAAAATACATGTCCATCCTGATATCTCCTGAATTCAGA AATTAGCCTCCACATGTGCAATGGCTTTAAGAGCCAGAAGCAGGGTTCTG GGAATTTTGCAAGTTACCTGTGGCCAGGTGTGGTCTCGGTTACCAAATAC GGTTACCTGCAGCTTTTTAGTCCTTTGTGCTCCCACGGGTCTACAGAGTC CCATCTGCCCAAAGGTCTTGAAGCTTGACAGGATGTTTTCGATTACTCAG TCTCCCAGGGCACTACTGGTCCGTAGGATTCGATTGGTCGGGGTAGGAG AGTTAAACAACATTTAAACAGAGTTCTCTCAAAAATGTCTAAAGGGATTGT AGGTAGATAACATCCAATCACTGTTTGCACTTATCTGAAATCTTCCCTCTT GGCTGCCCCCAGGTATTTACTGTGGAGAACATTGCATAGGAATGTCTGGA AAAAGCTTCTACAACTTGTTACAGCCTTCACATTTGTAGAAGCTTT 82 OPA1- GTGCTGCCCGCCTAGAAAGGGTGAAGTGGTTGTTTCCGTGACGGACTGA ND1- GTACGGGTGCCTGTCAGGCTCTTGCGGAAGTCCATGCGCCATTGGGAGG 3'UTR* GCCTCGGCCGCGGCTCTGTGCCCTTGCTGCTGAGGGCCACTTCCTGGGT CATTCCTGGACCGGGAGCCGGGCTGGGGCTCACACGGGGGCTCCCGCG TGGCCGTCTCGGCGCCTGCGTGACCTCCCCGCCGGCGGGATGTGGCGA CTACGTCGGGCCGCTGTGGCCTGATGCCCATGGCCAACCTCCTACTCCT CATTGTACCCATTCTAATCGCAATGGCATTCCTAATGCTTACCGAACGAAA AATTCTAGGCTATATGCAACTACGCAAAGGCCCCAACGTTGTAGGCCCCT ACGGGCTACTACAACCCTTCGCTGACGCCATGAAACTCTTCACCAAAGAG CCCCTAAAACCCGCCACATCTACCATCACCCTCTACATCACCGCCCCGAC CTTAGCTCTCACCATCGCTCTTCTACTATGGACCCCCCTCCCCATGCCCA ACCCCCTGGTCAACCTCAACCTAGGCCTCCTATTTATTCTAGCCACCTCTA GCCTAGCCGTTTACTCAATCCTCTGGTCAGGGTGGGCATCAAACTCAAAC TACGCCCTGATCGGCGCACTGCGAGCAGTAGCCCAAACAATCTCATATGA AGTCACCCTAGCCATCATTCTACTATCAACATTACTAATGAGTGGCTCCTT TAACCTCTCCACCCTTATCACAACACAAGAACACCTCTGGTTACTCCTGCC ATCATGGCCCTTGGCCATGATGTGGTTTATCTCCACACTAGCAGAGACCA ACCGAACCCCCTTCGACCTTGCCGAAGGGGAGTCCGAACTAGTCTCAGG CTTCAACATCGAATACGCCGCAGGCCCCTTCGCCCTATTCTTCATGGCCG AATACACAAACATTATTATGATGAACACCCTCACCACTACAATCTTCCTAG GAACAACATATGACGCACTCTCCCCTGAACTCTACACAACATATTTTGTCA CCAAGACCCTACTTCTAACCTCCCTGTTCTTATGGATTCGAACAGCATACC CCCGATTCCGCTACGACCAACTCATGCACCTCCTATGGAAAAACTTCCTA CCACTCACCCTAGCATTACTTATGTGGTATGTCTCCATGCCCATTACAATC TCCAGCATTCCCCCTCAAACCTAAGAGCACTGGGACGCCCACCGCCCCT TTCCCTCCGCTGCCAGGCGAGCATGTTGTGGTAATTCTGGAACACAAGAA GAGAAATTGCTGGGTTTAGAACAAGATTATAAACGAATTCGGTGCTCAGT GATCACTTGACAGTTTTTTTTTTTTTTAAATATTACCCAAAATGCTCCCCAA ATAAGAAATGCATCAGCTCAGTCAGTGAATACAAAAAAGGAATTATTTTTC CCTTTGAGGGTCTTTTATACATCTCTCCTCCAACCCCACCCTCTATTCTGT TTCTTCCTCCTCACATGGGGGTACACATACACAGCTTCCTCTTTTGGTTCC
ATCCTTACCACCACACCACACGCACACTCCACATGCCCAGCAGAGTGGC ACTTGGTGGCCAGAAAGTGTGAGCCTCATGATCTGCTGTCTGTAGTTCTG TGAGCTCAGGTCCCTCAAAGGCCTCGGAGCACCCCCTTCCTTGTGACTG AGCCAGGGCCTGCATTTTTGGTTTTCCCCACCCCACACATTCTCAACCAT AGTCCTTCTAACAATACCAATAGCTAGGACCCGGCTGCTGTGCACTGGGA CTGGGGATTCCACATGTTTGCCTTGGGAGTCTCAAGCTGGACTGCCA 83 OPA1- GTGCTGCCCGCCTAGAAAGGGTGAAGTGGTTGTTTCCGTGACGGACTGA opt_ND1- GTACGGGTGCCTGTCAGGCTCTTGCGGAAGTCCATGCGCCATTGGGAGG 3'UTR GCCTCGGCCGCGGCTCTGTGCCCTTGCTGCTGAGGGCCACTTCCTGGGT CATTCCTGGACCGGGAGCCGGGCTGGGGCTCACACGGGGGCTCCCGCG TGGCCGTCTCGGCGCCTGCGTGACCTCCCCGCCGGCGGGATGTGGCGA CTACGTCGGGCCGCTGTGGCCTGATGCCCATGGCCAACCTGCTGCTGCT GATCGTGCCCATCCTGATCGCCATGGCCTTCCTGATGCTGACCGAGCGC AAGATCCTGGGCTACATGCAGCTGCGCAAGGGCCCCAACGTGGTGGGC CCCTACGGCCTGCTGCAGCCCTTCGCCGACGCCATGAAGCTGTTCACCA AGGAGCCCCTGAAGCCCGCCACCAGCACCATCACCCTGTACATCACCGC CCCCACCCTGGCCCTGACCATCGCCCTGCTGCTGTGGACCCCCCTGCCC ATGCCCAACCCCCTGGTGAACCTGAACCTGGGCCTGCTGTTCATCCTGG CCACCAGCAGCCTGGCCGTGTACAGCATCCTGTGGAGCGGCTGGGCCA GCAACAGCAACTACGCCCTGATCGGCGCCCTGCGCGCCGTGGCCCAGA CCATCAGCTACGAGGTGACCCTGGCCATCATCCTGCTGAGCACCCTGCT GATGAGCGGCAGCTTCAACCTGAGCACCCTGATCACCACCCAGGAGCAC CTGTGGCTGCTGCTGCCCAGCTGGCCCCTGGCCATGATGTGGTTCATCA GCACCCTGGCCGAGACCAACCGCACCCCCTTCGACCTGGCCGAGGGCG AGAGCGAGCTGGTGAGCGGCTTCAACATCGAGTACGCCGCCGGCCCCTT CGCCCTGTTCTTCATGGCCGAGTACACCAACATCATCATGATGAACACCC TGACCACCACCATCTTCCTGGGCACCACCTACGACGCCCTGAGCCCCGA GCTGTACACCACCTACTTCGTGACCAAGACCCTGCTGCTGACCAGCCTGT TCCTGTGGATCCGCACCGCCTACCCCCGCTTCCGCTACGACCAGCTGAT GCACCTGCTGTGGAAGAACTTCCTGCCCCTGACCCTGGCCCTGCTGATG TGGTACGTGAGCATGCCCATCACCATCAGCAGCATCCCCCCCCAGACCT AAGAGCACTGGGACGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAG CATGTTGTGGTAATTCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAA CAAGATTATAAACGAATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTT TTTTAAATATTACCCAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGT CAGTGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATC TCTCCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTA CACATACACAGCTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGC ACACTCCACATGCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAG CCTCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCC TCGGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTT TCCCCACCCCACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCT AGGACCCGGCTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTT GGGAGTCTCAAGCTGGACTGCCAGCCCCTGTCCTCCCTTCACCCCCATT GCGTATGAGCATTTCAGAACTCCAAGGAGTCACAGGCATCTTTATAGTTC ACGTTAACATATAGACACTGTTGGAAGCAGTTCCTTCTAAAAGGGTAGCC CTGGACTTAATACCAGCCGGATACCTCTGGCCCCCACCCCATTACTGTAC CTCTGGAGTCACTACTGTGGGTCGCCACTCCTCTGCTACACAGCACGGC TTTTTCAAGGCTGTATTGAGAAGGGAAGTTAGGAAGAAGGGTGTGCTGGG CTAACCAGCCCACAGAGCTCACATTCCTGTCCCTTGGGTGAAAAATACAT GTCCATCCTGATATCTCCTGAATTCAGAAATTAGCCTCCACATGTGCAATG GCTTTAAGAGCCAGAAGCAGGGTTCTGGGAATTTTGCAAGTTACCTGTGG CCAGGTGTGGTCTCGGTTACCAAATACGGTTACCTGCAGCTTTTTAGTCC TTTGTGCTCCCACGGGTCTACAGAGTCCCATCTGCCCAAAGGTCTTGAAG CTTGACAGGATGTTTTCGATTACTCAGTCTCCCAGGGCACTACTGGTCCG TAGGATTCGATTGGTCGGGGTAGGAGAGTTAAACAACATTTAAACAGAGT TCTCTCAAAAATGTCTAAAGGGATTGTAGGTAGATAACATCCAATCACTGT TTGCACTTATCTGAAATCTTCCCTCTTGGCTGCCCCCAGGTATTTACTGTG GAGAACATTGCATAGGAATGTCTGGAAAAAGCTTCTACAACTTGTTACAG CCTTCACATTTGTAGAAGCTTT 84 OPA1- GTGCTGCCCGCCTAGAAAGGGTGAAGTGGTTGTTTCCGTGACGGACTGA opt_ND1- GTACGGGTGCCTGTCAGGCTCTTGCGGAAGTCCATGCGCCATTGGGAGG 3'UTR* GCCTCGGCCGCGGCTCTGTGCCCTTGCTGCTGAGGGCCACTTCCTGGGT CATTCCTGGACCGGGAGCCGGGCTGGGGCTCACACGGGGGCTCCCGCG TGGCCGTCTCGGCGCCTGCGTGACCTCCCCGCCGGCGGGATGTGGCGA CTACGTCGGGCCGCTGTGGCCTGATGCCCATGGCCAACCTGCTGCTGCT GATCGTGCCCATCCTGATCGCCATGGCCTTCCTGATGCTGACCGAGCGC AAGATCCTGGGCTACATGCAGCTGCGCAAGGGCCCCAACGTGGTGGGC CCCTACGGCCTGCTGCAGCCCTTCGCCGACGCCATGAAGCTGTTCACCA AGGAGCCCCTGAAGCCCGCCACCAGCACCATCACCCTGTACATCACCGC CCCCACCCTGGCCCTGACCATCGCCCTGCTGCTGTGGACCCCCCTGCCC ATGCCCAACCCCCTGGTGAACCTGAACCTGGGCCTGCTGTTCATCCTGG CCACCAGCAGCCTGGCCGTGTACAGCATCCTGTGGAGCGGCTGGGCCA GCAACAGCAACTACGCCCTGATCGGCGCCCTGCGCGCCGTGGCCCAGA CCATCAGCTACGAGGTGACCCTGGCCATCATCCTGCTGAGCACCCTGCT GATGAGCGGCAGCTTCAACCTGAGCACCCTGATCACCACCCAGGAGCAC CTGTGGCTGCTGCTGCCCAGCTGGCCCCTGGCCATGATGTGGTTCATCA GCACCCTGGCCGAGACCAACCGCACCCCCTTCGACCTGGCCGAGGGCG AGAGCGAGCTGGTGAGCGGCTTCAACATCGAGTACGCCGCCGGCCCCTT CGCCCTGTTCTTCATGGCCGAGTACACCAACATCATCATGATGAACACCC TGACCACCACCATCTTCCTGGGCACCACCTACGACGCCCTGAGCCCCGA GCTGTACACCACCTACTTCGTGACCAAGACCCTGCTGCTGACCAGCCTGT TCCTGTGGATCCGCACCGCCTACCCCCGCTTCCGCTACGACCAGCTGAT GCACCTGCTGTGGAAGAACTTCCTGCCCCTGACCCTGGCCCTGCTGATG TGGTACGTGAGCATGCCCATCACCATCAGCAGCATCCCCCCCCAGACCT AA GAGCACTGGGACGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGCAT GTTGTGGTAATTCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAACAA GATTATAAACGAATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTTTT TAAATATTACCCAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGTCAG TGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGGTCTTTTATACATCTCT CCTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTACA CATACACAGCTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGCAC ACTCCACATGCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCC TCATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTC GGAGCACCCCCTTCCTTGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTC CCCACCCCACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCTAG GACCCGGCTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTTGG GAGTCTCAAGCTGGACTGCCA 85 .beta.-actin-S CGAGATCGTGCGGGACAT primer 86 .beta.-actin-A CAGGAAGGAGGGCTGGAAC primer 87 ND4-S CTGCCTACGACAAACAGAC primer 88 ND4-A AGTGCGTTCGTAGTTTGAG primer 89 ND6-F ATGATGTATGCTTTGTTTCTG primer 90 ND6-R CTAATTCCCCCGAGCAATCTC primer 91 ND6-S AGTGTGGGTTTAGTAATG primer 92 ND6-A TGCCTCAGGATACTCCTC primer 93 .beta.-actin-F CTCCATCCTGGCCTCGCTGT primer 94 .beta.-actin-R GCTGTCACCTTCACCGTTCC primer 95 ND6-F GGGTTTTCTTCTAAGCCTTCTCC primer 96 ND6-R CCATCATACTCTTTCACCCACAG primer 97 opt_ND6- CGCCTGCTGACCGGCTGCGT F primer 98 opt_ND6- CCAGGCCTCGGGGTACTCCT R 99 ND1-F ATGGCCGCATCTCCGCACACT primer 100 ND1-R TTAGGTTTGAGGGGGAATGCT primer 101 ND1-F AACCTCAACCTAGGCCTCCTA primer 102 ND1-R TGGCAGGAGTAACCAGAGGTG primer 103 N1-F AGGAGGCTCTGTCTGGTATCTTG primer 104 ND1-R TTTTAGGGGCTCTTTGGTGAA primer 105 opt-ND1-F GCCGCCTGCTGACCGGCTGCGT primer 106 opt-ND1-R TGATGTACAGGGTGATGGTGCTGG primer 107 ND4-S GCCAACAGCAACTACGAGC primer 108 ND4-A TGATGTTGCTCCAGCTGAAG primer 109 opt-ND4-S GCCTGACCCTGATCCTGAAC primer 110 opt-ND4-A GTGCGCTCGTAGTTGCTGTT primer 111 hsACO2 GGGCAGTGCCTCCCCGCCCCGCCGCTGGCGTCAAGTTCAGCTCCACGT GTGCCATCAGTGGATCCGATCCGTCCAGCCATGGCTTCCTATTCCAAGAT GGTGTGACCAGACATGCTTCCTGCTCCCCGCTTAGCCCACGGAGTGACT GTGGTTGTGGTGGGGGGGTTCTTAAAATAACTTTTTAGCCCCCGTCTTCC TATTTTGAGTTTGGTTCAGATCTTAAGCAGCTCCATGCAACTGTATTTATTT TTGATGACAAGACTCCCATCTAAAGTTTTTCTCCTGCCTGATCATTTCATT GGTGGCTGAAGGATTCTAGAGAACCTTTTGTTCTTGCAAGGAAAACAAGA ATCCAAAACCAGTGACTGTTCTGTGA 112 hsATP5B GGGGTCTTTGTCCTCTGTACTGTCTCTCTCCTTGCCCCTAACCCAAAAAG CTTCATTTTTCTGTGTAGGCTGCACAAGAGCCTTGATTGAAGATATATTCT TTCTGAACAGTATTTAAGGTTTCCAATAAAATGTACACCCCTCAG 113 hsAK2 TGTTGGGTCCAAGAAGGAATTTCTTTCCATCCCTGTGAGGCAATGGGTGG GAATGATAGGACAGGCAAAGAGAAGCTTCCTCAGGCTAGCAAAAATATCA TTTGATGTATTGATTAAAAAAGCACTTGCTTGATGTATCTTTGGCGTGTGT GCTACTCTCATCTGTGTGTATGTGTGTTGTGTGTGTGTGTGTGTGCATGC ACATATGTGTTCACTCTGCTACTTTGTAAGTTTTAGGCTAGGTTGCTTTAC CAGCTGTTTACTTCTTTTTTGTTGTTGTTTTGAGACAAGGTTTCGCTCTGC CACCCTGGCTGGAGTGCAGTGGCGTGATCTTGGCTCACGGCAACCTCTG CCTCCTGGGGCTCAAGCAATTATCCCACCTCAGCCTCCTGAGCAGCTGG GACTACAGGTGCATGCCACAACACCTGGCTGATATTTGTATTTTTTGTAGA GACAGGATTTTGCCAAGTTGCCCAGGCTGGTCTTGAACTCCTAGGCTTAA GCAATCCACCCACCTTGGCCTCCTGAAGTGCCAGGATCACAGACGTGAG CCACTACACCCAGCCCAGCTGTTTACTTCTTTAACCATACTTTTGATTTTAT TTTTTGACCAAAATGAACTAACCCAGGTAATCTTCCAGGGACCGCAATTCC AGAACCTCATAGTATTTCTTCCATTTCCAGCAGCTGATTAGAAGTCCAGGA TCATGTGAAGTCAGGCAGGGTCACAGTTCCTGATGGCACATTATGGACAG AGAATTCCATTTTGTTTTCTAACCCATGATGAAAACCCACGTGAGTCAGTG TGTGAACAGGGATCATTAATTTTTTCCCCCTAGGTGGAAGGAAAAAGGCA CTTACTTTGCAGGTTACAGAAATTACTGGGAGAGGATATCGTCATAAAAAG AGCCAGGCCAAATTGGAATATTTTTGTGATCTGCATCATGATGCTGAAAAT AGCAATTATTTGGGAATTGGGTTTGAAAACTGAATTGTTGCCAGAGAATTA AACCAGGTGAAAGGTCCTTTTGAATTCAGATTGTCTTCTGAACATCCAGG CTGATCATCTGAGAGCAGTCAAATCTACTTCCCCAAAAAGAGACCAGGGT AGGTTTATTTGCTTTTATTTTTAATGTTTGCCTGTGTTTCCAAGTGTGAACA AAACAGTGTGTGATCTATTCTTGGATTCATTTTGATCAGTATTTATTCAAAC CCAGTCTCTCTCCAGGACATAAAACTGAAATCAGATATGTTCTTTTTAAGC CCAAACCCTCTCCTTTCTAGATCCAACCCTTCACCCCTAATTTTATGATGG CTATAGCCATGGACTTCCCCAAGAAAAGATCACCCAGAAATAAGACCACC TGTGACAGTTACCAGCTTTTATTCATAACCTTAGCTTCCCAACTATTGAGC ATTTTCTAAGGTCCCTGCTGTCTTTTGGTCTCTGGTTTGATTTGTGGCAAA CAGATGAAGTAACAGACTGCTATGAAGGACCACAAAAACGGCAGCCTCT GGAAAAACCATTAGAAAGTCAGTGGCAGATCCAGTAAATAATATCGCCAG CCTCAGCATAATCTGCTGCTGACTCGATTCAGTGGACTCTAAAGTGCCCA GCCTCCTGACCTGAGCTCTCCTGCCATCTGTGAGACTACCAGAGGTCTTA TCTGCTGTCCACATGGCAACTGGGCATGAGTACCTGGCCACCTTGCTTCC CTCTTTGCCTGGTCCAAGTGAGTGTCTGCTGCCTCTGTCCTGCCTTGTTT TCCTGGCTCTAAACCAACTCCACCCACTCTTAATGGAAACTCAGTCTGGC TTTGTGTGTTTCTGGGAAGCACATGACTTCTGGGAATGGGCAAGGAAGAG GAGTGAAACAAAAACTGTCAGCTATGTGTGCCTGGTCTGGGATCCTTCTC TGGGTGACAGTGGCATCATGAATCTTAGAATCAGCTCCCC 114 hsALDH2 GAATCATGCAAGCTTCCTCCCTCAGCCATTGATGGAAAGTTCAGCAAGAT CAGCAACAAAACCAAGAAAAATGATCCTTGCGTGCTGAATATCTGAAAAG AGAAATTTTTCCTACAAAATCTCTTGGGTCAAGAAAGTTCTAGAATTTGAAT TGATAAACATGGTGGGTTGGCTGAGGGTAAGAGTATATGAGGAACCTTTT AAACGACAACAATACTGCTAGCTTTCAGGATGATTTTTAAAAAATAGATTC AAATGTGTTATCCTCTCTCTGAAACGCTTCCTATAACTCGAGTTTATAGGG GAAGAAAAAGCTATTGTTTACAATTATATCACCATTAAGGCAACTGCTACA CCCTGCTTTGTATTCTGGGCTAAGATTCATTAAAAACTAGCTGCTCTTAAC TTACA 115 hsCOX10 GAGCACTGGGACGCCCACCGCCCCTTTCCCTCCGCTGCCAGGCGAGCAT GTTGTGGTAATTCTGGAACACAAGAAGAGAAATTGCTGGGTTTAGAACAA GATTATAAACGAATTCGGTGCTCAGTGATCACTTGACAGTTTTTTTTTTTTT TAAATATTACCCAAAATGCTCCCCAAATAAGAAATGCATCAGCTCAGTCAG TGAATACAAAAAAGGAATTATTTTTCCCTTTGAGGGTCTTTATACATCTCTC CTCCAACCCCACCCTCTATTCTGTTTCTTCCTCCTCACATGGGGGTACAC ATACACAGCTTCCTCTTTTGGTTCCATCCTTACCACCACACCACACGCACA CTCCACATGCCCAGCAGAGTGGCACTTGGTGGCCAGAAAGTGTGAGCCT
CATGATCTGCTGTCTGTAGTTCTGTGAGCTCAGGTCCCTCAAAGGCCTCG GAGCACCCCCTTCCTGGTGACTGAGCCAGGGCCTGCATTTTTGGTTTTCC CCACCCCACACATTCTCAACCATAGTCCTTCTAACAATACCAATAGCTAGG ACCCGGCTGCTGTGCACTGGGACTGGGGATTCCACATGTTTGCCTTGGG AGTCTCAAGCTGGACTGCCAGCCCCTGTCCTCCCTTCACCCCCATTGCGT ATGAGCATTTCAGAACTCCAAGGAGTCACAGGCATCTTTATAGTTCACGTT AACATATAGACACTGTTGGAAGCAGTTCCTTCTAAAAGGGTAGCCCTGGA CTTAATACCAGCCGGATACCTCTGGCCCCCACCCCATTACTGTACCTCTG GAGTCACTACTGTGGGTCGCCACTCCTCTGCTACACAGCACGGCTTTTTC AAGGCTGTATTGAGAAGGGAAGTTAGGAAGAAGGGTGTGCTGGGCTAAC CAGCCCACAGAGCTCACATTCCTGTCCCTTGGGTGAAAAATACATGTCCA TCCTGATATCTCCTGAATTCAGAAATTAGCCTCCACATGTGCAATGGCTTT AAGAGCCAGAAGCAGGGTTCTGGGAATTTTGCAAGTTATCCTGTGGCCAG GTGTGGTCTCGGTTACCAAATACGGTTACCTGCAGCTTTTTAGTCCTTTGT GCTCCCACGGGTCTGCAGAGTCCCATCTGCCCAAAGGTCTTGAAGCTTG ACAGGATGTTTTCATTACTCAGTCTCCCAGGGCACTGCTGGTCCGTAGGG ATTCATTGGTCGGGGTGGGAGAGTTAAACAACATTTAAACAGAGTTCTCT CAAAAATGTCTAAAGGGATTGTAGGTAGATAACATCCAATCACTGTTTGCA CTTATCTGAAATCTTCCCTCTTGGCTGCCCCCAGGTATTTACTGTGGAGAA CATTGCATAGGAATGTCTGGAAAAAGCCTCTACAACTTGTTACAGCCTTCA CATTTGTACAATTCATTGATTCTCTTTTCCTTCCACAATAAAATGGTATACA AGAAC 116 hsUQCRF GAGACTTGGACTCAAGTCATAGGCTTCTTTCAGTCTTTATGTCACCTCAGG S1 AGACTTATTTGAGAGGAAGCCTTCTGTACTTGAAGTTGATTTGAAATATGT AAGAATTGATGATGTATTTGCAAACATTAATGTGAAATAAATTGAATTTAAT GTTGAATACTTTCAGGCATTCACTTAATAAAGACACTGTTAAGCACTGTTA TGCTCAGTCATACACGCGAAAGGTACAATGTCTTTTAGCTAATTCTAATTA AAAATTACAGACTGGTGTACAAGATACTTGTG 117 hsNDUFV CCCACCACCCTGGCCTGCTGTCCTGCGTCTATCCATGTGGAATGCTGGA 1 CAATAAAGCGAGTGCTGCCCACCCTCCAGCTGCC 118 hsNDUFV TTTATATTGAACTGTAAATATGTCACTAGAGAAATAAAATATGGACTTCCAA 2 TCTACGTAAACTTA 119 hsSOD2 ACCACGATCGTTATGCTGAGTATGTTAAGCTCTTTATGACTGTTTTTGTAG TGGTATAGAGTACTGCAGAATACAGTAAGCTGCTCTATTGTAGCATTTCTT GATGTTGCTTAGTCACTTATTTCATAAACAACTTAATGTTCTGAATAATTTC TTACTAAACATTTTGTTATTGGGCAAGTGATTGAAAATAGTAAATGCTTTGT GTGATTGA 120 hsCOX6c TCTTGGAATATAAAGAATTTCTTCAGGTTGAATTACCTAGAAGTTTGTCACT GACTTGTGTTCCTGAACTATGACACATGAATATGTGGGCTAAGAAATAGTT CCTCTTGATAAATAAACAATTAACAAATACTTTGGACAGTAAGTCTTTCTCA GTTCTTAATGATAATGCAGGGCACTTACTAGCATAAGAATTGGTTTGGGAT TTAACTGTTTATGAAGCTAACTTGATTTCCGTGTTTTGTTAAAATTTCATTG TTCTAGCACATCTTTAACTGTGATAGTT 121 hsIRP1 GAGACGTGCACTTGGTCGTGCGCCCAGGGAGGAAGCCGCACCACCAGC CAGCGCAGGCCCTGGTGGAGAGGCCTCCCTGGCTGCCTCTGGGAGGGG TGCTGCCTTGTAGATGGAGCAAGTGAGCACTGAGGGTCTGGTGCCAATC CTGTAGGCACAAAACCAGAAGTTTCTACATTCTCTATTTTTGTTAATCATCT TCTCTTTTTCCAGAATTTGGAAGCTAGAATGGTGGGAATGTCAGTAGTGC CAGAAAGAGAGAACCAAGCTTGTCTTTAAAGTTACTGATCACAGGACGTT GCTTTTTCACTGTTTCCTATTAATCTTCAGCTGAACACAAGCAAACCTTCT CAGGAGGTGTCTCCTACCCTCTTATTGTTCCTCTTACGCTCTGCTCAATGA AACCTTCCTCTTGAGGGTCATTTTCCTTTCTGTATTAATTATACCAGTGTTA AGTGACATAGATAAGAACTTTGCACACTTCAAATCAGAGCAGTGATTCTCT CTTCTCTCCCCTTTTCCTTCAGAGTGAATCATCCAGACTCCTCATGGATAG GTCGGGTGTTAAAGTTGTTTTGATTATGTACCTTTTGATAGATCCACATAA AAAGAAATGTGAAGTTTTCTTTTACTATCTTTTCATTTATCAAGCAGAGACC TTTGTTGGGAGGCGGTTTGGGAGAACACATTTCTAATTTGAATGAAATGAA ATCTATTTTCAGTG 122 hsMRPS12 CAGAAGAAGTGACGGCTGGGGGCACAGTGGGCTGGGCGCCCCTGCAGA ACATGAACCTTCCGCTCCTGGCTGCCACAGGGTCCTCCGATGCTGGCCT TTGCGCCTCTAGAGGCAGCCACTCATGGATTCAAGTCCTGGCTCCGCCT CTTCCATCAGGACCACT 123 hsATP5J2 AGAGGACACACTCTGCACCCCCCCACCCCACGACCTTGGCCCGAGCCCC TCCGTGAGGAA 124 mSOD2 AGCCCTTCCGCCAGGCTGTGTGTCAGGCCCGTGGTGGGTGTTTTGTAGT AGTGTAGAGCATTGCA 125 hsOXA1L CTTATGTTCTGTGCGCATTCTGGCAGGAATTCTGTCTCTTCAGAGACTCAT CCTCAAAACAAGACTTGACACTGTGTCCTTGCCCCAGTCCTAGGAACTGT GGCACACAGAGATGTTCATTTTAAAAACGGATTTCATGAAACACTCTTGTA CTTATGTTTATAAGAGAGCACTGGGTAGCCAAGTGATCTTCCCATTCACA GAGTTAGTAAACCTCTGTACTACATGCTG 126 MTS- MAASPHTLSSRLLTGCVGGSVWYLERRT COX10 127 MTS- MSVLTRLLLRGLTRLGSAAPVRRARIHSL COX8 128 MTS- MWRLRRAAVA OPA1 129 hsCOX10 MAASPHTLSSRLLTGCVGGSVWYLERRT 130 scRPM2 MAFKSFIYSKGYHRSAAQKKTATSFFDSSYQYLRQNQGLVNSDPVLHASHLH PHPVVVANVNYNNVDDILHPHDLDSSINNTNNPLTHEELLYNQNVSLRSLKQ QQSTNYVNNNNNNQHRYY 131 IcSirt5 MRKRSLRCHLVVSANASLSPRKDEVTSRKESENLVKGKKNKKSHLHLLLFTAS KIGTDSVFDVQKSKECCKELGLLFTSLIHSIGSFPFDEEPKAAAVFLPGSLPQL TVLVLAPGSGSCPTGKSTPHLAASGRNAELLRPQNSMIVRQFTCRGTISSHL CAHLRKPHDSRNMARP 132 tbNDUS7 MLRRTSFNFTGRAMISRGSPEWSHRLDLKKGKKTTMMHKLGTSKPNNALQY AQMTL 133 ncQCR2 MISRSALSRGSQLALRRPAAAKTAQRGFAAAAASPAASYEPTTIAG 134 hsATP5G2 MPELILYVAITLSVAERLVGPGHACAEPSFRSSRCSAPLCLLCSGSSSPATAP HPLKMFACSKFVSTPSLVKSTSQLLSRPLSAVVLKRPEILTDESLSSLAVSCPL TSLVSSRSFQTSAISRDIDTA 135 hsLACTB MYRLMSAVTARAAAPGGLASSCGRRGVHQRAGLPPLGHGVVVGGLGLGLGL ALGVKLAGGLRGAAPAQSPAAPDPEASPLAEPPQEQSLAPWSPQTPAPPCS RCFARAIESSRDLL 136 spilv1 MTVLAPLRRLHTRAAFSSYGREIALQKRFLNLNSCSAVRRYGTGFSNNLRIKK LKNAFGVVRANSTKSTSTVTTASPIKYDSSFVGKTGGEIFHDMMLKHNVKHV FGYPGGAILPVFDAIYRSPHFEFILPRHEQAAGHA 137 gmCOX2 MILCPLEAFIVQHILTISVMGLLSCFRSTVLRKCSKGSSGMSRFLYTNNFQRNL ISSGGNESYYGYFNRRSYTSLYMGTGTVGGITSARIRVPNVGCEGFMCSSHL SITQRNSRLIHSTSKIVPN 138 crATP6 MALQQAAPRVFGLLGRAPVALGQSGILTGSSGFKNQGFNGSLQSVENHVYA QAFSTSSQEEQAAPSIQGASGMKLPGMAGSMLLGKSRSGLRTGSMVPFAA QQAMNM 139 hsOPA1 MVVRLRRAAVACEVCQSLVKHSSGIKGSLPLQKLHLVSRSIYHSHHPTLKLQR PQLRTSFQQFSSLTNLPLRKLKFSPIKYGYQPRRN 140 hsSDHD MAVLWRLSAVCGALGGRALLLRTPVVRPAHISAFLQDRPIPEWCGVQHIHLS PSHH 141 hsADCK3 MAAILGDTIMVAKGLVKLTQAAVETHLQHLGIGGELIMAARALQSTAVEQIGM FLGKVQGQDKHEEYFAENFGGPEGEFHFSVPHAAGASTDFSSASAPDQSAP PSLGHAHSEGPAPAYVASGPFREAGFPGQASSPLGRANGRLFANPRDSFSA MGFQRRF 142 osP0644B06. MALLLRHSPKLRRAHAILGCERGTVVRHFSSSTCSSLVKEDTVSSSNLHPEY 24-2 AKKIGGSDFSHDRQSGKELQNFKVSPQEASRASNFMRASKYGMPITANGVH SLFSCGQVVPSRCF 143 Neurospora MASTRVLASRLASQMAASAKVARPAVRVAQVSKRTIQTGSPLQTLKRTQMT crassa SIVNATTRQAFQKRA ATP9 (ncATP9) 144 hsGHITM MLAARLVCLRTLPSRVFHPAFTKASPVVKNSITKNQVVLLTPSRE 145 hsNDUFA MASRVLSAYVSRLPAAFAPLPRVRMLAVARPLSTALCSAGTQTRLGTLQPAL B1 VLAQVPGRVTQLCRQY 146 hsATP5G3 MFACAKLACTPSLIRAGSRVAYRPISASVLSRPEASRTGEGSTVFNGAQNGV SQLIQREFQTSAISR 147 crATP6_ MALQQAAPRVFGLLGRAPVALGQSGILTGSSGFKNQGFNGSLQSVENHVYA hsADCK3 QAFSTSSQEEQAAPSIQGASGMKLPGMAGSMLLGKSRSGLRTGSMVPFAA QQAMNMGGMAAILGDTIMVAKGLVKLTQAAVETHLQHLGIGGELIMAARALQ STAVEQIGMFLGKVQGQDKHEEYFAENFGGPEGEFHFSVPHAAGASTDFSS ASAPDQSAPPSLGHAHSEGPAPAYVASGPFREAGFPGQASSPLGRANGRLF ANPRDSFSAMGFQRRFGG 148 ncATP9_ MASTRVLASRLASQMAASAKVARPAVRVAQVSKRTIQTGSPLQTLKRTQMT ncATP9 SIVNATTRQAFQKRAMASTRVLASRLASQMAASAKVARPAVRVAQVSKRTIQ TGSPLQTLKRTQMTSIVNATTRQAFQKRA 149 zmLOC100282174 MALLRAAVSELRRRGRGALTPLPALSSLLSSLSPRSPASTRPEPNNPHADRR HVIALRRCPPLPASAVLAPELLHARGLLPRHVVSHASPLSTSSSSSRPADKAQ LTVVVDKWIPEAARPY 150 ncATP9_ MASTRVLASRLASQMAASAKVARPAVRVAQVSKRTIQTGSPLQTLKRTQMT zmLOC100282174_ SIVNATTRQAFQKRAMALLRAAVSELRRRGRGALTPLPALSSLLSSLSPRSPA spilv1_ STRPEPNNPHADRRHVIALRRCPPLPASAVLAPELLHARGLLPRHWSHASPL ncATP9 STSSSSSRPADKAQLTWVDKWIPEAARPYMTVLAPLRRLHTRAAFSSYGREI ALQKRFLNLNSCSAVRRYGTGFSNNLRIKKLKNAFGVVRANSTKSTSTVTTA SPIKYDSSFVGKTGGEIFHDMMLKHNVKHVFGYPGGAILPVFDAIYRSPHFEF ILPRHEQAAGHAMASTRVLASRLASQMAASAKVARPAVRVAQVSKRTIQTGS PLQTLKRTQMTSIVNATTRQAFQKRA 151 zmLOC100282174_ MALLRAAVSELRRRGRGALTPLPALSSLLSSLSPRSPASTRPEPNNPHADRR hsADCK3_ HVIALRRCPPLPASAVLAPELLHARGLLPRHVVSHASPLSTSSSSSRPADKAQ crATP6_ LTWVDKWIPEAARPYMAAILGDTIMVAKGLVKLTQAAVETHLQHLGIGGELIM hsATP5G3 AARALQSTAVEQIGMFLGKVQGQDKHEEYFAENFGGPEGEFHFSVPHAAGA STDFSSASAPDQSAPPSLGHAHSEGPAPAYVASGPFREAGFPGQASSPLGR ANGRLFANPRDSFSAMGFQRRFMALQQAAPRVFGLLGRAPVALGQSGILTG SSGFKNQGFNGSLQSVENHVYAQAFSTSSQEEQAAPSIQGASGMKLPGMA GSMLLGKSRSGLRTGSMVPFAAQQAMNMMFACAKLACTPSLIRAGSRVAYR PISASVLSRPEASRTGEGSTVFNGAQNGVSQLIQREFQTSAISR 152 zmLOC100282174_ MALLRAAVSELRRRGRGALTPLPALSSLLSSLSPRSPASTRPEPNNPHADRR hsADCK3_ HVIALRRCPPLPASAVLAPELLHARGLLPRHVVSHASPLSTSSSSSRPADKAQ hsATP5G3 LTWVDKWIPEAARPYMAAILGDTIMVAKGLVKLTQAAVETHLQHLGIGGELIM AARALQSTAVEQIGMFLGKVQGQDKHEEYFAENFGGPEGEFHFSVPHAAGA STDFSSASAPDQSAPPSLGHAHSEGPAPAYVASGPFREAGFPGQASSPLGR ANGRLFANPRDSFSAMGFQRRFMFACAKLACTPSLIRAGSRVAYRPISASVL SRPEASRTGEGSTVFNGAQNGVSQLIQREFQTSAISR 153 ncATP9_ MASTRVLASRLASQMAASAKVARPAVRVAQVSKRTIQTGSPLQTLKRTQMT zmLOC100282174 SIVNATTRQAFQKRAMALLRAAVSELRRRGRGALTPLPALSSLLSSLSPRSPA STRPEPNNPHADRRHVIALRRCPPLPASAVLAPELLHARGLLPRHWSHASPL STSSSSSRPADKAQLTWVDKWIPEAARPY 154 hsADCK3_ MAAILGDTIMVAKGLVKLTQAAVETHLQHLGIGGELIMAARALQSTAVEQIGM zmLOC150282174_ FLGKVQGQDKHEEYFAENFGGPEGEFHFSVPHAAGASTDFSSASAPDQSAP crATP6_ PSLGHAHSEGPAPAYVASGPFREAGFPGQASSPLGRANGRLFANPRDSFSA hsATP5G3 MGFQRRFMALLRAAVSELRRRGRGALTPLPALSSLLSSLSPRSPASTRPEPN NPHADRRHVIALRRCPPLPASAVLAPELLHARGLLPRHWSHASPLSTSSSSS RPADKAQLTWVDKWIPEAARPYMALQQAAPRVFGLLGRAPVALGQSGILTG SSGFKNQGFNGSLQSVENHVYAQAFSTSSQEEQAAPSIQGASGMKLPGMA GSMLLGKSRSGLRTGSMVPFAAQQAMNMMFACAKLACTPSLIRAGSRVAYR PISASVLSRPEASRTGEGSTVFNGAQNGVSQLIQREFQTSAISR 155 crATP6_ MALQQAAPRVFGLLGRAPVALGQSGILTGSSGFKNQGFNGSLQSVENHVYA hsADCK3_ QAFSTSSQEEQAAPSIQGASGMKLPGMAGSMLLGKSRSGLRTGSMVPFAA zmLOC150282174_ QQAMNMMAAILGDTIMVAKGLVKLTQAAVETHLQHLGIGGELIMAARALQST hsATP5G3 AVEQIGMFLGKVQGQDKHEEYFAENFGGPEGEFHFSVPHAAGASTDFSSAS APDQSAPPSLGHAHSEGPAPAYVASGPFREAGFPGQASSPLGRANGRLFA NPRDSFSAMGFQRRFMALLRAAVSELRRRGRGALTPLPALSSLLSSLSPRSP ASTRPEPNNPHADRRHVIALRRCPPLPASAVLAPELLHARGLLPRHWSHASP LSTSSSSSRPADKAQLTWVDKWIPEAARPYMFACAKLACTPSLIRAGSRVAY RPISASVLSRPEASRTGEGSTVFNGAQNGVSQLIQREFQTSAISR 156 hsADCK3_ MAAILGDTIMVAKGLVKLTQAAVETHLQHLGIGGELIMAARALQSTAVEQIGM zmLOC100282174 FLGKVQGQDKHEEYFAENFGGPEGEFHFSVPHAAGASTDFSSASAPDQSAP PSLGHAHSEGPAPAYVASGPFREAGFPGQASSPLGRANGRLFANPRDSFSA MGFQRRFGGMALLRAAVSELRRRGRGALTPLPALSSLLSSLSPRSPASTRP EPNNPHADRRHVIALRRCPPLPASAVLAPELLHARGLLPRHWSHASPLSTSS SSSRPADKAQLTWVDKWIPEAARPYGG 157 hsADCK3_ MAAILGDTIMVAKGLVKLTQAAVETHLQHLGIGGELIMAARALQSTAVEQIGM zmLOC150282174_ FLGKVQGQDKHEEYFAENFGGPEGEFHFSVPHAAGASTDFSSASAPDQSAP crATP6 PSLGHAHSEGPAPAYVASGPFREAGFPGQASSPLGRANGRLFANPRDSFSA MGFQRRFGGMALLRAAVSELRRRGRGALTPLPALSSLLSSLSPRSPASTRP EPNNPHADRRHVIALRRCPPLPASAVLAPELLHARGLLPRHWSHASPLSTSS SSSRPADKAQLTwVDKWIPEAARPYGGMALQQAAPRVFGLLGRAPVALGQ SGILTGSSGFKNQGFNGSLQSVENHVYAQAFSTSSQEEQAAPSIQGASGMK LPGMAGSMLLGKSRSGLRTGSMVPFAAQQAMNMGG 158 ncATP9_ MASTRVLASRLASQMAASAKVARPAVRVAQVSKRTIQTGSPLQTLKRTQMT zmLOC100282174_ SIVNATTRQAFQKRAMALLRAAVSELRRRGRGALTPLPALSSLLSSLSPRSPA spilv1_ STRPEPNNPHADRRHVIALRRCPPLPASAVLAPELLHARGLLPRHWSHASPL GNFP_ncATP9 STSSSSSRPADKAQLTWVDKWIPEAARPYMTVLAPLRRLHTRAAFSSYGREI ALQKRFLNLNSCSAVRRYGTGFSNNLRIKKLKNAFGVVRANSTKSTSTVTTA SPIKYDSSFVGKTGGEIFHDMMLKHNVKHVFGYPGGAILPVFDAIYRSPHFEF ILPRHEQAAGHAVSGEGDATYGKLTLKFICTTGKLPVPWPTLVTTLTYGVQCF SRYPDHMKQHDFFKSAMPEGYVQERTIFFKDDGNYKTRAEVKFEGDTLVNR IELKGIDFKEDGNILGHKLEYNYNSHNVYIMADKQKNGIKVNFKIRHNIEDGSV QLADHYQQNTPIGDGPVLLPDNHYLSTQSALSKDPNEMASTRVLASRLASQ MAASAKVARPAVRVAQVSKRTIQTGSPLQTLKRTQMTSIVNATTRQAFQKRA 159 ncATP9_ MASTRVLASRLASQMAASAKVARPAVRVAQVSKRTIQTGSPLQTLKRTQMT
zmLOC100282174_ SIVNATTRQAFQKRAMALLRAAVSELRRRGRGALTPLPALSSLLSSLSPRSPA spilv1_ STRPEPNNPHADRRHVIALRRCPPLPASAVLAPELLHARGLLPRHWSHASPL IcSirt5_ STSSSSSRPADKAQLTWVDKWIPEAARPYMTVLAPLRRLHTRAAFSSYGREI osP0644B06.24- ALQKRFLNLNSCSAVRRYGTGFSNNLRIKKLKNAFGVVRANSTKSTSTVTTA 2_hsATP5 SPIKYDSSFVGKTGGEIFHDMMLKHNVKHVFGYPGGAILPVFDAIYRSPHFEF G2_ncATP9 ILPRHEQAAGHAMRKRSLRCHLWSANASLSPRKDEVTSRKESENLVKGKKN KKSHLHLLLFTASKIGTDSVFDVQKSKECCKELGLLFTSLIHSIGSFPFDEEPK AAAVFLPGSLPQLTVLVLAPGSGSCPTGKSTPHLAASGRNAELLRPQNSMIV RQFTCRGTISSHLCAHLRKPHDSRNMARPMALLLRHSPKLRRAHAILGCERG TVVRHFSSSTCSSLVKEDTVSSSNLHPEYAKKIGGSDFSHDRQSGKELQNFK VSPQEASRASNFMRASKYGMPITANGVHSLFSCGQVVPSRCFMPELILYVAI TLSVAERLVGPGHACAEPSFRSSRCSAPLCLLCSGSSSPATAPHPLKMFACS KFVSTPSLVKSTSQLLSRPLSAVVLKRPEILTDESLSSLAVSCPLTSLVSSRSF QTSAISRDIDTAMASTRVLASRLASQMAASAKVARPAVRVAQVSKRTIQTGS PLQTLKRTQMTSIVNATTRQAFQKRA 160 ND4 MLKLIVPTIMLLPLTVVLSKKHMIWINTTTHSLIISIIPLLFFNQINNNLFSCSPTFS SDPLTTPLLMLTTVVLLPLTIMASQRHLSSEPLSRKKLYLSMLISLQISLIMTFTA TELIMFYIFFETTLIPTLAIITRWGNQPERLNAGTYFLFYTLVGSLPLLIALIYTHN TLGSLNILLLTLTAQELSNSWANNLMWLAYTMAFMVKMPLYGLHLWLPKAHV EAPIAGSMVLAAVLLKLGGYGMMRLTLILNPLTKHMAYPFLVLSLWGMIMTSS ICLRQTDLKSLIAYSSISHMALVVTAILIQTPVVSFTGAVILMIAHGLTSSLLFCLA NSNYERTHSRIMILSQGLQTLLPLMAFWWLLASLANLALPPTINLLGELSVLVT TFSVVSNITLLLTGLNMLVTALYSLYMFTTTQWGSLTHHINNMKPSFTRENTLM FMHLSPILLLSLNPDIITGFSS 161 ND6 MMYALFLLSVGLVMGFVGFSSKPSPIYGGLVLIVSGVVGCVIILNFGGGYMGL MVFLIYLGGMMVVFGYTTAMAIEEYPEAWGSGVEVLVSVLVGLAMEVGLVL WVKEYDGVVVVVNFNSVGSVVMIYEGEGSGLIREDPIGAGALYDYGRWLVVV TGVVTLFVGVYIVIEIARGN 162 ND1 MPMANLLLLIVPILIAMAFLMLTERKILGYMQLRKGPNVVGPYGLLQPFADAM KLFTKEPLKPATSTITLYITAPTLALTIALLLWTPLPMPNPLVNLNLGLLFILATSS LAVYSILWSGWASNSNYALIGALRAVAQTISYEVTLAIILLSTLLMSGSFNLSTLI TTQEHLVVLLLPSVVPLAMMWFISTLAETNRTPFDLAEGESELVSGFNIEYAAG PFALFFMAEYTNIIMMNTLTTTIFLGTTYDALSPELYTTYFVTKTLLLTSLFLWIR TAYPRFRYDQLMHLLVVKNFLPLTLALLMWYVSMPITISSIPPQT 163 ND1 ATACCCATGGCCAACCTCCTACTCCTCATTGTACCCATTCTAATCGCAATG [homo GCATTCCTAATGCTTACCGAACGAAAAATTCTAGGCTATATACAACTACGC sapiens] AAAGGCCCCAACGTTGTAGGCCCCTACGGGCTACTACAACCCTTCGCTG ACGCCATAAAACTCTTCACCAAAGAGCCCCTAAAACCCGCCACATCTACC ATCACCCTCTACATCACCGCCCCGACCTTAGCTCTCACCATCGCTCTTCT ACTATGAACCCCCCTCCCCATACCCAACCCCCTGGTCAACCTCAACCTAG GCCTCCTATTTATTCTAGCCACCTCTAGCCTAGCCGTTTACTCAATCCTCT GATCAGGGTGAGCATCAAACTCAAACTACGCCCTGATCGGCGCACTGCG AGCAGTAGCCCAAACAATCTCATATGAAGTCACCCTAGCCATCATTCTACT ATCAACATTACTAATAAGTGGCTCCTTTAACCTCTCCACCCTTATCACAAC ACAAGAACACCTCTGATTACTCCTGCCATCATGACCCTTGGCCATAATATG ATTTATCTCCACACTAGCAGAGACCAACCGAACCCCCTTCGACCTTGCCG AAGGGGAGTCCGAACTAGTCTCAGGCTTCAACATCGAATACGCCGCAGG CCCCTTCGCCCTATTCTTCATAGCCGAATACACAAACATTATTATAATAAA CACCCTCACCACTACAATCTTCCTAGGAACAACATATGACGCACTCTCCC CTGAACTCTACACAACATATTTTGTCACCAAGACCCTACTTCTAACCTCCC TGTTCTTATGAATTCGAACAGCATACCCCCGATTCCGCTACGACCAACTC ATACACCTCCTATGAAAAAACTTCCTACCACTCACCCTAGCATTACTTATA TGATATGTCTCCATACCCATTACAATCTCCAGCATTCCCCCTCAAACCTAA
Adeno-Associated Virus (AAV)
[0037] Adeno-associated virus (AAV) is a small virus that infects humans and some other primate species. The compositions disclosed herein comprises firstly an adeno-associated virus (AAV) genome or a derivative thereof.
[0038] An AAV genome is a polynucleotide sequence which encodes functions needed for production of an AAV viral particle. These functions include those operating in the replication and packaging cycle for AAV in a host cell, including encapsidation of the AAV genome into an AAV viral particle. Naturally occurring AAV viruses are replication-deficient and rely on the provision of helper functions in trans for completion of a replication and packaging cycle. Accordingly, the AAV genome of the vector of the invention is typically replication-deficient.
[0039] The AAV genome can be in single-stranded form, either positive or negative-sense, or alternatively in double-stranded form. The use of a double-stranded form allows bypass of the DNA replication step in the target cell and so can accelerate transgene expression.
[0040] The AAV genome may be from any naturally derived serotype or isolate or Glade of AAV. Thus, the AAV genome may be the full genome of a naturally occurring AAV virus. As is known to the skilled person, AAV viruses occurring in nature may be classified according to various biological systems.
[0041] Commonly, AAV viruses are referred to in terms of their serotype. A serotype corresponds to a variant subspecies of AAV which owing to its profile of expression of capsid surface antigens has a distinctive reactivity which can be used to distinguish it from other variant subspecies. Typically, a virus having a particular AAV serotype does not efficiently cross-react with neutralising antibodies specific for any other AAV serotype. AAV serotypes include AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, AAV12, AAV13, AAV14, AAV15, and AAV16, also recombinant serotypes, such as Rec2 and Rec3, recently identified from primate brain. In some embodiments, the AAV viruses comprising the recombinant nucleic acid of the disclosure has a serotype selected from the group consisting of AAV2, AAV5, AAV7, AAV8, AAV9, AAV10, AAV-DJ, and a combination thereof.
[0042] A preferred serotype of AAV for use in the invention is AAV2. Other serotypes of particular interest for use in the invention include AAV4, AAV5 and AAV8 which efficiently transduce tissue in the eye, such as the retinal pigmented epithelium. The serotype of AAV which is used can be an AAV serotype which is not AAV4. Reviews of AAV serotypes may be found in Choi et al (Curr Gene Ther. 2005; 5(3); 299-310) and Wu et al (Molecular Therapy. 2006; 14(3), 316-327). The sequences of AAV genomes or of elements of AAV genomes including ITR sequences, rep or cap genes for use in the invention may be derived from the following accession numbers for AAV whole genome sequences: Adeno-associated virus 1 NC_002077, AF063497; Adeno-associated virus 2 NC_001401; Adeno-associated virus 3 NC 001729; Adeno-associated virus 3B NC_001863; Adeno-associated virus 4 NC_001829; Adeno-associated virus 5 Y18065, AF085716; Adeno-associated virus 6 NC_001862; Avian AAV ATCC VR-865 AY186198, AY629583, NC_004828; Avian AAV strain DA-1 NC_006263, AY629583; Bovine AAV NC_005889, AY388617.
[0043] AAV viruses may also be referred to in terms of clades or clones. This refers to the phylogenetic relationship of naturally derived AAV viruses, and typically to a phylogenetic group of AAV viruses which can be traced back to a common ancestor, and includes all descendants thereof. Additionally, AAV viruses may be referred to in terms of a specific isolate, i.e. a genetic isolate of a specific AAV virus found in nature. The term genetic isolate describes a population of AAV viruses which has undergone limited genetic mixing with other naturally occurring AAV viruses, thereby defining a recognisably distinct population at a genetic level.
[0044] Examples of clades and isolates of AAV that may be used in the invention include: Clade A: AAV1 NC_002077, AF063497, AAV6 NC_001862, Hu. 48 AY530611, Hu 43 AY530606, Hu 44 AY530607, Hu 46 AY530609; Clade B: Hu. 19 AY530584, Hu. 20 AY530586, Hu 23 AY530589, Hu22 AY530588, Hu24 AY530590, Hu21 AY530587, Hu27 AY530592, Hu28 AY530593, Hu 29 AY530594, Hu63 AY530624, Hu64 AY530625, Hu13 AY530578, Hu56 AY530618, Hu57 AY530619, Hu49 AY530612, Hu58 AY530620, Hu34 AY530598, Hu35 AY530599, AAV2 NC_001401, Hu45 AY530608, Hu47 AY530610, Hu51 AY530613, Hu52 AY530614, Hu T41 AY695378, Hu S17 AY695376, Hu T88 AY695375, Hu T71 AY695374, Hu T70 AY695373, Hu T40 AY695372, Hu T32 AY695371, Hu T17 AY695370, Hu LG15 AY695377; Clade C: Hu9 AY530629, Hu10 AY530576, Hu11 AY530577, Hu53 AY530615, Hu55 AY530617, Hu54 AY530616, Hu7 AY530628, Hu18 AY530583, Hu15 AY530580, Hu16 AY530581, Hu25 AY530591, Hu60 AY530622, Ch5 AY243021, Hu3 AY530595, Hu1 AY530575, Hu4 AY530602 Hu2, AY530585, Hu61 AY530623; Clade D: Rh62 AY530573, Rh48 AY530561, Rh54 AY530567, Rh55 AY530568, Cy2 AY243020, AAV7 AF513851, Rh35 AY243000, Rh37 AY242998, Rh36 AY242999, Cy6 AY243016, Cy4 AY243018, Cy3 AY243019, Cy5 AY243017, Rh13 AY243013, Clade E: Rh38 AY530558, Hu66 AY530626, Hu42 AY530605, Hu67 AY530627, Hu40 AY530603, Hu41 AY530604, Hu37 AY530600, Rh40 AY530559, Rh2 AY243007, Bb1 AY243023, Bb2 AY243022, Rh10 AY243015, Hu17 AY530582, Hu6 AY530621, Rh25 AY530557, Pi2 AY530554, Pi1 AY530553, Pi3 AY530555, Rh57 AY530569, Rh50 AY530563, Rh49 AY530562, Hu39 AY530601, Rh58 AY530570, Rh61 AY530572, Rh52 AY530565, Rh53 AY530566, Rh51 AY530564, Rh64 AY530574, Rh43 AY530560, AAV8 AF513852, Rh8 AY242997, Rh1 AY530556; Clade F: Hu14 (AAV9) AY530579, Hu31 AY530596, Hu32 AY530597, Clonal Isolate AAV5 Y18065, AF085716, AAV 3 NC_001729, AAV 3B NC_001863, AAV4 NC_001829, Rh34 AY243001, Rh33 AY243002, Rh32 AY243003.
[0045] The skilled person can select an appropriate serotype, Glade, clone or isolate of AAV for use in the present invention on the basis of their common general knowledge. For instance, the AAV5 capsid has been shown to transduce primate cone photoreceptors efficiently as evidenced by the successful correction of an inherited color vision defect (Mancuso et al., Nature 2009, 461:784-7).
[0046] It should be understood however that the invention also encompasses use of an AAV genome of other serotypes that may not yet have been identified or characterised. The AAV serotype determines the tissue specificity of infection (or tropism) of an AAV virus. Accordingly, preferred AAV serotypes for use in AAV viruses administered to patients in accordance with the invention are those which have natural tropism for or a high efficiency of infection of target cells within eye in LHON. Thus, AAV serotypes for use in AAV viruses administered to patients can be ones which infect cells of the neurosensory retina and retinal pigment epithelium.
[0047] Typically, the AAV genome of a naturally derived serotype or isolate or Glade of AAV comprises at least one inverted terminal repeat sequence (ITR). An ITR sequence acts in cis to provide a functional origin of replication, and allows for integration and excision of the vector from the genome of a cell. In preferred embodiments, one or more ITR sequences flank the polynucleotide sequence encoding ND4, ND6, or ND1 or a variant thereof. Preferred ITR sequences are those of AAV2, and variants thereof. The AAV genome typically also comprises packaging genes, such as rep and/or cap genes which encode packaging functions for an AAV viral particle. The rep gene encodes one or more of the proteins Rep78, Rep68, Rep52 and Rep40 or variants thereof. The cap gene encodes one or more capsid proteins such as VP1, VP2 and VP3 or variants thereof. These proteins make up the capsid of an AAV viral particle. Capsid variants are discussed below.
[0048] A promoter will be operably linked to each of the packaging genes. Specific examples of such promoters include the p5, p19 and p40 promoters (Laughlin et al., 1979, PNAS, 76:5567-5571). For example, the p5 and p19 promoters are generally used to express the rep gene, while the p40 promoter is generally used to express the cap gene.
[0049] As discussed above, the AAV genome used in the vector of the invention may therefore be the full genome of a naturally occurring AAV virus. For example, a vector comprising a full AAV genome may be used to prepare AAV virus in vitro. However, while such a vector may in principle be administered to patients, this will be done rarely in practice. Preferably the AAV genome will be derivatised for the purpose of administration to patients. Such derivatisation is standard in the art and the present invention encompasses the use of any known derivative of an AAV genome, and derivatives which could be generated by applying techniques known in the art. Derivatisation of the AAV genome and of the AAV capsid are reviewed in Coura and Nardi (Virology Journal, 2007, 4:99), and in Choi et al and Wu et al, referenced above.
[0050] Derivatives of an AAV genome include any truncated or modified forms of an AAV genome which allow for expression of a ND4, ND6, or ND1 transgene from a vector of the invention in vivo. Typically, it is possible to truncate the AAV genome significantly to include minimal viral sequence yet retain the above function. This is preferred for safety reasons to reduce the risk of recombination of the vector with wild-type virus, and also to avoid triggering a cellular immune response by the presence of viral gene proteins in the target cell.
[0051] Typically, a derivative will include at least one inverted terminal repeat sequence (ITR), preferably more than one ITR, such as two ITRs or more. One or more of the ITRs may be derived from AAV genomes having different serotypes, or may be a chimeric or mutant ITR. A preferred mutant ITR is one having a deletion of a trs (terminal resolution site). This deletion allows for continued replication of the genome to generate a single-stranded genome which contains both coding and complementary sequences i.e. a self-complementary AAV genome. This allows for bypass of DNA replication in the target cell, and so enables accelerated transgene expression.
[0052] The one or more ITRs will preferably flank the polynucleotide sequence encoding ND4, ND6, ND1, or a variant thereof at either end. The inclusion of one or more ITRs is preferred to aid concatamer formation of the vector of the invention in the nucleus of a host cell, for example following the conversion of single-stranded vector DNA into double-stranded DNA by the action of host cell DNA polymerases. The formation of such episomal concatamers protects the vector construct during the life of the host cell, thereby allowing for prolonged expression of the transgene in vivo.
[0053] In preferred embodiments, ITR elements will be the only sequences retained from the native AAV genome in the derivative. Thus, a derivative will preferably not include the rep and/or cap genes of the native genome and any other sequences of the native genome. This is preferred for the reasons described above, and also to reduce the possibility of integration of the vector into the host cell genome. Additionally, reducing the size of the AAV genome allows for increased flexibility in incorporating other sequence elements (such as regulatory elements) within the vector in addition to the transgene.
[0054] With reference to the AAV2 genome, the following portions could therefore be removed in a derivative of the invention: One inverted terminal repeat (ITR) sequence, the replication (rep) and capsid (cap) genes (NB: the rep gene in the wildtype AAV genome should not to be confused with ND4, ND6, or ND1, the human gene affected in LHON). However, in some embodiments, including in vitro embodiments, derivatives may additionally include one or more rep and/or cap genes or other viral sequences of an AAV genome. Naturally occurring AAV virus integrates with a high frequency at a specific site on human chromosome 19, and shows a negligible frequency of random integration, such that retention of an integrative capacity in the vector may be tolerated in a therapeutic setting.
[0055] Where a derivative genome comprises genes encoding capsid proteins i.e. VP1, VP2 and/or VP3, the derivative may be a chimeric, shuffled or capsid-modified derivative of one or more naturally occurring AAV viruses. In particular, the invention encompasses the provision of capsid protein sequences from different serotypes, clades, clones, or isolates of AAV within the same vector i.e. pseudotyping.
[0056] Chimeric, shuffled or capsid-modified derivatives will be typically selected to provide one or more desired functionalities for the viral vector. Thus, these derivatives may display increased efficiency of gene delivery, decreased immunogenicity (humoral or cellular), an altered tropism range and/or improved targeting of a particular cell type compared to an AAV viral vector comprising a naturally occurring AAV genome, such as that of AAV2. Increased efficiency of gene delivery may be effected by improved receptor or co-receptor binding at the cell surface, improved internalisation, improved trafficking within the cell and into the nucleus, improved uncoating of the viral particle and improved conversion of a single-stranded genome to double-stranded form. Increased efficiency may also relate to an altered tropism range or targeting of a specific cell population, such that the vector dose is not diluted by administration to tissues where it is not needed.
[0057] Chimeric capsid proteins include those generated by recombination between two or more capsid coding sequences of naturally occurring AAV serotypes. This may be performed for example by a marker rescue approach in which non-infectious capsid sequences of one serotype are cotransfected with capsid sequences of a different serotype, and directed selection is used to select for capsid sequences having desired properties. The capsid sequences of the different serotypes can be altered by homologous recombination within the cell to produce novel chimeric capsid proteins.
[0058] Chimeric capsid proteins also include those generated by engineering of capsid protein sequences to transfer specific capsid protein domains, surface loops or specific amino acid residues between two or more capsid proteins, for example between two or more capsid proteins of different serotypes.
[0059] Shuffled or chimeric capsid proteins may also be generated by DNA shuffling or by error-prone PCR. Hybrid AAV capsid genes can be created by randomly fragmenting the sequences of related AAV genes e.g. those encoding capsid proteins of multiple different serotypes and then subsequently reassembling the fragments in a self-priming polymerase reaction, which may also cause crossovers in regions of sequence homology. A library of hybrid AAV genes created in this way by shuffling the capsid genes of several serotypes can be screened to identify viral clones having a desired functionality. Similarly, error prone PCR may be used to randomly mutate AAV capsid genes to create a diverse library of variants which may then be selected for a desired property.
[0060] The sequences of the capsid genes may also be genetically modified to introduce specific deletions, substitutions or insertions with respect to the native wild-type sequence. In particular, capsid genes may be modified by the insertion of a sequence of an unrelated protein or peptide within an open reading frame of a capsid coding sequence, or at the N- and/or C-terminus of a capsid coding sequence.
[0061] The unrelated protein or peptide may advantageously be one which acts as a ligand for a particular cell type, thereby conferring improved binding to a target cell or improving the specificity of targeting of the vector to a particular cell population. An example might include the use of RGD peptide to block uptake in the retinal pigment epithelium and thereby enhance transduction of surrounding retinal tissues (Cronin et al., 2008 ARVO Abstract: D1048). The unrelated protein may also be one which assists purification of the viral particle as part of the production process i.e. an epitope or affinity tag. The site of insertion will typically be selected so as not to interfere with other functions of the viral particle e.g. internalisation, trafficking of the viral particle. The skilled person can identify suitable sites for insertion based on their common general knowledge. Particular sites are disclosed in Choi et al, referenced above.
[0062] The invention additionally encompasses the provision of sequences of an AAV genome in a different order and configuration to that of a native AAV genome. The invention also encompasses the replacement of one or more AAV sequences or genes with sequences from another virus or with chimeric genes composed of sequences from more than one virus. Such chimeric genes may be composed of sequences from two or more related viral proteins of different viral species.
[0063] The vector of the invention takes the form of a polynucleotide sequence comprising an AAV genome or derivative thereof and a sequence encoding ND4, ND6, ND1 or a variant thereof.
[0064] For the avoidance of doubt, the invention also provides an AAV viral particle comprising a vector of the invention. The AAV particles of the invention include transcapsidated forms wherein an AAV genome or derivative having an ITR of one serotype is packaged in the capsid of a different serotype. The AAV particles of the invention also include mosaic forms wherein a mixture of unmodified capsid proteins from two or more different serotypes makes up the viral envelope. The AAV particle also includes chemically modified forms bearing ligands adsorbed to the capsid surface. For example, such ligands may include antibodies for targeting a particular cell surface receptor.
[0065] The invention additionally provides a host cell comprising a vector or AAV viral particle of the invention.
[0066] Recombinant Nucleic Acid Sequences
[0067] Also disclosed herein are recombinant nucleic acid sequences comprising a polynucleotide sequence encoding a NADH dehydrogenase subunit-4 (ND4), NADH dehydrogenase subunit-1 (ND1) and NADH dehydrogenase subunit-6 (ND6) polypeptide or a variant thereof.
[0068] The polynucleotide sequence for ND4 is shown in SEQ ID NO: 6 and encodes the protein shown in SEQ ID NO: 160. Further nucleic acid sequences for ND4 are SEQ ID NO: 7 and 8. The polynucleotide sequence for ND6 is shown in SEQ ID NO: 9 and encodes the protein shown in SEQ ID NO: 161. A further nucleic acid sequence for ND6 is SEQ ID NO: 10. The polynucleotide sequence for ND1 is shown in SEQ ID NO: 11 and encodes the protein shown in SEQ ID NO: 162. A further nucleic acid sequence for ND1 is SEQ ID NO: 12.
[0069] A variant of any one of SEQ ID NO: 160, 161, or 162 may comprise truncations, mutants or homologues thereof, and any transcript variants thereof which encode a functional ND4, ND6, or ND1 polypeptide. Any homologues mentioned herein are typically at least 70% homologous to a relevant region of ND4, ND6, or ND1, and can functionally compensate for the polypeptide deficiency.
[0070] Homology can be measured using known methods. For example the UWGCG Package provides the BESTFIT program which can be used to calculate homology (for example used on its default settings) (Devereux et at (1984) Nucleic Acids Research 12, 387-395). The PILEUP and BLAST algorithms can be used to calculate homology or line up sequences (typically on their default settings), for example as described in Altschul S. F. (1993) J Mol Evol 36:290-300; Altschul, S, F et at (1990) J Mol Biol 215:403-10. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov/).
[0071] In preferred embodiments, a recombinant nucleic acid sequence may encode a polypeptide which is at least 55%, 65%, 70%, 75%, 80%, 85%, 90% and more preferably at least 95%, 97%, 99%, 99.5%, or 100% homologous to a relevant region of ND4, ND6, or ND1 (SEQ ID NO: 160, 161, or 162) over at least 20, preferably at least 30, for instance at least 40, 60, 100, 200, 300, 400 or more contiguous amino acids, or even over the entire sequence of the recombinant nucleic acid. The relevant region will be one which provides for functional activity of ND4, ND6, or ND1.
[0072] Alternatively, and preferably the recombinant nucleic acid sequence may encode a polypeptide having at least 70%, 75%, 80%, 85%, 90% and more preferably at least 95%, 97%, 99%, 99.5%, or 100% homologous to full-length ND4, ND6, or ND1 (SEQ ID NO: 160, 161, or 162) over its entire sequence. Typically the recombinant nucleic acid sequence differs from the relevant region of ND4, ND6, or ND1 (SEQ ID NO: 160, 161, or 162) by at least, or less than, 2, 5, 10, 20, 40, 50 or 60 mutations (each of which can be substitutions, insertions or deletions).
[0073] A recombinant nucleic acid ND4, ND6, or ND1 polypeptide may have a percentage identity with a particular region of SEQ ID NO: 160, 161, or 162 which is the same as any of the specific percentage homology values (i.e. it may have at least 70%, 80% or 90% and more preferably at least 95%, 97%, 99% identity) across any of the lengths of sequence mentioned above.
[0074] Variants of ND4, ND6, or ND1 (SEQ ID NO: 160, 161, or 162) also include truncations. Any truncation may be used so long as the variant is still functional. Truncations will typically be made to remove sequences that are non-essential for the protein activity and/or do not affect conformation of the folded protein, in particular folding of the active site. Appropriate truncations can routinely be identified by systematic truncation of sequences of varying length from the N- or C-terminus. Preferred truncations are N-terminal and may remove all other sequences except for the catalytic domain.
[0075] Variants of ND4, ND6, or ND1 (SEQ ID NO: 160, 161, or 162) further include mutants which have one or more, for example, 2, 3, 4, 5 to 10, 10 to 20, 20 to 40 or more, amino acid insertions, substitutions or deletions with respect to a particular region of ND4, ND6, or ND1 (SEQ ID NO: 160, 161, or 162). Deletions and insertions are made preferably outside of the catalytic domain as described below. Substitutions are also typically made in regions that are non-essential for protease activity and/or do not affect conformation of the folded protein.
[0076] Substitutions preferably introduce one or more conservative changes, which replace amino acids with other amino acids of similar chemical structure, similar chemical properties or similar side-chain volume. The amino acids introduced may have similar polarity, hydrophilicity, hydrophobicity, basicity, acidity, neutrality or charge to the amino acids they replace. Alternatively, the conservative change may introduce another amino acid that is aromatic or aliphatic in the place of a pre-existing aromatic or aliphatic amino acid. Conservative amino acid changes are well known in the art and may be selected in accordance with the properties of the amino acids.
[0077] Similarly, preferred variants of the polynucleotide sequence of ND4, ND6, or ND1 (SEQ ID NO: 6, 9, or 11) include polynucleotides having at least 70%, 75%, 80%, 85%, 90% and more preferably at least 95%, 96%, 97%, 98%, 99%, or 99.5% homologous to a relevant region of ND4, ND6, or ND1 (SEQ ID NO: 6, 9, or 11). Preferably the variant displays these levels of homology to full-length ND4, ND6, or ND1 (SEQ ID NO: 6, 9, or 11) over its entire sequence.
[0078] Mitochondrial targeting sequences (MTSs) and three prime untranslated regions (3'UTRs) can be used to target proteins or mRNA to the mitochondria. The charge, length, and structure of the MTS can be important for protein import into the mitochondria. Particular 3'UTRs may drive mRNA localization to the mitochondrial surface and thus facilitate cotranslational protein import into the mitochondria.
[0079] The polynucleotide sequence for a mitochondrial targeting sequence can encode a polypeptide selected from hsCOX10, hsCOX8, scRPM2, IcSirt5, tbNDUS7, ncQCR2, hsATP5G2, hsLACTB, spilv1, gmCOX2, crATP6, hsOPA1, hsSDHD, hsADCK3, osP0644B06.24-2, Neurospora crassa ATP9 (ncATP9), hsGHITM, hsNDUFAB1, hsATP5G3, crATP6_hsADCK3, ncATP9_ncATP9, zmLOC100282174, ncATP9_zmLOC100282174_spilv1_ncATP9, zmLOC100282174_hsADCK3_crATP6_hsATP5G3, zmLOC100282174_hsADCK3_hsATP5G3, ncATP9_zmLOC100282174, hsADCK3_zmLOC100282174_crATP6_hsATP5G3, crATP6_hsADCK3_zmLOC100282174_hsATP5G3, hsADCK3_zmLOC100282174, hsADCK3_zmLOC100282174_crATP6, ncATP9_zmLOC100282174_spilv1_GNFP_ncATP9, and ncATP9_zmLOC100282174_spilv1IcSirt5_osP0644606.24-2_hsATP5G2_ncATP9 (see Table 1 for SEQ ID NO). In one example, the polynucleotide sequences, COX10 (SEQ ID NO: 1, 2, or 3) can encode the mitochondrial targeting sequence, MTS-COX10 (SEQ ID NO: 126). In another example, the polynucleotide sequences, COX8 (SEQ ID NO: 4) can encode the mitochondrial targeting sequence, MTS-COX8 (SEQ ID NO: 127). In another example, the polynucleotide sequences, OPA1 (SEQ ID NO: 5) can encode the mitochondrial targeting sequence, MTS-OPA1 (SEQ ID NO: 128).
[0080] The 3'UTR nucleic acid sequence can be selected from hsACO2 (SEQ ID NO: 111), hsATP5B (SEQ ID NO: 112), hsAK2 (SEQ ID NO: 113), hsALDH2 (SEQ ID NO: 114), hsCOX10 (SEQ ID NO: 115), hsUQCRFS1 (SEQ ID NO: 116), hsNDUFV1 (SEQ ID NO: 117), hsNDUFV2 (SEQ ID NO: 118), hsSOD2 (SEQ ID NO: 119), hsCOX6c (SEQ ID NO: 120), hsIRP1 (SEQ ID NO: 121), hsMRPS12 (SEQ ID NO: 122), hsATP5J2 (SEQ ID NO: 123), rnSOD2 (SEQ ID NO: 124), and hsOXA1 L (SEQ ID NO: 125). The 3'UTR nucleic acid sequence can also be a variant having at least 70%, 75%, 80%, 85%, 90% and more preferably at least 95%, 96%, 97%, 98%, 99%, 99.5%, or 100% homologous to any 3'UTR nucleic acid sequence listed here. For example, the 3'UTR nucleic acid sequence can be SEQ ID NO: 13 or 14.
[0081] Also disclosed herein are recombinant nucleic acid sequences comprising a mitochondrial targeting sequence, a mitochondrial protein coding sequence, and a 3'UTR nucleic acid sequence. For example, the recombinant nucleic acid sequence can be selected from SEQ ID NO: 15-84. The recombinant nucleic acid sequence can also be a variant having at least 70%, 75%, 80%, 85%, 90% and more preferably at least 95%, 96%, 97%, 98%, 99%, 99.5%, or 100% homologous to any recombinant nucleic acid sequence listed here.
Promoters and Regulatory Sequences
[0082] The vector of the invention also includes elements allowing for the expression of the disclosed transgene in vitro or in vivo. Thus, the vector typically comprises a promoter sequence operably linked to the polynucleotide sequence encoding the ND4, ND6, or ND1 transgene or a variant thereof.
[0083] Any suitable promoter may be used. The promoter sequence may be constitutively active i.e. operational in any host cell background, or alternatively may be active only in a specific host cell environment, thus allowing for targeted expression of the transgene in a particular cell type. The promoter may show inducible expression in response to presence of another factor, for example a factor present in a host cell. In any event, where the vector is administered for therapy, the promoter must be functional in a retinal cell background.
[0084] In some embodiments, it is preferred that the promoter shows retinal-cell specific expression in order to allow for the transgene to only be expressed in retinal cell populations. Thus, expression from the promoter may be retinal-cell specific, for example confined only to cells of the neurosensory retina and retinal pigment epithelium.
[0085] Preferred promoters for the ND4, ND6, or ND1 transgene include the chicken beta-actin (CBA) promoter, optionally in combination with a cytomegalovirus (CME) enhancer element. In some cases, the preferred promoters for the ND4, ND6, or ND1 transgene comprises the CAG promoter. A particularly preferred promoter is a hybrid CBA/CAG promoter, for example the promoter used in the rAVE expression cassette. Examples of promoters based on human sequences that would induce retina specific gene expression include rhodospin kinase for rods and cones (Allocca et al., 2007, J Viol 81:11372-80), PR2.1 for cones only (Mancuso et al. 2009, Nature) and/or RPE65 for the retinal pigment epithelium (Bainbridge et al., 2008, N Eng J Med).
[0086] The vector of the invention may also comprise one or more additional regulatory sequences with may act pre- or post-transcriptionally. The regulatory sequence may be part of the native ND4, ND6, or ND1 gene locus or may be a heterologous regulatory sequence. The vector of the invention may comprise portions of the 5'UTR or 3'UTR from the native ND4, ND6, or ND1 transcript.
[0087] Regulatory sequences are any sequences which facilitate expression of the transgene i.e. act to increase expression of a transcript, improve nuclear export of mRNA or enhance its stability. Such regulatory sequences include for example enhancer elements, postregulatory elements and polyadenylation sites. A preferred polyadenylation site is the Bovine Growth Hormone poly-A signal. In the context of the vector of the invention such regulatory sequences will be cis-acting. However, the invention also encompasses the use of trans-acting regulatory sequences located on additional genetic constructs.
[0088] A preferred postregulatory element for use in a vector of the invention is the woodchuck hepatitis postregulatory element (WPRE) or a variant thereof. Another regulatory sequence which may be used in a vector of the present invention is a scaffold-attachment region (SAR). Additional regulatory sequences may be selected by the skilled person on the basis of their common general knowledge.
[0089] Preparation of Vector
[0090] The vector of the invention may be prepared by standard means known in the art for provision of vectors for gene therapy. Thus, well established public domain transfection, packaging and purification methods can be used to prepare a suitable vector preparation.
[0091] As discussed above, a vector of the invention may comprise the full genome of a naturally occurring AAV virus in addition to a polynucleotide sequence encoding ND4, ND6, or ND1 or a variant thereof. However, commonly a derivatised genome will be used, for instance a derivative which has at least one inverted terminal repeat sequence (ITR), but which may lack any AAV genes such as rep or cap.
[0092] In such embodiments, in order to provide for assembly of the derivatised genome into an AAV viral particle, additional genetic constructs providing AAV and/or helper virus functions will be provided in a host cell in combination with the derivatised genome. These additional constructs will typically contain genes encoding structural AAV capsid proteins i.e. cap, VP1, VP2, VP3, and genes encoding other functions required for the AAV life cycle, such as rep. The selection of structural capsid proteins provided on the additional construct will determine the serotype of the packaged viral vector.
[0093] A particularly preferred packaged viral vector for use in the invention comprises a derivatised genome of AAV2 in combination with AAV5 or AAV8 capsid proteins. This packaged viral vector typically comprises one or more AAV2 ITRs.
[0094] As mentioned above, AAV viruses are replication incompetent and so helper virus functions, preferably adenovirus helper functions will typically also be provided on one or more additional constructs to allow for AAV replication.
[0095] All of the above additional constructs may be provided as plasmids or other episomal elements in the host cell, or alternatively one or more constructs may be integrated into the genome of the host cell.
[0096] In these aspects, the invention provides a method for production of a vector of the invention. The method comprises providing a vector which comprises an adeno-associated virus (AAV) genome or a derivative thereof and a polynucleotide sequence encoding ND4, ND6, or ND1 or a variant thereof in a host cell, and providing means for replication and assembly of the vector into an AAV viral particle. Preferably, the method comprises providing a vector comprising a derivative of an AAV genome and a polynucleotide sequence encoding ND4, ND6, or ND1 or a variant thereof, together with one or more additional genetic constructs encoding AAV and/or helper virus functions. Typically, the derivative of an AAV genome comprises at least one ITR. Optionally, the method further comprises a step of purifying the assembled viral particles. Additionally, the method may comprise a step of formulating the viral particles for therapeutic use.
Methods of Therapy and Medical Uses
[0097] As discussed above, the present inventors have surprisingly demonstrated that a vector of the invention may be used to address the cellular dysfunction underlying LHON. In particular, they have shown that use of the vector can correct the defect associated with LHON. This provides a means whereby the degenerative process of the disease can be treated, arrested, palliated or prevented.
[0098] The invention therefore provides a method of treating or preventing LHON in a patient in need thereof, comprising administering a therapeutically effective amount of a vector of the invention to the patient by direct retinal, subretinal or intravitreal injection. Accordingly, LHON is thereby treated or prevented in the patient.
[0099] In a related aspect, the invention provides for use of a vector of the invention in a method of treating or preventing LHON by administering said vector to a patient by direct retinal, subretinal or intravitreal injection. Additionally, the invention provides the use of a vector of the invention in the manufacture of a medicament for treating or preventing LHON by direct retinal, subretinal or intravitreal injection.
[0100] In all these embodiments, the vector of the invention may be administered in order to prevent the onset of one or more symptoms of LHON. The patient may be asymptomatic. The subject may have a predisposition to the disease. The method or use may comprise a step of identifying whether or not a subject is at risk of developing, or has, LHON. A prophylactically effective amount of the vector is administered to such a subject. A prophylactically effective amount is an amount which prevents the onset of one or more symptoms of the disease.
[0101] Alternatively, the vector may be administered once the symptoms of the disease have appeared in a subject i.e. to cure existing symptoms of the disease. A therapeutically effective amount of the antagonist is administered to such a subject. A therapeutically effective amount is an amount which is effective to ameliorate one or more symptoms of the disease. Such an amount may also arrest, slow or reverse some loss of peripheral vision associated with LHON. Such an amount may also arrest, slow or reverse onset of LHON.
[0102] A typical single dose is between 1010 and 1012 genome particles, depending on the amount of remaining retinal tissue that requires transduction. A genome particle is defined herein as an AAV capsid that contains a single stranded DNA molecule that can be quantified with a sequence specific method (such as real-time PCR). That dose may be provided as a single dose, but may be repeated for the fellow eye or in cases where vector may not have targeted the correct region of retina for whatever reason (such as surgical complication). The treatment is preferably a single permanent treatment for each eye, but repeat injections, for example in future years and/or with different AAV serotypes may be considered.
[0103] The invention also provides a method of monitoring treatment or prevention of LHON in a patient comprising measuring activity ex vivo in retinal cells obtained from said patient following administration of the AAV vector of the invention by direct retinal, subretinal or intravitreal injection. This method can allow for determination of the efficacy of treatment.
Pharmaceutical Compositions
[0104] The vector of the invention can be formulated into pharmaceutical compositions. These compositions may comprise, in addition to the vector, a pharmaceutically acceptable excipient, carrier, buffer, stabiliser or other materials well known to those skilled in the art. Such materials should be non-toxic and should not interfere with the efficacy of the active ingredient. The precise nature of the carrier or other material may be determined by the skilled person according to the route of administration, i.e. here direct retinal, subretinal or intravitreal injection.
[0105] The pharmaceutical composition is typically in liquid form. Liquid pharmaceutical compositions generally include a liquid carrier such as water, petroleum, animal or vegetable oils, mineral oil or synthetic oil. Physiological saline solution, magnesium chloride, dextrose or other saccharide solution or glycols such as ethylene glycol, propylene glycol or polyethylene glycol may be included. In some cases, a surfactant, such as pluronic acid (PF68) 0.001% may be used.
[0106] In some embodiments, the pharmaceutical composition of the disclosure comprises between 109 and 1016 viral vectors. In some embodiments, the pharmaceutical composition of the disclosure comprises between 1010 and 1012 viral vectors per milliliter.
[0107] For injection at the site of affliction, the active ingredient will be in the form of an aqueous solution which is pyrogen-free and has suitable pH, isotonicity and stability. Those of relevant skill in the art are well able to prepare suitable solutions using, for example, isotonic vehicles such as Sodium Chloride Injection, Ringer's Injection, Lactated Ringer's Injection. Preservatives, stabilisers, buffers, antioxidants and/or other additives may be included, as required.
[0108] For delayed release, the vector may be included in a pharmaceutical composition which is formulated for slow release, such as in microcapsules formed from biocompatible polymers or in liposomal carrier systems according to methods known in the art.
[0109] Samples
[0110] Samples that are suitable for use in the methods described herein can be nucleic acid samples from a subject. A "nucleic acid sample" as used herein can include RNA or DNA, or a combination thereof. In another embodiment, a "polypeptide sample" (e.g., peptides or proteins, or fragments therefrom) can be used to ascertain information that an amino acid change has occurred, which is the result of a genetic variant. Nucleic acids and polypeptides can be extracted from one or more samples including but not limited to, blood, saliva, urine, mucosal scrapings of the lining of the mouth, expectorant, serum, tears, skin, tissue, or hair. A nucleic acid sample can be assayed for nucleic acid information. "Nucleic acid information," as used herein, includes a nucleic acid sequence itself, the presence/absence of genetic variation in the nucleic acid sequence, a physical property which varies depending on the nucleic acid sequence (e.g., Tm), and the amount of the nucleic acid (e.g., number of mRNA copies). A "nucleic acid" means any one of DNA, RNA, DNA including artificial nucleotides, or RNA including artificial nucleotides. As used herein, a "purified nucleic acid" includes cDNAs, fragments of genomic nucleic acids, nucleic acids produced using the polymerase chain reaction (PCR), nucleic acids formed by restriction enzyme treatment of genomic nucleic acids, recombinant nucleic acids, and chemically synthesized nucleic acid molecules. A "recombinant" nucleic acid molecule includes a nucleic acid molecule made by an artificial combination of two otherwise separated segments of sequence, e.g., by chemical synthesis or by the manipulation of isolated segments of nucleic acids by genetic engineering techniques. As used herein, a "polypeptide" includes proteins, fragments of proteins, and peptides, whether isolated from natural sources, produced by recombinant techniques, or chemically synthesized. A polypeptide may have one or more modifications, such as a post-translational modification (e.g., glycosylation, phosphorylation, etc.) or any other modification (e.g., pegylation, etc.). The polypeptide may contain one or more non-naturally-occurring amino acids (e.g., such as an amino acid with a side chain modification).
[0111] In some embodiments, the nucleic acid sample can comprise cells or tissue, for example, cell lines. Exemplary cell types from which nucleic acids can be obtained using the methods described herein include, but are not limited to, the following: a blood cell such as a B lymphocyte, T lymphocyte, leukocyte, erythrocyte, macrophage, or neutrophil; a muscle cell such as a skeletal cell, smooth muscle cell or cardiac muscle cell; a germ cell, such as a sperm or egg; an epithelial cell; a connective tissue cell, such as an adipocyte, chondrocyte; fibroblast or osteoblast; a neuron; an astrocyte; a stromal cell; an organ specific cell, such as a kidney cell, pancreatic cell, liver cell, or a keratinocyte; a stem cell; or any cell that develops therefrom. A cell from which nucleic acids can be obtained can be a blood cell or a particular type of blood cell including, for example, a hematopoietic stem cell or a cell that arises from a hematopoietic stem cell such as a red blood cell, B lymphocyte, T lymphocyte, natural killer cell, neutrophil, basophil, eosinophil, monocyte, macrophage, or platelet. Generally, any type of stem cell can be used including, without limitation, an embryonic stem cell, adult stem cell, or pluripotent stem cell.
[0112] In some embodiments, a nucleic acid sample can be processed for RNA or DNA isolation, for example, RNA or DNA in a cell or tissue sample can be separated from other components of the nucleic acid sample. Cells can be harvested from a nucleic acid sample using standard techniques, for example, by centrifuging a cell sample and resuspending the pelleted cells, for example, in a buffered solution, for example, phosphate-buffered saline (PBS). In some embodiments, after centrifuging the cell suspension to obtain a cell pellet, the cells can be lysed to extract DNA. In some embodiments, the nucleic acid sample can be concentrated and/or purified to isolate DNA. All nucleic acid samples obtained from a subject, including those subjected to any sort of further processing, are considered to be obtained from the subject. In some embodiments, standard techniques and kits known in the art can be used to extract RNA or DNA from a nucleic acid sample, including, for example, phenol extraction, a QIAAMP.RTM. Tissue Kit (Qiagen, Chatsworth, Calif.), a WIZARD.RTM. Genomic DNA purification kit (Promega), or a Qiagen Autopure method using Puregene chemistry, which can enable purification of highly stable DNA well-suited for archiving.
[0113] In some embodiments, determining the identity of an allele or determining copy number can, but need not, include obtaining a nucleic acid sample comprising RNA and/or DNA from a subject, and/or assessing the identity, copy number, presence or absence of one or more genetic variations and their chromosomal locations within the genomic DNA (i.e. subject's genome) derived from the nucleic acid sample.
[0114] The individual or organization that performs the determination need not actually carry out the physical analysis of a nucleic acid sample from a subject. In some embodiments, the methods can include using information obtained by analysis of the nucleic acid sample by a third party. In some embodiments, the methods can include steps that occur at more than one site. For example, a nucleic acid sample can be obtained from a subject at a first site, such as at a health care provider or at the subject's home in the case of a self-testing kit. The nucleic acid sample can be analyzed at the same or a second site, for example, at a laboratory or other testing facility.
Nucleic Acids
[0115] The nucleic acids and polypeptides described herein can be used in methods and kits of the present disclosure. In some embodiments, aptamers that specifically bind the nucleic acids and polypeptides described herein can be used in methods and kits of the present disclosure. As used herein, a nucleic acid can comprise a deoxyribonucleotide (DNA) or ribonucleotide (RNA), whether singular or in polymers, naturally occurring or non-naturally occurring, double-stranded or single-stranded, coding, for example a translated gene, or non-coding, for example a regulatory region, or any fragments, derivatives, mimetics or complements thereof. In some embodiments, nucleic acids can comprise oligonucleotides, nucleotides, polynucleotides, nucleic acid sequences, genomic sequences, complementary DNA (cDNA), antisense nucleic acids, DNA regions, probes, primers, genes, regulatory regions, introns, exons, open-reading frames, binding sites, target nucleic acids and allele-specific nucleic acids.
[0116] A "probe," as used herein, includes a nucleic acid fragment for examining a nucleic acid in a specimen using the hybridization reaction based on the complementarity of nucleic acid.
[0117] A "hybrid" as used herein, includes a double strand formed between any one of the abovementioned nucleic acid, within the same type, or across different types, including DNA-DNA, DNA-RNA, RNA-RNA or the like.
[0118] "Isolated" nucleic acids, as used herein, are separated from nucleic acids that normally flank the gene or nucleotide sequence (as in genomic sequences) and/or has been completely or partially purified from other transcribed sequences (e.g., as in an RNA library). For example, isolated nucleic acids of the disclosure can be substantially isolated with respect to the complex cellular milieu in which it naturally occurs, or culture medium when produced by recombinant techniques, or chemical precursors or other chemicals when chemically synthesized. In some instances, the isolated material can form part of a composition, for example, a crude extract containing other substances, buffer system or reagent mix. In some embodiments, the material can be purified to essential homogeneity using methods known in the art, for example, by polyacrylamide gel electrophoresis (PAGE) or column chromatography (e.g., HPLC). With regard to genomic DNA (gDNA), the term "isolated" also can refer to nucleic acids that are separated from the chromosome with which the genomic DNA is naturally associated. For example, the isolated nucleic acid molecule can contain less than about 250 kb, 200 kb, 150 kb, 100 kb, 75 kb, 50 kb, 25 kb, 10 kb, 5 kb, 4 kb, 3 kb, 2 kb, 1 kb, 0.5 kb or 0.1 kb of the nucleotides that flank the nucleic acid molecule in the gDNA of the cell from which the nucleic acid molecule is derived.
[0119] Nucleic acids can be fused to other coding or regulatory sequences can be considered isolated. For example, recombinant DNA contained in a vector is included in the definition of "isolated" as used herein. In some embodiments, isolated nucleic acids can include recombinant DNA molecules in heterologous host cells or heterologous organisms, as well as partially or substantially purified DNA molecules in solution. Isolated nucleic acids also encompass in vivo and in vitro RNA transcripts of the DNA molecules of the present disclosure. An isolated nucleic acid molecule or nucleotide sequence can be synthesized chemically or by recombinant means. Such isolated nucleotide sequences can be useful, for example, in the manufacture of the encoded polypeptide, as probes for isolating homologous sequences (e.g., from other mammalian species), for gene mapping (e.g., by in situ hybridization with chromosomes), or for detecting expression of the gene, in tissue (e.g., human tissue), such as by Northern blot analysis or other hybridization techniques disclosed herein. The disclosure also pertains to nucleic acid sequences that hybridize under high stringency hybridization conditions, such as for selective hybridization, to a nucleotide sequence described herein Such nucleic acid sequences can be detected and/or isolated by allele- or sequence-specific hybridization (e.g., under high stringency conditions). Stringency conditions and methods for nucleic acid hybridizations are well known to the skilled person (see, e.g., Current Protocols in Molecular Biology, Ausubel, F. et al., John Wiley & Sons, (1998), and Kraus, M. and Aaronson, S., Methods Enzymol., 200:546-556 (1991), the entire teachings of which are incorporated by reference herein.
[0120] Calculations of "identity" or "percent identity" between two or more nucleotide or amino acid sequences can be determined by aligning the sequences for optimal comparison purposes (e.g., gaps can be introduced in the sequence of a first sequence). The nucleotides at corresponding positions are then compared, and the percent identity between the two sequences is a function of the number of identical positions shared by the sequences (i.e. % identity=# of identical positions/total # of positions.times.100). For example, a position in the first sequence is occupied by the same nucleotide as the corresponding position in the second sequence, then the molecules are identical at that position. The percent identity between the two sequences is a function of the number of identical positions shared by the sequences, taking into account the number of gaps, and the length of each gap, which need to be introduced for optimal alignment of the two sequences.
[0121] In some embodiments, the length of a sequence aligned for comparison purposes is at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95%, of the length of the reference sequence. The actual comparison of the two sequences can be accomplished by well-known methods, for example, using a mathematical algorithm. A non-limiting example of such a mathematical algorithm is described in Karlin, S. and Altschul, S., Proc. Natl. Acad. Sci. USA, 90-5873-5877 (1993). Such an algorithm is incorporated into the NBLAST and XBLAST programs (version 2.0), as described in Altschul, S. et al., Nucleic Acids Res., 25:3389-3402 (1997). When utilizing BLAST and Gapped BLAST programs, any relevant parameters of the respective programs (e.g., NBLAST) can be used. For example, parameters for sequence comparison can be set at score=100, word length=12, or can be varied (e.g., W=5 or W=20). Other examples include the algorithm of Myers and Miller, CABIOS (1989), ADVANCE, ADAM, BLAT, and FASTA. In some embodiments, the percent identity between two amino acid sequences can be accomplished using, for example, the GAP program in the GCG software package (Accelrys, Cambridge, UK).
[0122] "Probes" or "primers" can be oligonucleotides that hybridize in a base-specific manner to a complementary strand of a nucleic acid molecule. Probes can include primers, which can be a single-stranded oligonucleotide probe that can act as a point of initiation of template-directed DNA synthesis using methods including but not limited to, polymerase chain reaction (PCR) and ligase chain reaction (LCR) for amplification of a target sequence. Oligonucleotides, as described herein, can include segments or fragments of nucleic acid sequences, or their complements. In some embodiments, DNA segments can be between 5 and 10,000 contiguous bases, and can range from 5, 10, 12, 15, 20, or 25 nucleotides to 10, 15, 20, 25, 30, 40, 50, 100, 200, 500, 1000 or 10,000 nucleotides. In addition to DNA and RNA, probes and primers can include polypeptide nucleic acids (PNA), as described in Nielsen, P. et al., Science 254: 1497-1500 (1991). A probe or primer can comprise a region of nucleotide sequence that hybridizes to at least about 15, typically about 20-25, and in certain embodiments about 40, 50, 60 or 75, consecutive nucleotides of a nucleic acid molecule.
[0123] The present disclosure also provides isolated nucleic acids, for example, probes or primers, that contain a fragment or portion that can selectively hybridize to a nucleic acid that comprises, or consists of, a nucleotide sequence, wherein the nucleotide sequence can comprise at least one polymorphism or polymorphic allele contained in the genetic variations described herein or the wild-type nucleotide that is located at the same position, or the complements thereof. In some embodiments, the probe or primer can be at least 70% identical, at least 80% identical, at least 85% identical, at least 90% identical, or at least 95% identical, to the contiguous nucleotide sequence or to the complement of the contiguous nucleotide sequence.
[0124] In some embodiments, a nucleic acid probe can be an oligonucleotide capable of hybridizing with a complementary region of a gene associated with a condition (e.g., LHON) containing a genetic variation described herein. The nucleic acid fragments of the disclosure can be used as probes or primers in assays such as those described herein.
[0125] The nucleic acids of the disclosure, such as those described above, can be identified and isolated using standard molecular biology techniques well known to the skilled person. In some embodiments, DNA can be amplified and/or can be labeled (e.g., radiolabeled, fluorescently labeled) and used as a probe for screening, for example, a cDNA library derived from an organism. cDNA can be derived from mRNA and can be contained in a suitable vector. For example, corresponding clones can be isolated, DNA obtained fallowing in vivo excision, and the cloned insert can be sequenced in either or both orientations by art-recognized methods to identify the correct reading frame encoding a polypeptide of the appropriate molecular weight. Using these or similar methods, the polypeptide and the DNA encoding the polypeptide can be isolated, sequenced and further characterized.
[0126] In some embodiments, nucleic acid can comprise one or more polymorphisms, variations, or mutations, for example, single nucleotide polymorphisms (SNPs), single nucleotide variations (SNVs), copy number variations (CNVs), for example, insertions, deletions, inversions, and translocations. In some embodiments, nucleic acids can comprise analogs, for example, phosphorothioates, phosphoramidates, methyl phosphonate, chiralmethyl phosphonates, 2-0-methyl ribonucleotides, or modified nucleic acids, for example, modified backbone residues or linkages, or nucleic acids combined with carbohydrates, lipids, polypeptide or other materials, or peptide nucleic acids (PNAs), for example, chromatin, ribosomes, and transcriptosomes. In some embodiments nucleic acids can comprise nucleic acids in various structures, for example, A DNA, B DNA, Z-form DNA, siRNA, tRNA, and ribozymes. In some embodiments, the nucleic acid may be naturally or non-naturally polymorphic, for example, having one or more sequence differences, for example, additions, deletions and/or substitutions, as compared to a reference sequence. In some embodiments, a reference sequence can be based on publicly available information, for example, the U.C. Santa Cruz Human Genome Browser Gateway (genome.ucsc.edu/cgi-bin/hgGateway) or the NCBI website (www.ncbi.nlm.nih.gov). In some embodiments, a reference sequence can be determined by a practitioner of the present disclosure using methods well known in the art, for example, by sequencing a reference nucleic acid.
[0127] In some embodiments, a probe can hybridize to an allele, SNP, SNV, or CNV as described herein. In some embodiments, the probe can bind to another marker sequence associated with LHON as described herein.
[0128] One of skill in the art would know how to design a probe so that sequence specific hybridization can occur only if a particular allele is present in a genomic sequence from a test nucleic acid sample. The disclosure can also be reduced to practice using any convenient genotyping method, including commercially available technologies and methods for genotyping particular genetic variations.
[0129] Control probes can also be used, for example, a probe that binds a less variable sequence, for example, a repetitive DNA associated with a centromere of a chromosome, can be used as a control. In some embodiments, probes can be obtained from commercial sources. In some embodiments, probes can be synthesized, for example, chemically or in vitro, or made from chromosomal or genomic DNA through standard techniques. In some embodiments sources of DNA that can be used include genomic DNA, cloned DNA sequences, somatic cell hybrids that contain one, or a part of one, human chromosome along with the normal chromosome complement of the host, and chromosomes purified by flow cytometry or microdissection. The region of interest can be isolated through cloning, or by site-specific amplification using PCR.
[0130] One or more nucleic acids for example, a probe or primer, can also be labeled, for example, by direct labeling, to comprise a detectable label. A detectable label can comprise any label capable of detection by a physical, chemical, or a biological process for example, a radioactive label, such as 32P or 3H, a fluorescent label, such as FITC, a chromophore label, an affinity-ligand label, an enzyme label, such as alkaline phosphatase, horseradish peroxidase, or 12 galactosidase, an enzyme cofactor label, a hapten conjugate label, such as digoxigenin or dinitrophenyl, a Raman signal generating label, a magnetic label, a spin label, an epitope label, such as the FLAG or HA epitope, a luminescent label, a heavy atom label, a nanoparticle label, an electrochemical label, a light scattering label, a spherical shell label, semiconductor nanocrystal label, such as quantum dots (described in U.S. Pat. No. 6,207,392), and probes labeled with any other signal generating label known to those of skill in the art, wherein a label can allow the probe to be visualized with or without a secondary detection molecule. A nucleotide can be directly incorporated into a probe with standard techniques, for example, nick translation, random priming, and PCR labeling. A "signal," as used herein, include a signal suitably detectable and measurable by appropriate means, including fluorescence, radioactivity, chemiluminescence, and the like.
[0131] Non-limiting examples of label moieties useful for detection include, without limitation, suitable enzymes such as horseradish peroxidase, alkaline phosphatase, beta-galactosidase, or acetylcholinesterase; members of a binding pair that are capable of forming complexes such as streptavidin/biotin, avidin/biotin or an antigen/antibody complex including, for example, rabbit IgG and anti-rabbit IgG, fluorophores such as umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, tetramethyl rhodamine, eosin, green fluorescent protein, erythrosin, coumarin, methyl coumarin, pyrene, malachite green, stilbene, lucifer yellow, Cascade Blue, Texas Red, dichlorotriazinylamine fluorescein, dansyl chloride, phycoerythrin, fluorescent lanthanide complexes such as those including Europium and Terbium, cyanine dye family members, such as Cy3 and Cy5, molecular beacons and fluorescent derivatives thereof, as well as others known in the art as described, for example, in Principles of Fluorescence Spectroscopy, Joseph R. Lakowicz (Editor), Plenum Pub Corp, 2nd edition (July 1999) and the 6th Edition of the Molecular Probes Handbook by Richard P. Hoagland; a luminescent material such as luminol, light scattering or plasmon resonant materials such as gold or silver particles or quantum dots; or radioactive material include 14C, 1231, 1241, 1251, Tc99m, 32P, 33P, 35S or 3H.
[0132] Other labels can also be used in the methods of the present disclosure, for example, backbone labels. Backbone labels comprise nucleic acid stains that bind nucleic acids in a sequence independent manner. Non-limiting examples include intercalating dyes such as phenanthridines and acridines (e.g., ethidium bromide, propidium iodide, hexidium iodide, dihydroethidium, ethidium homodimer-1 and -2, ethidium monoazide, and ACMA); some minor grove binders such as indoles and imidazoles (e.g., Hoechst 33258, Hoechst 33342, Hoechst 34580 and DAPI); and miscellaneous nucleic acid stains such as acridine orange (also capable of intercalating), 7-AAD, actinomycin D, LDS751, and hydroxystilbamidine. All of the aforementioned nucleic acid stains are commercially available from suppliers such as Molecular Probes, Inc. Still other examples of nucleic acid stains include the following dyes from Molecular Probes: cyanine dyes such as SYTOX Blue, SYTOX Green, SYTOX Orange, POPO-1, POPO-3, YOYO-1, YOYO-3, TOTO-1, TOTO-3, JOJO-1, LOLO-1, BOBO-1, BOBO-3, PO-PRO-1, PO-PRO-3, BO-PRO-1, BO-PRO-3, TO-PRO-1, TO-PRO-3, TO-PRO-5, JO-PRO-1, LO-PRO-1, YO-PRO-1, YO-PRO-3, PicoGreen, OliGreen, RiboGreen, SYBR Gold, SYBR Green I, SYBR Green 11, SYBR DX, SYTO-40, -41, -42, -43, -44, -45 (blue), SYTO-13, -16, -24, -21, -23, -12, -11, -20, -22, -15, -14, -25 (green), SYTO-81, -80, -82, -83, -84, -85 (orange), SYTO-64, -17, -59, -61, -62, -60, -63 (red).
[0133] In some embodiments, fluorophores of different colors can be chosen, for example, 7-amino-4-methylcoumarin-3-acetic acid (AMCA), 5-(and-6)-carboxy-X-rhodamine, lissamine rhodamine B, 5-(and-6)-carboxyfluorescein, fluorescein-5-isothiocyanate (FITC), 7-diethylaminocoumarin-3-carboxylic acid, tetramethylrhodamine-5-(and-6)-isothiocyanate, 5-(and-6)-carboxytetramethylrhodamine, 7-hydroxycoumarin-3-carboxylic acid, 6-[fluorescein 5-(and-6)-carboxamido]hexanoic acid, N-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a diaza-3-indacenepropionic acid, eosin-5-isothiocyanate, erythrosin-5-isothiocyanate, TRITC, rhodamine, tetramethylrhodamine, R-phycoerythrin, Cy-3, Cy-5, Cy-7, Texas Red, Phar-Red, allophycocyanin (APC), and CASCADETM blue acetylazide, such that each probe in or not in a set can be distinctly visualized. In some embodiments, fluorescently labeled probes can be viewed with a fluorescence microscope and an appropriate filter for each fluorophore, or by using dual or triple band-pass filter sets to observe multiple fluorophores. In some embodiments, techniques such as flow cytometry can be used to examine the hybridization pattern of the probes.
[0134] In other embodiments, the probes can be indirectly labeled, for example, with biotin or digoxygenin, or labeled with radioactive isotopes such as 32P and/or 3H. As a non-limiting example, a probe indirectly labeled with biotin can be detected by avidin conjugated to a detectable marker. For example, avidin can be conjugated to an enzymatic marker such as alkaline phosphatase or horseradish peroxidase. In some embodiments, enzymatic markers can be detected using colorimetric reactions using a substrate and/or a catalyst for the enzyme. In some embodiments, catalysts for alkaline phosphatase can be used, for example, 5-bromo-4-chloro-3-indolylphosphate and nitro blue tetrazolium. In some embodiments, a catalyst can be used for horseradish peroxidase, for example, diaminobenzoate.
Formulations, Routes of Administration, and Effective Doses
[0135] Yet another aspect of the present disclosure relates to formulations, routes of administration and effective doses for pharmaceutical compositions comprising an agent or combination of agents of the instant disclosure. Such pharmaceutical compositions can be used to treat a condition (e.g., LHON) as described above.
[0136] Compounds of the disclosure can be administered as pharmaceutical formulations including those suitable for oral (including buccal and sub-lingual), rectal, nasal, topical, transdermal patch, pulmonary, vaginal, suppository, or parenteral (including intraocular, intravitreal, intramuscular, intraarterial, intrathecal, intradermal, intraperitoneal, subcutaneous and intravenous) administration or in a form suitable for administration by aerosolization, inhalation or insufflation. General information on drug delivery systems can be found in Ansel et al., Pharmaceutical Dosage Forms and Drug Delivery Systems (Lippencott Williams & Wilkins, Baltimore Md. (1999).
[0137] In various embodiments, the pharmaceutical composition includes carriers and excipients (including but not limited to buffers, carbohydrates, mannitol, polypeptides, amino acids, antioxidants, bacteriostats, chelating agents, suspending agents, thickening agents and/or preservatives), water, oils including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil and the like, saline solutions, aqueous dextrose and glycerol solutions, flavoring agents, coloring agents, detackifiers and other acceptable additives, adjuvants, or binders, other pharmaceutically acceptable auxiliary substances to approximate physiological conditions, such as pH buffering agents, tonicity adjusting agents, emulsifying agents, wetting agents and the like. Examples of excipients include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol and the like. In some embodiments, the pharmaceutical preparation is substantially free of preservatives. In other embodiments, the pharmaceutical preparation can contain at least one preservative. General methodology on pharmaceutical dosage forms is found in Ansel et al., Pharmaceutical Dosage Forms and Drug Delivery Systems (Lippencott, Williams, & Wilkins, Baltimore Md. (1999)). It can be recognized that, while any suitable carrier known to those of ordinary skill in the art can be employed to administer the compositions of this disclosure, the type of carrier can vary depending on the mode of administration.
[0138] Compounds can also be encapsulated within liposomes using well-known technology. Biodegradable microspheres can also be employed as carriers for the pharmaceutical compositions of this disclosure. Suitable biodegradable microspheres are disclosed, for example, in U.S. Pat. Nos. 4,897,268, 5,075,109, 5,928,647, 5,811,128, 5,820,883, 5,853,763, 5,814,344 and 5,942,252.
[0139] The compound can be administered in liposomes or microspheres (or microparticles). Methods for preparing liposomes and microspheres for administration to a subject are well known to those of skill in the art. U.S. Pat. No. 4,789,734, the contents of which are hereby incorporated by reference, describes methods for encapsulating biological materials in liposomes. Essentially, the material is dissolved in an aqueous solution, the appropriate phospholipids and lipids added, and along with surfactants if required, and the material dialyzed or sonicated, as necessary. A review of known methods is provided by G. Gregoriadis, Chapter 14, "Liposomes," Drug Carriers in Biology and Medicine, pp. 2.sup.87-341 (Academic Press, 1979).
[0140] Microspheres formed of polymers or polypeptides are well known to those skilled in the art, and can be tailored for passage through the gastrointestinal tract directly into the blood stream. Alternatively, the compound can be incorporated and the microspheres, or composite of microspheres, implanted for slow release over a period of time ranging from days to months. See, for example, U.S. Pat. Nos. 4,906,474, 4,925,673 and 3,625,214, and Jein, TIPS 19:155-157 (1998), the contents of which are hereby incorporated by reference.
[0141] The concentration of drug can be adjusted, the pH of the solution buffered and the isotonicity adjusted to be compatible with intraocular or intravitreal injection.
[0142] The compounds of the disclosure can be formulated as a sterile solution or suspension, in suitable vehicles. The pharmaceutical compositions can be sterilized by conventional, well-known sterilization techniques, or can be sterile filtered. The resulting aqueous solutions can be packaged for use as is, or lyophilized, the lyophilized preparation being combined with a sterile solution prior to administration. Suitable formulations and additional carriers are described in Remington "The Science and Practice of Pharmacy" (20th Ed., Lippincott Williams & Wilkins, Baltimore Md.), the teachings of which are incorporated by reference in their entirety herein.
[0143] The agents or their pharmaceutically acceptable salts can be provided alone or in combination with one or more other agents or with one or more other forms. For example, a formulation can comprise one or more agents in particular proportions, depending on the relative potencies of each agent and the intended indication. For example, in compositions for targeting two different host targets, and where potencies are similar, about a 1:1 ratio of agents can be used. The two forms can be formulated together, in the same dosage unit e.g., in one cream, suppository, tablet, capsule, aerosol spray, or packet of powder to be dissolved in a beverage; or each form can be formulated in a separate unit, e.g., two creams, two suppositories, two tablets, two capsules, a tablet and a liquid for dissolving the tablet, two aerosol sprays, or a packet of powder and a liquid for dissolving the powder, etc.
[0144] The term "pharmaceutically acceptable salt" means those salts which retain the biological effectiveness and properties of the agents used in the present disclosure, and which are not biologically or otherwise undesirable.
[0145] Typical salts are those of the inorganic ions, such as, for example, sodium, potassium, calcium, magnesium ions, and the like. Such salts include salts with inorganic or organic acids, such as hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, methanesulfonic acid, p toluenesulfonic acid, acetic acid, fumaric acid, succinic acid, lactic acid, mandelic acid, malic acid, citric acid, tartaric acid or maleic acid. In addition, if the agent(s) contain a carboxyl group or other acidic group, it can be converted into a pharmaceutically acceptable addition salt with inorganic or organic bases. Examples of suitable bases include sodium hydroxide, potassium hydroxide, ammonia, cyclohexylamine, dicyclohexyl-amine, ethanolamine, diethanolamine, triethanolamine, and the like.
[0146] A pharmaceutically acceptable ester or amide refers to those which retain biological effectiveness and properties of the agents used in the present disclosure, and which are not biologically or otherwise undesirable. Typical esters include ethyl, methyl, isobutyl, ethylene glycol, and the like. Typical amides include unsubstituted amides, alkyl amides, dialkyl amides, and the like.
[0147] In some embodiments, an agent can be administered in combination with one or more other compounds, forms, and/or agents, e.g., as described above. Pharmaceutical compositions with one or more other active agents can be formulated to comprise certain molar ratios. For example, molar ratios of about 99:1 to about 1:99 of a first active agent to the other active agent can be used. In some subset of the embodiments, the range of molar ratios of a first active agent: other active agents are selected from about 80:20 to about 20:80; about 75:25 to about 25:75, about 70:30 to about 30:70, about 66:33 to about 33:66, about 60:40 to about 40:60; about 50:50; and about 90:10 to about 10:90. The molar ratio of a first active: other active agents can be about 1:9, and in some embodiments can be about 1:1. The two agents, forms and/or compounds can be formulated together, in the same dosage unit e.g., in one cream, suppository, tablet, capsule, or packet of powder to be dissolved in a beverage; or each agent, form, and/or compound can be formulated in separate units, e.g., two creams, suppositories, tablets, two capsules, a tablet and a liquid for dissolving the tablet, an aerosol spray a packet of powder and a liquid for dissolving the powder, etc.
[0148] If necessary or desirable, the agents and/or combinations of agents can be administered with still other agents. The choice of agents that can be co-administered with the agents and/or combinations of agents of the instant disclosure can depend, at least in part, on the condition being treated.
[0149] The agent(s) (or pharmaceutically acceptable salts, esters or amides thereof) can be administered per se or in the form of a pharmaceutical composition wherein the active agent(s) is in an admixture or mixture with one or more pharmaceutically acceptable carriers. A pharmaceutical composition, as used herein, can be any composition prepared for administration to a subject. Pharmaceutical compositions for use in accordance with the present disclosure can be formulated in conventional manner using one or more physiologically acceptable carriers, comprising excipients, diluents, and/or auxiliaries, e.g., which facilitate processing of the active agents into preparations that can be administered. Proper formulation can depend at least in part upon the route of administration chosen. The agent(s) useful in the present disclosure, or pharmaceutically acceptable salts, esters, or amides thereof, can be delivered to a subject using a number of routes or modes of administration, including oral, buccal, topical, rectal, transdermal, transmucosal, subcutaneous, intravenous, intraocular, intravitreal, and intramuscular applications, as well as by inhalation.
[0150] In some embodiments, oils or non-aqueous solvents can be used to bring the agents into solution, due to, for example, the presence of large lipophilic moieties. Alternatively, emulsions, suspensions, or other preparations, for example, liposomal preparations, can be used. With respect to liposomal preparations, any known methods for preparing liposomes for treatment of a condition can be used. See, for example, Bangham et al., J. Mol. Biol. 23: 238-252 (1965) and Szoka et al., Proc. Natl Acad. Sci. USA 75: 4194-4198 (1978), incorporated herein by reference. Ligands can also be attached to the liposomes to direct these compositions to particular sites of action. Agents of this disclosure can also be integrated into foodstuffs, e.g., cream cheese, butter, salad dressing, or ice cream to facilitate solubilization, administration, and/or compliance in certain subject populations.
[0151] The compounds of the disclosure can be formulated for parenteral administration (e.g., by injection, for example, intraocular or intravitreal injection) and can be presented in unit dose form in ampoules, pre-filled syringes, small volume infusion or in multi-dose containers with an added preservative. The compositions can take such forms as suspensions, solutions, or emulsions in oily or aqueous vehicles, for example, solutions in aqueous polyethylene glycol.
[0152] For injectable formulations, the vehicle can be chosen from those known in art to be suitable, including aqueous solutions or oil suspensions, or emulsions, with sesame oil, corn oil, cottonseed oil, or peanut oil, as well as elixirs, mannitol, dextrose, or a sterile aqueous solution, and similar pharmaceutical vehicles. The formulation can also comprise polymer compositions which are biocompatible, biodegradable, such as poly(lactic-co-glycolic)acid. These materials can be made into micro or nanospheres, loaded with drug and further coated or derivatized to provide superior sustained release performance. Vehicles suitable for periocular or intraocular injection include, for example, suspensions of therapeutic agent in injection grade water, liposomes and vehicles suitable for lipophilic substances. Other vehicles for periocular or intraocular injection are well known in the art.
[0153] In some embodiments, the composition is formulated in accordance with routine procedures as a pharmaceutical composition adapted for intravenous administration to human beings. Typically, compositions for intravenous administration are solutions in sterile isotonic aqueous buffer. Where necessary, the composition can also include a solubilizing agent and a local anesthetic such as lidocaine to ease pain at the site of the injection. Generally, the ingredients are supplied either separately or mixed together in unit dosage form, for example, as a dry lyophilized powder or water free concentrate in a hermetically sealed container such as an ampoule or sachette indicating the quantity of active agent. Where the composition is to be administered by infusion, it can be dispensed with an infusion bottle containing sterile pharmaceutical grade water or saline. Where the composition is administered by injection, an ampoule of sterile water for injection or saline can be provided so that the ingredients can be mixed prior to administration.
[0154] When administration is by injection, the active compound can be formulated in aqueous solutions, specifically in physiologically compatible buffers such as Hanks solution, Ringer's solution, or physiological saline buffer. The solution can contain formulatory agents such as suspending, stabilizing and/or dispersing agents. Alternatively, the active compound can be in powder form for constitution with a suitable vehicle, e.g., sterile pyrogen-free water, before use. In some embodiments, the pharmaceutical composition does not comprise an adjuvant or any other substance added to enhance the immune response stimulated by the peptide. In some embodiments, the pharmaceutical composition comprises a substance that inhibits an immune response to the peptide. Methods of formulation are known in the art, for example, as disclosed in Remington's Pharmaceutical Sciences, latest edition, Mack Publishing Co., Easton P.
[0155] In some embodiments, eye disorders can be effectively treated with ophthalmic solutions, suspensions, ointments or inserts comprising an agent or combination of agents of the present disclosure. Eye drops can be prepared by dissolving the active ingredient in a sterile aqueous solution such as physiological saline, buffering solution, etc., or by combining powder compositions to be dissolved before use. Other vehicles can be chosen, as is known in the art, including but not limited to: balance salt solution, saline solution, water soluble polyethers such as polyethyene glycol, polyvinyls, such as polyvinyl alcohol and povidone, cellulose derivatives such as methylcellulose and hydroxypropyl methylcellulose, petroleum derivatives such as mineral oil and white petrolatum, animal fats such as lanolin, polymers of acrylic acid such as carboxypolymethylene gel, vegetable fats such as peanut oil and polysaccharides such as dextrans, and glycosaminoglycans such as sodium hyaluronate. If desired, additives ordinarily used in the eye drops can be added. Such additives include isotonizing agents (e.g., sodium chloride, etc.), buffer agent (e.g., boric acid, sodium monohydrogen phosphate, sodium dihydrogen phosphate, etc.), preservatives (e.g., benzalkonium chloride, benzethonium chloride, chlorobutanol, etc.), thickeners (e.g., saccharide such as lactose, mannitol, maltose, etc.; e.g., hyaluronic acid or its salt such as sodium hyaluronate, potassium hyaluronate, etc.; e.g., mucopolysaccharide such as chondroitin sulfate, etc.; e.g., sodium polyacrylate, carboxyvinyl polymer, crosslinked polyacrylate, polyvinyl alcohol, polyvinyl pyrrolidone, methyl cellulose, hydroxy propyl methylcellulose, hydroxyethyl cellulose, carboxymethyl cellulose, hydroxy propyl cellulose or other agents known to those skilled in the art).
[0156] The solubility of the components of the present compositions can be enhanced by a surfactant or other appropriate co-solvent in the composition. Such cosolvents include polysorbate 20, 60, and 80, Pluronic F68, F-84 and P-103, cyclodextrin, or other agents known to those skilled in the art. Such co-solvents can be employed at a level of from about 0.01% to 2% by weight.
[0157] The compositions of the disclosure can be packaged in multidose form. Preservatives can be preferred to prevent microbial contamination during use. Suitable preservatives include: benzalkonium chloride, thimerosal, chlorobutanol, methyl paraben, propyl paraben, phenylethyl alcohol, edetate disodium, sorbic acid, Onamer M, or other agents known to those skilled in the art. In the prior art ophthalmic products, such preservatives can be employed at a level of from 0.004% to 0.02%. In the compositions of the present application the preservative, preferably benzalkonium chloride, can be employed at a level of from 0.001% to less than 0.01%, e.g., from 0.001% to 0.008%, preferably about 0.005% by weight. It has been found that a concentration of benzalkonium chloride of 0.005% can be sufficient to preserve the compositions of the present disclosure from microbial attack.
[0158] In some embodiments, the agents of the present disclosure are delivered in soluble rather than suspension form, which allows for more rapid and quantitative absorption to the sites of action. In general, formulations such as jellies, creams, lotions, suppositories and ointments can provide an area with more extended exposure to the agents of the present disclosure, while formulations in solution, e.g., sprays, provide more immediate, short-term exposure.
[0159] It is envisioned additionally, that the compounds of the disclosure can be attached releasably to biocompatible polymers for use in sustained release formulations on, in or attached to inserts for topical, intraocular, periocular, or systemic administration. The controlled release from a biocompatible polymer can be utilized with a water soluble polymer to form an instillable formulation, as well. The controlled release from a biocompatible polymer, such as for example, PLGA microspheres or nanospheres, can be utilized in a formulation suitable for intra ocular implantation or injection for sustained release administration, as well any suitable biodegradable and biocompatible polymer can be used.
FURTHER NUMBERED EMBODIMENTS
[0160] Further numbered embodiments of the disclosure are provided here as follows:
[0161] Embodiment 1. A recombinant nucleic acid, comprising:
[0162] a mitochondrial targeting sequence;
[0163] a mitochondrial protein coding sequence comprising a sequence that is at least 99% identical to SEQ ID NO: 11 or 12; and
[0164] a 3'UTR nucleic acid sequence.
[0165] Embodiment 2. The recombinant nucleic acid of Embodiment 1, wherein said mitochondrial targeting sequence encodes a polypeptide comprising a peptide sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 129-159.
[0166] Embodiment 3. The recombinant nucleic acid of Embodiment 1, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 2.
[0167] Embodiment 4. The recombinant nucleic acid of Embodiment 1, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 3.
[0168] Embodiment 5. The recombinant nucleic acid of Embodiment 1, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 4.
[0169] Embodiment 6. The recombinant nucleic acid of Embodiment 1, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 5.
[0170] Embodiment 7. The recombinant nucleic acid of Embodiment 1, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 1.
[0171] Embodiment 8. The recombinant nucleic acid of Embodiment 1, wherein said mitochondrial protein coding sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 12.
[0172] Embodiment 8.1. The recombinant nucleic acid of Embodiment 1, wherein said mitochondrial protein coding sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 11.
[0173] Embodiment 9. The recombinant nucleic acid of any one of Embodiments 1-8 and 8.1, wherein said 3'UTR nucleic acid sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 111-125.
[0174] Embodiment 10. The recombinant nucleic acid of any one of Embodiments 1-8 and 8.1, wherein said 3'UTR nucleic acid sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 13 or SEQ ID NO: 14.
[0175] Embodiment 11. The recombinant nucleic acid of Embodiment 1, wherein said recombinant nucleic acid comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 25-28, 39-42, 53-56, 67-70, and 81-84.
[0176] Embodiment 12. A recombinant nucleic acid, comprising:
[0177] a mitochondrial targeting sequence;
[0178] a mitochondrial protein coding sequence comprising a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to SEQ ID NO: 11 or 12; and
[0179] a 3'UTR nucleic acid sequence.
[0180] Embodiment 13. The recombinant nucleic acid of Embodiment 12, wherein said mitochondrial targeting sequence comprises a sequence encodes a polypeptide selected from the group consisting of hsCOX10, hsCOX8, scRPM2, IcSirt5, tbNDUS7, ncQCR2, hsATP5G2, hsLACTB, spilv1, gmCOX2, crATP6, hsOPA1, hsSDHD, hsADCK3, osP0644B06.24-2, Neurospora crassa ATP9 (ncATP9), hsGHITM, hsNDUFAB1, hsATP5G3, crATP6_hsADCK3, ncATP9_ncATP9, zmLOC100282174, ncATP9_zmLOC100282174_spilv1_ncATP9, zmLOC100282174_hsADCK3_crATP6_hsATP5G3, zmLOC100282174_hsADCK3_hsATP5G3, ncATP9_zmLOC100282174, hsADCK3_zmLOC100282174_crATP6_hsATP5G3, crATP6_hsADCK3_zmLOC100282174_hsATP5G3, hsADCK3_zmLOC100282174, hsADCK3_zmLOC100282174_crATP6, ncATP9_zmLOC100282174_spilv1_GNFP_ncATP9, and ncATP9_zmLOC100282174_spilv1_IcSirt5_osP0644 B06.24-2_hsATP5G2_ncATP9.
[0181] Embodiment 14. The recombinant nucleic acid of Embodiment 12 or 13, wherein said mitochondrial targeting sequence encodes a polypeptide comprising a peptide sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 129-159.
[0182] Embodiment 15. The recombinant nucleic acid of any one of Embodiments 12-14, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 2 or 3.
[0183] Embodiment 16. The recombinant nucleic acid of any one of Embodiments 12-14, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 4.
[0184] Embodiment 17. The recombinant nucleic acid of any one of Embodiments 12-14, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 5.
[0185] Embodiment 18. The recombinant nucleic acid of any one of Embodiments 12-14, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 1.
[0186] Embodiment 19. The recombinant nucleic acid of any one of Embodiments 12-18, wherein said 3'UTR nucleic acid sequence is located at 3' of said mitochondrial targeting sequence.
[0187] Embodiment 20. The recombinant nucleic acid of any one of Embodiments 12-19, wherein said 3'UTR nucleic acid sequence comprises a sequence selected from the group consisting of hsACO2, hsATP5B, hsAK2, hsALDH2, hsCOX10, hsUQCRFS1, hsNDUFV1, hsNDUFV2, hsSOD2, hsCOX6c, hsIRP1, hsMRPS12, hsATP5J2, rnSOD2, and hsOXA1L.
[0188] Embodiment 21. The recombinant nucleic acid of any one of Embodiments 12-20, wherein said 3'UTR nucleic acid sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 111-125.
[0189] Embodiment 22. The recombinant nucleic acid of any one of Embodiments 12-21, wherein said 3'UTR nucleic acid sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 13 or SEQ ID NO: 14.
[0190] Embodiment 23. The recombinant nucleic acid of any one of Embodiments 12-22, wherein said mitochondrial targeting sequence is located at 5' of said 3'UTR nucleic acid sequence.
[0191] Embodiment 24. The recombinant nucleic acid of any one of Embodiments 12-22, wherein said mitochondrial targeting sequence is located at 3' of said mitochondrial targeting sequence.
[0192] Embodiment 25. The recombinant nucleic acid of any one of Embodiments 12-24, wherein said recombinant nucleic acid comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 25-28, 39-42, 53-56, 67-70, and 81-84.
[0193] Embodiment 26. The recombinant nucleic acid of any one of Embodiments 12-25, wherein said mitochondrial protein coding sequence encodes a mitochondrial protein comprising or consisting of a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 162.
[0194] Embodiment 27. A recombinant nucleic acid, comprising a mitochondrial protein coding sequence, wherein said mitochondrial protein coding sequence encodes a polypeptide comprising a mitochondrial protein, wherein said mitochondrial protein coding sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to SEQ ID NO: 11 or 12.
[0195] Embodiment 28. The recombinant nucleic acid of Embodiment 27, further comprising a mitochondrial targeting sequence.
[0196] Embodiment 29. The recombinant nucleic acid of Embodiment 27 or 28, wherein said mitochondrial targeting sequence comprises a sequence encodes a polypeptide selected from the group consisting of hsCOX10, hsCOX8, scRPM2, IcSirt5, tbNDUS7, ncQCR2, hsATP5G2, hsLACTB, spilv1, gmCOX2, crATP6, hsOPA1, hsSDHD, hsADCK3, osP0644B06.24-2, Neurospora crassa ATP9 (ncATP9), hsGHITM, hsNDUFAB1, hsATP5G3, crATP6_hsADCK3, ncATP9_ncATP9, zmLOC100282174, ncATP9_zmLOC100282174_spilv1_ncATP9, zmLOC100282174_hsADCK3_crATP6_hsATP5G3, zmLOC100282174_hsADCK3_hsATP5G3, ncATP9_zmLOC100282174, hsADCK3_zmLOC100282174_crATP6_hsATP5G3, crATP6_hsADCK3_zmLOC100282174_hsATP5G3, hsADCK3_zmLOC100282174, hsADCK3_zmLOC100282174_crATP6, ncATP9_zmLOC100282174_spilv1_GNFP_ncATP9, and ncATP9_zmLOC100282174_spilv1_IcSirt5_osP0644 B06.24-2_hsATP5G2_ncATP9.
[0197] Embodiment 30. The recombinant nucleic acid of any one of Embodiments 27-29, wherein said mitochondrial targeting sequence encodes a polypeptide comprising a peptide sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 129-159.
[0198] Embodiment 31. The recombinant nucleic acid of any one of Embodiments 27-30, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 2.
[0199] Embodiment 32. The recombinant nucleic acid of any one of Embodiments 27-31, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 3.
[0200] Embodiment 33. The recombinant nucleic acid of any one of Embodiments 27-32, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 4.
[0201] Embodiment 34. The recombinant nucleic acid of any one of Embodiments 27-33, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 5.
[0202] Embodiment 35. The recombinant nucleic acid of any one of Embodiments 27-34, wherein said mitochondrial targeting sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 1.
[0203] Embodiment 36. The recombinant nucleic acid of any one of Embodiments 27-35, further comprising a 3'UTR nucleic acid sequence.
[0204] Embodiment 37. The recombinant nucleic acid of Embodiment 36, wherein said 3'UTR nucleic acid sequence is located at 3' of said mitochondrial targeting sequence.
[0205] Embodiment 38. The recombinant nucleic acid of Embodiment 36 or 37, wherein said 3'UTR nucleic acid sequence comprises a sequence selected from the group consisting of hsACO2, hsATP5B, hsAK2, hsALDH2, hsCOX10, hsUQCRFS1, hsNDUFV1, hsNDUFV2, hsSOD2, hsCOX6c, hsIRP1, hsMRPS12, hsATP5J2, rnSOD2, and hsOXA1L.
[0206] Embodiment 39. The recombinant nucleic acid of any one of Embodiments 36-38, wherein said 3'UTR nucleic acid sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 111-125.
[0207] Embodiment 40. The recombinant nucleic acid of any one of Embodiments 36-39, wherein said 3'UTR nucleic acid sequence comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence as set forth in SEQ ID NO: 13 or SEQ ID NO: 14.
[0208] Embodiment 41. The recombinant nucleic acid of any one of Embodiments 36-40, wherein said mitochondrial targeting sequence is located at 5' of said 3'UTR nucleic acid sequence.
[0209] Embodiment 42. The recombinant nucleic acid of any one of Embodiments 36-41, wherein said mitochondrial targeting sequence is located at 3' of said mitochondrial targeting sequence.
[0210] Embodiment 43. The recombinant nucleic acid of any one of Embodiments 36-42, wherein said recombinant nucleic acid comprises a sequence that is at least 90%, at least 95%, at least 97%, at least 99%, or 100% identical to a sequence selected from the group consisting of SEQ ID NO: 25-28, 39-42, 53-56, 67-70, and 81-84.
[0211] Embodiment 44. A viral vector comprising said recombinant nucleic acid of any one of Embodiments 1-43.
[0212] Embodiment 45. The viral vector of Embodiment 44, wherein said viral vector is an adeno-associated virus (AAV) vector.
[0213] Embodiment 46. The viral vector of Embodiment 45, wherein said AAV vector is selected from the group consisting of AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, AAV12, AAV13, AAV14, AAV15, and AAV16 vectors.
[0214] Embodiment 47. The viral vector of Embodiment 45 or 46, wherein said AAV vector is a recombinant AAV (rAAV) vector.
[0215] Embodiment 48. The viral vector of Embodiment 47, wherein said rAAV vector is rAAV2 vector.
[0216] Embodiment 49. A pharmaceutical composition, comprising an adeno-associated virus (AAV) comprising said recombinant nucleic acid of any one of Embodiments 1-43.
[0217] Embodiment 50. The pharmaceutical composition of Embodiment 49, further comprising a pharmaceutically acceptable excipient thereof.
[0218] Embodiment 51. A pharmaceutical composition, comprising said viral vector of any one of Embodiments 44-48, and a pharmaceutically acceptable excipient thereof.
[0219] Embodiment 52. The pharmaceutical composition of Embodiment 50 or 51, wherein said pharmaceutically acceptable excipient comprises phosphate-buffered saline (PBS), .alpha.,.alpha.-trehalose dehydrate, L-histidine monohydrochloride monohydrate, polysorbate 20, NaCl, NaH2PO4, Na2HPO4, KH2PO4, K2HPO4, poloxamer 188, or any combination thereof.
[0220] Embodiment 53. The pharmaceutical composition of Embodiment 50 or 51, wherein said pharmaceutically acceptable excipient is selected from phosphate-buffered saline (PBS), .alpha.,.alpha.-trehalose dehydrate, L-histidine monohydrochloride monohydrate, polysorbate 20, NaCl, NaH2PO4, Na2HPO4, KH2PO4, K2HPO4, poloxamer 188, and any combination thereof.
[0221] Embodiment 54. The pharmaceutical composition of Embodiment 50 or 51, wherein said pharmaceutically acceptable excipient comprises poloxamer 188.
[0222] Embodiment 55. The pharmaceutical composition of Embodiment 54, wherein said pharmaceutically acceptable excipient comprises 0.0001%-0.01% poloxamer 188.
[0223] Embodiment 56. The pharmaceutical composition of Embodiment 55, wherein said pharmaceutically acceptable excipient comprises 0.001% poloxamer 188.
[0224] Embodiment 57. The pharmaceutical composition of any one of Embodiments 50-56, wherein said pharmaceutically acceptable excipient further comprises one or more salts.
[0225] Embodiment 58. The pharmaceutical composition of Embodiment 57, wherein said one or more salts comprises NaCl, NaH2PO4, Na2HPO4, and KH2PO4.
[0226] Embodiment 59. The pharmaceutical composition of Embodiment 57, wherein said one or more salts comprises 80 mM NaCl, 5 mM NaH2PO4, 40 mM Na2HPO4, and 5 mM KH2PO4.
[0227] Embodiment 60. The pharmaceutical composition of any one of Embodiments 49-59, wherein said pharmaceutical composition has a pH of 6-8.
[0228] Embodiment 61. The pharmaceutical composition of Embodiment 60, wherein said pharmaceutical composition has a pH of 7.2-7.4.
[0229] Embodiment 62. The pharmaceutical composition of Embodiment 61, wherein said pharmaceutical composition has a pH of 7.3.
[0230] Embodiment 63. The pharmaceutical composition of any one of Embodiments 49-62, wherein said pharmaceutical composition has a viral titer of at least 1.0.times.1010 vg/m L.
[0231] Embodiment 64. The pharmaceutical composition of Embodiment 63, wherein said pharmaceutical composition has a viral titer of at least 5.0.times.1010 vg/mL.
[0232] Embodiment 65. The pharmaceutical composition of any one of Embodiments 49-64, when said pharmaceutical composition is subject to five freeze/thaw cycles, said pharmaceutical composition retains at least 60%, 70%, 80%, or 90% of a viral titer as compared to the viral titer prior to the five freeze/thaw cycles.
[0233] Embodiment 66. The pharmaceutical composition of any one of Embodiments 49-65, wherein said pharmaceutical composition, when administered to a patient with Leber's hereditary optic neuropathy, generates a higher average recovery of vision than a comparable pharmaceutical composition without said recombinant nucleic acid.
[0234] Embodiment 67. The pharmaceutical composition of any one of Embodiments 49-66, wherein said pharmaceutical composition, when administered to a patient with Leber's hereditary optic neuropathy, generates a higher average recovery of vision than a comparable pharmaceutical composition comprising a recombinant nucleic acid as set forth in SEQ ID NO: 15.
[0235] Embodiment 68. A method of treating an eye disorder, comprising administering said pharmaceutical composition of any one of Embodiments 49-67 to a patient in need thereof.
[0236] Embodiment 69. The method of Embodiment 68, wherein said eye disorder is Leber's hereditary optic neuropathy (LHON).
[0237] Embodiment 70. The method of Embodiment 68 or 69, comprising administering said pharmaceutical composition to one or both eyes of said patient.
[0238] Embodiment 71. The method of any one of Embodiments 68-70, wherein said pharmaceutical composition is administered via intraocular or intravitreal injection.
[0239] Embodiment 72. The method of Embodiment 71, wherein said pharmaceutical composition is administered via intravitreal injection.
[0240] Embodiment 73. The method of Embodiment 72, wherein about 0.01-0.1 mL of said pharmaceutical composition is administered via intravitreal injection.
[0241] Embodiment 74. The method of Embodiment 73, wherein about 0.05 mL of said pharmaceutical composition is administered via intravitreal injection.
[0242] Embodiment 75. The method of any one of Embodiments 68-74, further comprising administering methylprednisolone to said patient.
[0243] Embodiment 76. The method of Embodiment 75, wherein said methylprednisolone is administered prior to said intravitreal injection of said pharmaceutical composition.
[0244] Embodiment 77. The method of Embodiment 75 or 76, wherein said methylprednisolone is administered orally.
[0245] Embodiment 78. The method of any one of Embodiments 75-77, wherein said methylprednisolone is administered daily for at least 1, 2, 3, 4, 5, 6, or 7 days prior to said intravitreal injection of said pharmaceutical composition.
[0246] Embodiment 79. The method of any one of Embodiments 75-78, wherein said methylprednisolone is administered daily.
[0247] Embodiment 80. The method of any one of Embodiments 75-79, wherein a daily dosage of about 32 mg/60 kg methylprednisolone is administered.
[0248] Embodiment 81. The method of any one of Embodiments 75-80, wherein said methylprednisolone is administered after said intravitreal injection of said pharmaceutical composition.
[0249] Embodiment 82. The method of any one of Embodiments 75-81, further comprising administering creatine phosphate sodium to said patient.
[0250] Embodiment 83. The method of Embodiment 82, wherein said creatine phosphate sodium is administered intravenously.
[0251] Embodiment 84. The method of any one of Embodiments 75-83, wherein said methylprednisolone is administered intravenously or orally.
[0252] Embodiment 85. The method of any one of Embodiments 75-84, comprising administering methylprednisolone intravenously for at least one day, which is followed by administering methylprednisolone orally for at least a week.
[0253] Embodiment 86. The method of Embodiment 85, comprising administering methylprednisolone intravenously for about 3 days, which is followed by administering methylprednisolone orally for at least about 6 weeks.
[0254] Embodiment 87. The method of any one of Embodiments 75-86, wherein said methylprednisolone is administered intravenously at a daily dose of about 80 mg/60 kg.
[0255] Embodiment 88. The method of any one of Embodiments 75-87, wherein said administering said pharmaceutical composition generates a higher average recovery of vision than a comparable pharmaceutical composition without said recombinant nucleic acid.
[0256] Embodiment 89. The method of any one of Embodiments 75-88, wherein said administering said pharmaceutical composition generates a higher average recovery of vision than a comparable pharmaceutical composition comprising a recombinant nucleic acid as set forth in SEQ ID NO: 25.
EXAMPLES
[0257] The following exemplary embodiments further describe the present invention. It should be understood that these examples are only intended to illustrate the invention, but not to limit the scope of the present invention. Unless otherwise indicated, the methods and conditions disclosed in e.g., sambrook et al, molecular cloning: a laboratory manual (New York: cold spring harbor laboratory press, 1989) or the conditions recommended by the manufacturer can be used in the examples below.
Example 1-- ND1 Plasmid and Virus Preparation
1.1 Plasmid Preparation
[0258] The nucleotide sequence for human ND1 was obtained based on US National Center for Biotechnology Information reference Gene ID 4535 (SEQ ID NO: 163). The mitochondrial targeting sequence is derived from COX10 (e.g., as shown in SEQ ID NO: 1 and 3). The optimized nucleotide sequence of human ND1 (e.g., SEQ ID NO: 11 and 12, referred herein as ND1 and optimized ND1) were designed to improve the transcription efficiency and/or the translation efficiency. The optimized COX10-opt_ND1 sequence is about 81% homology to COX10-ND1 (as shown in FIG. 4), and the GC content is raised from 49.45% to 64.26% after codon-optimization, and therefore has improved gene transcription efficiency and protein translation efficiency. The 3' of the optimized opt_ND1 gene was followed by an untranslated region (i.e., 3'UTR, SEQ ID NO: 13) to form a recombinant nucleic acid, COX10-opt_ND1-3'UTR (as shown in SEQ ID NO: 27).
[0259] The synthesized recombinant nucleic acid, COX10-opt_ND1-3'UTR and the AAV vector was cut by restriction enzymes to form cohesive ends, and then the recombinant nucleic acid was embedded into the rAAV vector to form generate the rAAV-optimized ND1 plasmid (i.e., the rAAV2-opt_ND1 plasmid). The rAAV2-opt_ND1 plasmid was compared to the rAAV2-ND1 plasmid which comprises the COX10-ND1 nucleic acid. The plasmid was cultured at 37.degree. C. in a LB plate with Kanamycin. Blue colonies and white colonies appeared, where white colonies were recombinant clones. The white colonies were picked, added to 100 mg/L kanamycin-containing LB culture medium, cultured at 37.degree. C., 200 rpm for 8 hours and then the plasmid were extracted from the cultured bacterial medium.
[0260] 1.2 Cell Transfection
[0261] One day before transfection, HEK293 cells were inoculated to 225 cm2 cell culture bottle: at the inoculation density of 3.0.times.107 cells/ml, the culture medium was the Dulbecco's Modified Eagle Medium (DMEM) with 10% bovine serum, at 37.degree. C. in a 5% CO2 incubator overnight. The culture medium were replaced with fresh DMEM with 10% bovine serum on the day of transfection. After the cells grow to 80-90%, the culture medium was discarded and cells were transfected with the rAAV2-ND1 and rAAV2-opt_ND1 plasmid. The cells were collected 48 h after the transfection.
[0262] 1.3 Collection, Concentration and Purification of the Recombinant Adeno-Associated Virus
[0263] Virus collection: 1) dry ice ethanol bath (or liquid nitrogen) and a 37.degree. C. water bath were prepared; 2) the transfected cells along with media were collected in a 15 ml centrifuge tube; 3) the cells were centrifuged for 3 minutes at 1000 rpm/min, the cells and supernatant were separated; the supernatant were stored separately; and the cells were re-suspended in 1 ml of PBS; 4) the cell suspension were transferred between the dry ice-ethanol bath and 37.degree. C. water bath repeatedly, freeze thawing for four times for 10 minutes each, slightly shaking after each thawing.
[0264] Virus concentration: 1) cell debris were removed with 10,000 g centrifugation; the centrifugal supernatant was transferred to a new centrifuge tube; 2) adding benzonase nuclease was added to remove residual plasmid DNA (final concentration at 50 U/ml). The tube was inverted several times to mix thoroughly and then incubated at 37.degree. C. for 30 minutes; 3) the sample was filtered with a 0.45 .mu.m filtration head; the filtrate is the concentrated rAAV2 virus.
[0265] Virus purification: 1) Iodixanol at final concentrations of 60%, 50%, 40%, or 25% was added to the concentrated virus solution; 2) samples were centrifuged at 50,000 g for 4 hours to form a density gradient. The enriched rAAV2 particles were collected near the fraction with 50% iodixanol; 3) viruses were loaded to a dialysis column bag and eluted for 10 times to obtain the purified recombinant AAV virus.
[0266] Accordingly, the concentrated, purified AAV particles comprising rAAV2-ND1 and rAAV2-opt_ND1 were obtained.
[0267] Similarly, other mitochondrial targeting sequences (MTS), such as OPA1 (SEQ ID NO: 5) can be used to replace COX10 in the above example and create AAV with recombinant plasmids. Mitochondria targeting peptide encoded by COX10 and OPA1 can direct the protein encoded by the optimized ND1 nucleic acid to the inner membrane of mitochondria, thereby achieving mitochondria targeted expression of protein.
Example 2-- Expression of ND1 Protein in HEK293 Cells Using COX10-ND1 and Further Optimized COX10-Opt_ND1 Vectors
[0268] HEK293 cells were transduced with viral particle comprising 1) rAAV2-COX10-opt_ND1 (comprising SEQ ID NO: 27) or 2) rAAV2-COX10-ND1 (comprising SEQ ID NO: 25) at MOI of 10,000. PBS was used for the control group. Cellular proteins were extracted 48 hours after transduction for analysis by western blotting. .beta.-actin was used as loading control. As shown in FIG. 5, the results indicated that ND1 expression level in cells transduced with the optimized rAAV2-COX10-opt_ND1 is 2.1 times of the ND1 expression level in cells transduced with the non-optimized COX10-ND1. In FIG. 5, lane 1 is PBS control, lane 2 is rAAV2-COX10-ND1 group, and lane 3 is rAAV2-COX10-opt_ND1 group.
Example 3-- Expression and Mitochondria Localization of Human AAV2-ND1 in HEK293 Cells
[0269] We have conducted fluorescence microscopy/staining experiment to show that the mitochondria targeting sequence (MTS) can direct ND1 protein into mitochondria, suggesting that it is feasible to use these constructs to treat LHON.
[0270] Here, 293 cells and RGC-5 cells were transduced with corresponding rAAV2-ND1-ZsGreen at MOI of 106. 48 hours after viral transduction, we used fluorescence microscopy to monitor the expression of green fluorescence protein and cell condition. Mitochondria was stained with MitoTracker and cell nucleus were stained with DAPI after fixation using 4% paraformadyhyde.
[0271] As shown in FIG. 6, mitochondria was labeled with MitoTracker and shown in red color, ND1-ZsGreen protein was shown in green color. According to laser confocal microscopy, ND1 proteins were co-localized with mitochondria (as shown in the merged yellow color) in 293 cells and RGC-5 cells. The results showed that the ND1 constructs carrying MTS result in expression of ND1 protein in mitochondria.
Example 4-- Dynamics of Expression of AAV2-ND1 in HEK293 Cells
[0272] To study the change of ND1 mRNA expression over time after rAAV2-ND1 transduction in cells, we collected cell samples at different time points and analyzed ND1 mRNA expression level using RT-PCT.
[0273] Briefly, 293 cells were cultured and transduced with viral particles at MOI of 104 or 105. RT-PCR was conducted using the following primers for ND1 and GAPDH (as control):
TABLE-US-00002 ND1-F: (SEQ ID NO: 164) GAGGCTCTGTCTGGTATCTTGAA ND1-R: (SEQ ID NO: 165) GTCGGGGCGGTGATGTAG GAPDH-F: (SEQ ID NO: 166) CCTGTACGCCAACACAGTGC GAPDH-R: (SEQ ID NO: 167) ATACTCCTGCTTGCTGATCC
[0274] According to FIG. 7, the results showed that ND1 mRNA expression reached peak value at about 72 hours after transduction at MOI of 105, and decreased afterwards, suggesting that rAAV2-ND1 can effectively transduce cells.
Example 5-- Exploratory Study of ND1 Expression in C57BL/6J Mice with Intravitreal Injection of rAAV2-ND1
[0275] C57BL/6J mice received intravitreal injection of rAAV2-ND1 (at 1 pL injection volume) and eye samples were analyzed 1 day, 5 days, 10 days, or 30 days after injection. RNA were extracted from the sample and RT-PCT was performed to analyze the expression level. As shown in FIG. 8, the results indicated that rAAV-ND1 can be expressed in mice eye and the mRNA expression level continued to increase from 7 days post-injection to 30 days post-injection.
Example 6-- ND1 Protein Expression in HEK293 Cells Transduced with rAAV2-ND1
[0276] 293 cells were transduced with rAAV2-ND1 viruses at MOI of 105 and ND1 protein expression was analyzed by Western blotting. As shown in FIG. 9, the results indicated that rAAV2-ND1 can successfully transduce cells and induce ND1 expression.
Example 7-- Safety Study of rAAV2-ND1 Using Rabbit Model
[0277] Eight rabbits were divided into 2 group. rAAV2-ND1 virus solution (1.times.1010 vg/0.05 mL) or PBS control solution was punctured into the vitreous cavity from 3 mm outside the corneal limbus at the pars plana. Blood samples were collected for routine blood tests and cytokine analysis 1-month and 2-month post-injection.
[0278] Tables 2 and 3 below showed the results of the routine blood tests, including white blood cell count (WBC), red blood cell count (RBC), hemoglobulin (HGB), hematocrit (HCT), platelet (PLT), mean platelet volume (MPV), platelet hema-tocrit (PCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and neutrophil ratio (NEUT %). The results showed no significant differences between the rAAV2-ND1 virus injected group and the PBS control group, indicating that injection of rAAV2-ND1 is safe.
TABLE-US-00003 TABLE 2 Routine Blood Test Results: 1-month Post-injection 1-month WBC RBC HGB HCT PLT MPV PBS Control 10.0 .+-. 1.7 6.1 .+-. 0.4 128.4 .+-. 7.6 39.2 .+-. 2.3 425.0 .+-. 74.3 6.6 .+-. 0.2 rAAV2-ND1 10.9 .+-. 2.6 6.3 .+-. 0.4 132.0 .+-. 6.7 40.4 .+-. 2.0 363.9 .+-. 144.1 7.1 .+-. 0.4 1-month PCT MCV MCH MCHC NEUT % PBS Control 0.3 .+-. 0.1 64.6 .+-. 1.9 21.2 .+-. 0.5 327.4 .+-. 6.5 48.4 .+-. 8.5 rAAV2-ND1 0.3 .+-. 0.1 64.5 .+-. 3.4 21.1 .+-. 0.9 326.9 .+-. 6.1 38.7 .+-. 8.6
TABLE-US-00004 TABLE 3 Routine Blood Test Results: 2-month Post-injection 2-month WBC RBC HGB HCT PLT MPV PBS Control 8.9 .+-. 4.1 6.5 .+-. 0.5 139.6 .+-. 10.2 41.6 .+-. 3.1 284.0 .+-. 120 7.8 .+-. 0.6 rAAV2-ND1 7.6 .+-. 1.6 6.8 .+-. 0.2 144.7 .+-. 5.7 42.8 .+-. 1.4 326.6 .+-. 130 7.9 .+-. 0.6 2-month PCT MCV MCH MCHC NEUT % PBS Control 0.2 .+-. 0.1 64.4 .+-. 3.2 21.6 .+-. 1.1 335.6 .+-. 6.9 32.9 .+-. 6.9 rAAV2-ND1 0.3 .+-. 0.1 63.0 .+-. 1.7 21.3 .+-. 0.5 338.1 .+-. 8.9 40.2 .+-. 8.3
[0279] As shown in FIG. 10, cytokine analysis of blood samples 1-month and 2-month post-injection showed that there was no significant differences of cytokine levels (TNF-.alpha.,IFN-.gamma.,IL-6) between rAAV2-ND1 virus injected group and the PBS control group, indicating that injection of rAAV2-ND1 does not generate immune response, is safe and without immunogenicity.
Example 8--Other Fusion Proteins
[0280] Similar experimental methods in examples 1-7 can be followed using other fusion proteins as set forth in SEQ ID NO: 15-84. And similar results are expected to be achieved.
[0281] While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.
Sequence CWU
1
1
169184DNAHomo sapiens 1atggccgcat ctccgcacac tctctcctca cgcctcctga
caggttgcgt aggaggctct 60gtctggtatc ttgaaagaag aact
84284DNAArtificial Sequenceopt_COX10 2atggccgcct
ctccacacac actgagtagc agactgctga ccggctgtgt tggcggctct 60gtgtggtatc
tggaacggcg gaca
84384DNAArtificial Sequenceopt_COX10* 3atggccgcca gcccccacac cctgagcagc
cgcctgctga ccggctgcgt gggcggcagc 60gtgtggtacc tggagcgccg cacc
84487DNAArtificial SequenceCOX8
4atgtccgtcc tgacgcgcct gctgctgcgg ggcttgacac ggctcggctc ggcggctcca
60gtgcggcgcg ccagaatcca ttcgttg
875266DNAHomo sapiens 5gtgctgcccg cctagaaagg gtgaagtggt tgtttccgtg
acggactgag tacgggtgcc 60tgtcaggctc ttgcggaagt ccatgcgcca ttgggagggc
ctcggccgcg gctctgtgcc 120cttgctgctg agggccactt cctgggtcat tcctggaccg
ggagccgggc tggggctcac 180acgggggctc ccgcgtggcc gtctcggcgc ctgcgtgacc
tccccgccgg cgggatgtgg 240cgactacgtc gggccgctgt ggcctg
26661380DNAHomo sapiens 6atgctaaaac taatcgtccc
aacaattatg ttactaccac tgacatggct ttccaaaaaa 60cacatgattt ggatcaacac
aaccacccac agcctaatta ttagcatcat ccctctacta 120ttttttaacc aaatcaacaa
caacctattt agctgttccc caaccttttc ctccgacccc 180ctaacaaccc ccctcctaat
gctaactacc tggctcctac ccctcacaat catggcaagc 240caacgccact tatccagtga
accactatca cgaaaaaaac tctacctctc tatgctaatc 300tccctacaaa tctccttaat
tatgacattc acagccacag aactaatcat gttttatatc 360ttcttcgaaa ccacacttat
ccccaccttg gctatcatca cccgatgggg caaccagcca 420gaacgcctga acgcaggcac
atacttccta ttctacaccc tagtaggctc ccttccccta 480ctcatcgcac taatttacac
tcacaacacc ctaggctcac taaacattct actactcact 540ctcactgccc aagaactatc
aaactcctgg gccaacaact taatgtggct agcttacaca 600atggctttta tggtaaagat
gcctctttac ggactccact tatggctccc taaagcccat 660gtcgaagccc ccatcgctgg
gtcaatggta cttgccgcag tactcttaaa actaggcggc 720tatggtatga tgcgcctcac
actcattctc aaccccctga caaaacacat ggcctacccc 780ttccttgtac tatccctatg
gggcatgatt atgacaagct ccatctgcct acgacaaaca 840gacctaaaat cgctcattgc
atactcttca atcagccaca tggccctcgt agtaacagcc 900attctcatcc aaaccccctg
gagcttcacc ggcgcagtca ttctcatgat cgcccacggg 960cttacatcct cattactatt
ctgcctagca aactcaaact acgaacgcac tcacagtcgc 1020atcatgatcc tctctcaagg
acttcaaact ctactcccac taatggcttt ttggtggctt 1080ctagcaagcc tcgctaacct
cgccttaccc cccactatta acctactggg agaactctct 1140gtgctagtaa ccacgttctc
ctggtcaaat atcactctcc tacttacagg actcaacatg 1200ctagtcacag ccctatactc
cctctacatg tttaccacaa cacaatgggg ctcactcacc 1260caccacatta acaacatgaa
accctcattc acacgagaaa acaccctcat gttcatgcac 1320ctatccccca ttctcctcct
atccctcaac cccgacatca ttaccgggtt ttcctcttaa 138071380DNAArtificial
Sequenceopt_ND4 7atgctgaagc tgatcgtgcc caccatcatg ctgctgcctc tgacctggct
gagcaagaaa 60cacatgatct ggatcaacac caccacgcac agcctgatca tcagcatcat
ccctctgctg 120ttcttcaacc agatcaacaa caacctgttc agctgcagcc ccaccttcag
cagcgaccct 180ctgacaacac ctctgctgat gctgaccacc tggctgctgc ccctcacaat
catggcctct 240cagagacacc tgagcagcga gcccctgagc cggaagaaac tgtacctgag
catgctgatc 300tccctgcaga tctctctgat catgaccttc accgccaccg agctgatcat
gttctacatc 360tttttcgaga caacgctgat ccccacactg gccatcatca ccagatgggg
caaccagcct 420gagagactga acgccggcac ctactttctg ttctacaccc tcgtgggcag
cctgccactg 480ctgattgccc tgatctacac ccacaacacc ctgggctccc tgaacatcct
gctgctgaca 540ctgacagccc aagagctgag caacagctgg gccaacaatc tgatgtggct
ggcctacaca 600atggccttca tggtcaagat gcccctgtac ggcctgcacc tgtggctgcc
taaagctcat 660gtggaagccc ctatcgccgg ctctatggtg ctggctgcag tgctgctgaa
actcggcggc 720tacggcatga tgcggctgac cctgattctg aatcccctga ccaagcacat
ggcctatcca 780tttctggtgc tgagcctgtg gggcatgatt atgaccagca gcatctgcct
gcggcagacc 840gatctgaagt ccctgatcgc ctacagctcc atcagccaca tggccctggt
ggtcaccgcc 900atcctgattc agaccccttg gagctttaca ggcgccgtga tcctgatgat
tgcccacggc 960ctgacaagca gcctgctgtt ttgtctggcc aacagcaact acgagcggac
ccacagcaga 1020atcatgatcc tgtctcaggg cctgcagacc ctcctgcctc ttatggcttt
ttggtggctg 1080ctggcctctc tggccaatct ggcactgcct cctaccatca atctgctggg
cgagctgagc 1140gtgctggtca ccacattcag ctggtccaat atcaccctgc tgctcaccgg
cctgaacatg 1200ctggttacag ccctgtactc cctgtacatg ttcaccacca cacagtgggg
aagcctgaca 1260caccacatca acaatatgaa gcccagcttc acccgcgaga acaccctgat
gttcatgcat 1320ctgagcccca ttctgctgct gtccctgaat cctgatatca tcaccggctt
ctccagctga 138081380DNAArtificial Sequenceopt_ND4* 8atgctgaagc
tgatcgtgcc caccatcatg ctgctgcccc tgacctggct gagcaagaag 60cacatgatct
ggatcaacac caccacccac agcctgatca tcagcatcat ccccctgctg 120ttcttcaacc
agatcaacaa caacctgttc agctgcagcc ccaccttcag cagcgacccc 180ctgaccaccc
ccctgctgat gctgaccacc tggctgctgc ccctgaccat catggccagc 240cagcgccacc
tgagcagcga gcccctgagc cgcaagaagc tgtacctgag catgctgatc 300agcctgcaga
tcagcctgat catgaccttc accgccaccg agctgatcat gttctacatc 360ttcttcgaga
ccaccctgat ccccaccctg gccatcatca cccgctgggg caaccagccc 420gagcgcctga
acgccggcac ctacttcctg ttctacaccc tggtgggcag cctgcccctg 480ctgatcgccc
tgatctacac ccacaacacc ctgggcagcc tgaacatcct gctgctgacc 540ctgaccgccc
aggagctgag caacagctgg gccaacaacc tgatgtggct ggcctacacc 600atggccttca
tggtgaagat gcccctgtac ggcctgcacc tgtggctgcc caaggcccac 660gtggaggccc
ccatcgccgg cagcatggtg ctggccgccg tgctgctgaa gctgggcggc 720tacggcatga
tgcgcctgac cctgatcctg aaccccctga ccaagcacat ggcctacccc 780ttcctggtgc
tgagcctgtg gggcatgatc atgaccagca gcatctgcct gcgccagacc 840gacctgaaga
gcctgatcgc ctacagcagc atcagccaca tggccctggt ggtgaccgcc 900atcctgatcc
agaccccctg gagcttcacc ggcgccgtga tcctgatgat cgcccacggc 960ctgaccagca
gcctgctgtt ctgcctggcc aacagcaact acgagcgcac ccacagccgc 1020atcatgatcc
tgagccaggg cctgcagacc ctgctgcccc tgatggcctt ctggtggctg 1080ctggccagcc
tggccaacct ggccctgccc cccaccatca acctgctggg cgagctgagc 1140gtgctggtga
ccaccttcag ctggagcaac atcaccctgc tgctgaccgg cctgaacatg 1200ctggtgaccg
ccctgtacag cctgtacatg ttcaccacca cccagtgggg cagcctgacc 1260caccacatca
acaacatgaa gcccagcttc acccgcgaga acaccctgat gttcatgcac 1320ctgagcccca
tcctgctgct gagcctgaac cccgacatca tcaccggctt cagcagctaa 13809525DNAHomo
sapiens 9atgatgtatg ctttgtttct gttgagtgtg ggtttagtaa tggggtttgt
ggggttttct 60tctaagcctt ctcctattta tgggggttta gtattgattg ttagcggtgt
ggtcgggtgt 120gttattattc tgaattttgg gggaggttat atgggtttaa tggttttttt
aatttattta 180gggggaatga tggttgtctt tggatatact acagcgatgg ctattgagga
gtatcctgag 240gcatgggggt caggggttga ggtcttggtg agtgttttag tggggttagc
gatggaggta 300ggattggtgc tgtgggtgaa agagtatgat ggggtggtgg ttgtggtaaa
ctttaatagt 360gtaggaagct ggatgattta tgaaggagag gggtcagggt tgattcggga
ggatcctatt 420ggtgcggggg ctttgtatga ttatgggcgt tggttagtag tagttactgg
ttggacattg 480tttgttggtg tatatattgt aattgagatt gctcggggga attag
52510525DNAArtificial Sequenceopt_ND6 10atgatgtacg ccctgttcct
gctgagcgtg ggcctggtga tgggcttcgt gggcttcagc 60agcaagccca gccccatcta
cggcggcctg gtgctgatcg tgagcggcgt ggtgggctgc 120gtgatcatcc tgaacttcgg
cggcggctac atgggcctga tggtgttcct gatctacctg 180ggcggcatga tggtggtgtt
cggctacacc accgccatgg ccatcgagga gtaccccgag 240gcctggggca gcggcgtgga
ggtgctggtg agcgtgctgg tgggcctggc catggaggtg 300ggcctggtgc tgtgggtgaa
ggagtacgac ggcgtggtgg tggtggtgaa cttcaacagc 360gtgggcagct ggatgatcta
cgagggcgag ggcagcggcc tgatccgcga ggaccccatc 420ggcgccggcg ccctgtacga
ctacggccgc tggctggtgg tggtgaccgg ctggaccctg 480ttcgtgggcg tgtacatcgt
gatcgagatc gcccgcggca actaa 52511957DNAHomo sapiens
11atgcccatgg ccaacctcct actcctcatt gtacccattc taatcgcaat ggcattccta
60atgcttaccg aacgaaaaat tctaggctat atgcaactac gcaaaggccc caacgttgta
120ggcccctacg ggctactaca acccttcgct gacgccatga aactcttcac caaagagccc
180ctaaaacccg ccacatctac catcaccctc tacatcaccg ccccgacctt agctctcacc
240atcgctcttc tactatggac ccccctcccc atgcccaacc ccctggtcaa cctcaaccta
300ggcctcctat ttattctagc cacctctagc ctagccgttt actcaatcct ctggtcaggg
360tgggcatcaa actcaaacta cgccctgatc ggcgcactgc gagcagtagc ccaaacaatc
420tcatatgaag tcaccctagc catcattcta ctatcaacat tactaatgag tggctccttt
480aacctctcca cccttatcac aacacaagaa cacctctggt tactcctgcc atcatggccc
540ttggccatga tgtggtttat ctccacacta gcagagacca accgaacccc cttcgacctt
600gccgaagggg agtccgaact agtctcaggc ttcaacatcg aatacgccgc aggccccttc
660gccctattct tcatggccga atacacaaac attattatga tgaacaccct caccactaca
720atcttcctag gaacaacata tgacgcactc tcccctgaac tctacacaac atattttgtc
780accaagaccc tacttctaac ctccctgttc ttatggattc gaacagcata cccccgattc
840cgctacgacc aactcatgca cctcctatgg aaaaacttcc taccactcac cctagcatta
900cttatgtggt atgtctccat gcccattaca atctccagca ttccccctca aacctaa
95712957DNAArtificial Sequenceopt_ND1 12atgcccatgg ccaacctgct gctgctgatc
gtgcccatcc tgatcgccat ggccttcctg 60atgctgaccg agcgcaagat cctgggctac
atgcagctgc gcaagggccc caacgtggtg 120ggcccctacg gcctgctgca gcccttcgcc
gacgccatga agctgttcac caaggagccc 180ctgaagcccg ccaccagcac catcaccctg
tacatcaccg cccccaccct ggccctgacc 240atcgccctgc tgctgtggac ccccctgccc
atgcccaacc ccctggtgaa cctgaacctg 300ggcctgctgt tcatcctggc caccagcagc
ctggccgtgt acagcatcct gtggagcggc 360tgggccagca acagcaacta cgccctgatc
ggcgccctgc gcgccgtggc ccagaccatc 420agctacgagg tgaccctggc catcatcctg
ctgagcaccc tgctgatgag cggcagcttc 480aacctgagca ccctgatcac cacccaggag
cacctgtggc tgctgctgcc cagctggccc 540ctggccatga tgtggttcat cagcaccctg
gccgagacca accgcacccc cttcgacctg 600gccgagggcg agagcgagct ggtgagcggc
ttcaacatcg agtacgccgc cggccccttc 660gccctgttct tcatggccga gtacaccaac
atcatcatga tgaacaccct gaccaccacc 720atcttcctgg gcaccaccta cgacgccctg
agccccgagc tgtacaccac ctacttcgtg 780accaagaccc tgctgctgac cagcctgttc
ctgtggatcc gcaccgccta cccccgcttc 840cgctacgacc agctgatgca cctgctgtgg
aagaacttcc tgcccctgac cctggccctg 900ctgatgtggt acgtgagcat gcccatcacc
atcagcagca tcccccccca gacctaa 957131425DNAHomo sapiens 13gagcactggg
acgcccaccg cccctttccc tccgctgcca ggcgagcatg ttgtggtaat 60tctggaacac
aagaagagaa attgctgggt ttagaacaag attataaacg aattcggtgc 120tcagtgatca
cttgacagtt tttttttttt ttaaatatta cccaaaatgc tccccaaata 180agaaatgcat
cagctcagtc agtgaataca aaaaaggaat tatttttccc tttgagggtc 240ttttatacat
ctctcctcca accccaccct ctattctgtt tcttcctcct cacatggggg 300tacacataca
cagcttcctc ttttggttcc atccttacca ccacaccaca cgcacactcc 360acatgcccag
cagagtggca cttggtggcc agaaagtgtg agcctcatga tctgctgtct 420gtagttctgt
gagctcaggt ccctcaaagg cctcggagca cccccttcct tgtgactgag 480ccagggcctg
catttttggt tttccccacc ccacacattc tcaaccatag tccttctaac 540aataccaata
gctaggaccc ggctgctgtg cactgggact ggggattcca catgtttgcc 600ttgggagtct
caagctggac tgccagcccc tgtcctccct tcacccccat tgcgtatgag 660catttcagaa
ctccaaggag tcacaggcat ctttatagtt cacgttaaca tatagacact 720gttggaagca
gttccttcta aaagggtagc cctggactta ataccagccg gatacctctg 780gcccccaccc
cattactgta cctctggagt cactactgtg ggtcgccact cctctgctac 840acagcacggc
tttttcaagg ctgtattgag aagggaagtt aggaagaagg gtgtgctggg 900ctaaccagcc
cacagagctc acattcctgt cccttgggtg aaaaatacat gtccatcctg 960atatctcctg
aattcagaaa ttagcctcca catgtgcaat ggctttaaga gccagaagca 1020gggttctggg
aattttgcaa gttacctgtg gccaggtgtg gtctcggtta ccaaatacgg 1080ttacctgcag
ctttttagtc ctttgtgctc ccacgggtct acagagtccc atctgcccaa 1140aggtcttgaa
gcttgacagg atgttttcga ttactcagtc tcccagggca ctactggtcc 1200gtaggattcg
attggtcggg gtaggagagt taaacaacat ttaaacagag ttctctcaaa 1260aatgtctaaa
gggattgtag gtagataaca tccaatcact gtttgcactt atctgaaatc 1320ttccctcttg
gctgccccca ggtatttact gtggagaaca ttgcatagga atgtctggaa 1380aaagcttcta
caacttgtta cagccttcac atttgtagaa gcttt 142514625DNAHomo
sapiens 14gagcactggg acgcccaccg cccctttccc tccgctgcca ggcgagcatg
ttgtggtaat 60tctggaacac aagaagagaa attgctgggt ttagaacaag attataaacg
aattcggtgc 120tcagtgatca cttgacagtt tttttttttt ttaaatatta cccaaaatgc
tccccaaata 180agaaatgcat cagctcagtc agtgaataca aaaaaggaat tatttttccc
tttgagggtc 240ttttatacat ctctcctcca accccaccct ctattctgtt tcttcctcct
cacatggggg 300tacacataca cagcttcctc ttttggttcc atccttacca ccacaccaca
cgcacactcc 360acatgcccag cagagtggca cttggtggcc agaaagtgtg agcctcatga
tctgctgtct 420gtagttctgt gagctcaggt ccctcaaagg cctcggagca cccccttcct
tgtgactgag 480ccagggcctg catttttggt tttccccacc ccacacattc tcaaccatag
tccttctaac 540aataccaata gctaggaccc ggctgctgtg cactgggact ggggattcca
catgtttgcc 600ttgggagtct caagctggac tgcca
625152889DNAArtificial SequenceCOX10-ND4-3'UTR 15atggccgcat
ctccgcacac tctctcctca cgcctcctga caggttgcgt aggaggctct 60gtctggtatc
ttgaaagaag aactatgcta aaactaatcg tcccaacaat tatgttacta 120ccactgacat
ggctttccaa aaaacacatg atttggatca acacaaccac ccacagccta 180attattagca
tcatccctct actatttttt aaccaaatca acaacaacct atttagctgt 240tccccaacct
tttcctccga ccccctaaca acccccctcc taatgctaac tacctggctc 300ctacccctca
caatcatggc aagccaacgc cacttatcca gtgaaccact atcacgaaaa 360aaactctacc
tctctatgct aatctcccta caaatctcct taattatgac attcacagcc 420acagaactaa
tcatgtttta tatcttcttc gaaaccacac ttatccccac cttggctatc 480atcacccgat
ggggcaacca gccagaacgc ctgaacgcag gcacatactt cctattctac 540accctagtag
gctcccttcc cctactcatc gcactaattt acactcacaa caccctaggc 600tcactaaaca
ttctactact cactctcact gcccaagaac tatcaaactc ctgggccaac 660aacttaatgt
ggctagctta cacaatggct tttatggtaa agatgcctct ttacggactc 720cacttatggc
tccctaaagc ccatgtcgaa gcccccatcg ctgggtcaat ggtacttgcc 780gcagtactct
taaaactagg cggctatggt atgatgcgcc tcacactcat tctcaacccc 840ctgacaaaac
acatggccta ccccttcctt gtactatccc tatggggcat gattatgaca 900agctccatct
gcctacgaca aacagaccta aaatcgctca ttgcatactc ttcaatcagc 960cacatggccc
tcgtagtaac agccattctc atccaaaccc cctggagctt caccggcgca 1020gtcattctca
tgatcgccca cgggcttaca tcctcattac tattctgcct agcaaactca 1080aactacgaac
gcactcacag tcgcatcatg atcctctctc aaggacttca aactctactc 1140ccactaatgg
ctttttggtg gcttctagca agcctcgcta acctcgcctt accccccact 1200attaacctac
tgggagaact ctctgtgcta gtaaccacgt tctcctggtc aaatatcact 1260ctcctactta
caggactcaa catgctagtc acagccctat actccctcta catgtttacc 1320acaacacaat
ggggctcact cacccaccac attaacaaca tgaaaccctc attcacacga 1380gaaaacaccc
tcatgttcat gcacctatcc cccattctcc tcctatccct caaccccgac 1440atcattaccg
ggttttcctc ttaagagcac tgggacgccc accgcccctt tccctccgct 1500gccaggcgag
catgttgtgg taattctgga acacaagaag agaaattgct gggtttagaa 1560caagattata
aacgaattcg gtgctcagtg atcacttgac agtttttttt ttttttaaat 1620attacccaaa
atgctcccca aataagaaat gcatcagctc agtcagtgaa tacaaaaaag 1680gaattatttt
tccctttgag ggtcttttat acatctctcc tccaacccca ccctctattc 1740tgtttcttcc
tcctcacatg ggggtacaca tacacagctt cctcttttgg ttccatcctt 1800accaccacac
cacacgcaca ctccacatgc ccagcagagt ggcacttggt ggccagaaag 1860tgtgagcctc
atgatctgct gtctgtagtt ctgtgagctc aggtccctca aaggcctcgg 1920agcaccccct
tccttgtgac tgagccaggg cctgcatttt tggttttccc caccccacac 1980attctcaacc
atagtccttc taacaatacc aatagctagg acccggctgc tgtgcactgg 2040gactggggat
tccacatgtt tgccttggga gtctcaagct ggactgccag cccctgtcct 2100cccttcaccc
ccattgcgta tgagcatttc agaactccaa ggagtcacag gcatctttat 2160agttcacgtt
aacatataga cactgttgga agcagttcct tctaaaaggg tagccctgga 2220cttaatacca
gccggatacc tctggccccc accccattac tgtacctctg gagtcactac 2280tgtgggtcgc
cactcctctg ctacacagca cggctttttc aaggctgtat tgagaaggga 2340agttaggaag
aagggtgtgc tgggctaacc agcccacaga gctcacattc ctgtcccttg 2400ggtgaaaaat
acatgtccat cctgatatct cctgaattca gaaattagcc tccacatgtg 2460caatggcttt
aagagccaga agcagggttc tgggaatttt gcaagttacc tgtggccagg 2520tgtggtctcg
gttaccaaat acggttacct gcagcttttt agtcctttgt gctcccacgg 2580gtctacagag
tcccatctgc ccaaaggtct tgaagcttga caggatgttt tcgattactc 2640agtctcccag
ggcactactg gtccgtagga ttcgattggt cggggtagga gagttaaaca 2700acatttaaac
agagttctct caaaaatgtc taaagggatt gtaggtagat aacatccaat 2760cactgtttgc
acttatctga aatcttccct cttggctgcc cccaggtatt tactgtggag 2820aacattgcat
aggaatgtct ggaaaaagct tctacaactt gttacagcct tcacatttgt 2880agaagcttt
2889162089DNAArtificial SequenceCOX10-ND4-3'UTR* 16atggccgcat ctccgcacac
tctctcctca cgcctcctga caggttgcgt aggaggctct 60gtctggtatc ttgaaagaag
aactatgcta aaactaatcg tcccaacaat tatgttacta 120ccactgacat ggctttccaa
aaaacacatg atttggatca acacaaccac ccacagccta 180attattagca tcatccctct
actatttttt aaccaaatca acaacaacct atttagctgt 240tccccaacct tttcctccga
ccccctaaca acccccctcc taatgctaac tacctggctc 300ctacccctca caatcatggc
aagccaacgc cacttatcca gtgaaccact atcacgaaaa 360aaactctacc tctctatgct
aatctcccta caaatctcct taattatgac attcacagcc 420acagaactaa tcatgtttta
tatcttcttc gaaaccacac ttatccccac cttggctatc 480atcacccgat ggggcaacca
gccagaacgc ctgaacgcag gcacatactt cctattctac 540accctagtag gctcccttcc
cctactcatc gcactaattt acactcacaa caccctaggc 600tcactaaaca ttctactact
cactctcact gcccaagaac tatcaaactc ctgggccaac 660aacttaatgt ggctagctta
cacaatggct tttatggtaa agatgcctct ttacggactc 720cacttatggc tccctaaagc
ccatgtcgaa gcccccatcg ctgggtcaat ggtacttgcc 780gcagtactct taaaactagg
cggctatggt atgatgcgcc tcacactcat tctcaacccc 840ctgacaaaac acatggccta
ccccttcctt gtactatccc tatggggcat gattatgaca 900agctccatct gcctacgaca
aacagaccta aaatcgctca ttgcatactc ttcaatcagc 960cacatggccc tcgtagtaac
agccattctc atccaaaccc cctggagctt caccggcgca 1020gtcattctca tgatcgccca
cgggcttaca tcctcattac tattctgcct agcaaactca 1080aactacgaac gcactcacag
tcgcatcatg atcctctctc aaggacttca aactctactc 1140ccactaatgg ctttttggtg
gcttctagca agcctcgcta acctcgcctt accccccact 1200attaacctac tgggagaact
ctctgtgcta gtaaccacgt tctcctggtc aaatatcact 1260ctcctactta caggactcaa
catgctagtc acagccctat actccctcta catgtttacc 1320acaacacaat ggggctcact
cacccaccac attaacaaca tgaaaccctc attcacacga 1380gaaaacaccc tcatgttcat
gcacctatcc cccattctcc tcctatccct caaccccgac 1440atcattaccg ggttttcctc
ttaagagcac tgggacgccc accgcccctt tccctccgct 1500gccaggcgag catgttgtgg
taattctgga acacaagaag agaaattgct gggtttagaa 1560caagattata aacgaattcg
gtgctcagtg atcacttgac agtttttttt ttttttaaat 1620attacccaaa atgctcccca
aataagaaat gcatcagctc agtcagtgaa tacaaaaaag 1680gaattatttt tccctttgag
ggtcttttat acatctctcc tccaacccca ccctctattc 1740tgtttcttcc tcctcacatg
ggggtacaca tacacagctt cctcttttgg ttccatcctt 1800accaccacac cacacgcaca
ctccacatgc ccagcagagt ggcacttggt ggccagaaag 1860tgtgagcctc atgatctgct
gtctgtagtt ctgtgagctc aggtccctca aaggcctcgg 1920agcaccccct tccttgtgac
tgagccaggg cctgcatttt tggttttccc caccccacac 1980attctcaacc atagtccttc
taacaatacc aatagctagg acccggctgc tgtgcactgg 2040gactggggat tccacatgtt
tgccttggga gtctcaagct ggactgcca 2089172889DNAArtificial
SequenceCOX10-opt_ND4-3'UTR 17atggccgcat ctccgcacac tctctcctca cgcctcctga
caggttgcgt aggaggctct 60gtctggtatc ttgaaagaag aactatgctg aagctgatcg
tgcccaccat catgctgctg 120cctctgacct ggctgagcaa gaaacacatg atctggatca
acaccaccac gcacagcctg 180atcatcagca tcatccctct gctgttcttc aaccagatca
acaacaacct gttcagctgc 240agccccacct tcagcagcga ccctctgaca acacctctgc
tgatgctgac cacctggctg 300ctgcccctca caatcatggc ctctcagaga cacctgagca
gcgagcccct gagccggaag 360aaactgtacc tgagcatgct gatctccctg cagatctctc
tgatcatgac cttcaccgcc 420accgagctga tcatgttcta catctttttc gagacaacgc
tgatccccac actggccatc 480atcaccagat ggggcaacca gcctgagaga ctgaacgccg
gcacctactt tctgttctac 540accctcgtgg gcagcctgcc actgctgatt gccctgatct
acacccacaa caccctgggc 600tccctgaaca tcctgctgct gacactgaca gcccaagagc
tgagcaacag ctgggccaac 660aatctgatgt ggctggccta cacaatggcc ttcatggtca
agatgcccct gtacggcctg 720cacctgtggc tgcctaaagc tcatgtggaa gcccctatcg
ccggctctat ggtgctggct 780gcagtgctgc tgaaactcgg cggctacggc atgatgcggc
tgaccctgat tctgaatccc 840ctgaccaagc acatggccta tccatttctg gtgctgagcc
tgtggggcat gattatgacc 900agcagcatct gcctgcggca gaccgatctg aagtccctga
tcgcctacag ctccatcagc 960cacatggccc tggtggtcac cgccatcctg attcagaccc
cttggagctt tacaggcgcc 1020gtgatcctga tgattgccca cggcctgaca agcagcctgc
tgttttgtct ggccaacagc 1080aactacgagc ggacccacag cagaatcatg atcctgtctc
agggcctgca gaccctcctg 1140cctcttatgg ctttttggtg gctgctggcc tctctggcca
atctggcact gcctcctacc 1200atcaatctgc tgggcgagct gagcgtgctg gtcaccacat
tcagctggtc caatatcacc 1260ctgctgctca ccggcctgaa catgctggtt acagccctgt
actccctgta catgttcacc 1320accacacagt ggggaagcct gacacaccac atcaacaata
tgaagcccag cttcacccgc 1380gagaacaccc tgatgttcat gcatctgagc cccattctgc
tgctgtccct gaatcctgat 1440atcatcaccg gcttctccag ctgagagcac tgggacgccc
accgcccctt tccctccgct 1500gccaggcgag catgttgtgg taattctgga acacaagaag
agaaattgct gggtttagaa 1560caagattata aacgaattcg gtgctcagtg atcacttgac
agtttttttt ttttttaaat 1620attacccaaa atgctcccca aataagaaat gcatcagctc
agtcagtgaa tacaaaaaag 1680gaattatttt tccctttgag ggtcttttat acatctctcc
tccaacccca ccctctattc 1740tgtttcttcc tcctcacatg ggggtacaca tacacagctt
cctcttttgg ttccatcctt 1800accaccacac cacacgcaca ctccacatgc ccagcagagt
ggcacttggt ggccagaaag 1860tgtgagcctc atgatctgct gtctgtagtt ctgtgagctc
aggtccctca aaggcctcgg 1920agcaccccct tccttgtgac tgagccaggg cctgcatttt
tggttttccc caccccacac 1980attctcaacc atagtccttc taacaatacc aatagctagg
acccggctgc tgtgcactgg 2040gactggggat tccacatgtt tgccttggga gtctcaagct
ggactgccag cccctgtcct 2100cccttcaccc ccattgcgta tgagcatttc agaactccaa
ggagtcacag gcatctttat 2160agttcacgtt aacatataga cactgttgga agcagttcct
tctaaaaggg tagccctgga 2220cttaatacca gccggatacc tctggccccc accccattac
tgtacctctg gagtcactac 2280tgtgggtcgc cactcctctg ctacacagca cggctttttc
aaggctgtat tgagaaggga 2340agttaggaag aagggtgtgc tgggctaacc agcccacaga
gctcacattc ctgtcccttg 2400ggtgaaaaat acatgtccat cctgatatct cctgaattca
gaaattagcc tccacatgtg 2460caatggcttt aagagccaga agcagggttc tgggaatttt
gcaagttacc tgtggccagg 2520tgtggtctcg gttaccaaat acggttacct gcagcttttt
agtcctttgt gctcccacgg 2580gtctacagag tcccatctgc ccaaaggtct tgaagcttga
caggatgttt tcgattactc 2640agtctcccag ggcactactg gtccgtagga ttcgattggt
cggggtagga gagttaaaca 2700acatttaaac agagttctct caaaaatgtc taaagggatt
gtaggtagat aacatccaat 2760cactgtttgc acttatctga aatcttccct cttggctgcc
cccaggtatt tactgtggag 2820aacattgcat aggaatgtct ggaaaaagct tctacaactt
gttacagcct tcacatttgt 2880agaagcttt
2889182089DNAArtificial
SequenceCOX10-opt_ND4-3'UTR* 18atggccgcat ctccgcacac tctctcctca
cgcctcctga caggttgcgt aggaggctct 60gtctggtatc ttgaaagaag aactatgctg
aagctgatcg tgcccaccat catgctgctg 120cctctgacct ggctgagcaa gaaacacatg
atctggatca acaccaccac gcacagcctg 180atcatcagca tcatccctct gctgttcttc
aaccagatca acaacaacct gttcagctgc 240agccccacct tcagcagcga ccctctgaca
acacctctgc tgatgctgac cacctggctg 300ctgcccctca caatcatggc ctctcagaga
cacctgagca gcgagcccct gagccggaag 360aaactgtacc tgagcatgct gatctccctg
cagatctctc tgatcatgac cttcaccgcc 420accgagctga tcatgttcta catctttttc
gagacaacgc tgatccccac actggccatc 480atcaccagat ggggcaacca gcctgagaga
ctgaacgccg gcacctactt tctgttctac 540accctcgtgg gcagcctgcc actgctgatt
gccctgatct acacccacaa caccctgggc 600tccctgaaca tcctgctgct gacactgaca
gcccaagagc tgagcaacag ctgggccaac 660aatctgatgt ggctggccta cacaatggcc
ttcatggtca agatgcccct gtacggcctg 720cacctgtggc tgcctaaagc tcatgtggaa
gcccctatcg ccggctctat ggtgctggct 780gcagtgctgc tgaaactcgg cggctacggc
atgatgcggc tgaccctgat tctgaatccc 840ctgaccaagc acatggccta tccatttctg
gtgctgagcc tgtggggcat gattatgacc 900agcagcatct gcctgcggca gaccgatctg
aagtccctga tcgcctacag ctccatcagc 960cacatggccc tggtggtcac cgccatcctg
attcagaccc cttggagctt tacaggcgcc 1020gtgatcctga tgattgccca cggcctgaca
agcagcctgc tgttttgtct ggccaacagc 1080aactacgagc ggacccacag cagaatcatg
atcctgtctc agggcctgca gaccctcctg 1140cctcttatgg ctttttggtg gctgctggcc
tctctggcca atctggcact gcctcctacc 1200atcaatctgc tgggcgagct gagcgtgctg
gtcaccacat tcagctggtc caatatcacc 1260ctgctgctca ccggcctgaa catgctggtt
acagccctgt actccctgta catgttcacc 1320accacacagt ggggaagcct gacacaccac
atcaacaata tgaagcccag cttcacccgc 1380gagaacaccc tgatgttcat gcatctgagc
cccattctgc tgctgtccct gaatcctgat 1440atcatcaccg gcttctccag ctgagagcac
tgggacgccc accgcccctt tccctccgct 1500gccaggcgag catgttgtgg taattctgga
acacaagaag agaaattgct gggtttagaa 1560caagattata aacgaattcg gtgctcagtg
atcacttgac agtttttttt ttttttaaat 1620attacccaaa atgctcccca aataagaaat
gcatcagctc agtcagtgaa tacaaaaaag 1680gaattatttt tccctttgag ggtcttttat
acatctctcc tccaacccca ccctctattc 1740tgtttcttcc tcctcacatg ggggtacaca
tacacagctt cctcttttgg ttccatcctt 1800accaccacac cacacgcaca ctccacatgc
ccagcagagt ggcacttggt ggccagaaag 1860tgtgagcctc atgatctgct gtctgtagtt
ctgtgagctc aggtccctca aaggcctcgg 1920agcaccccct tccttgtgac tgagccaggg
cctgcatttt tggttttccc caccccacac 1980attctcaacc atagtccttc taacaatacc
aatagctagg acccggctgc tgtgcactgg 2040gactggggat tccacatgtt tgccttggga
gtctcaagct ggactgcca 2089192889DNAArtificial
SequenceCOX10-opt_ND4*-3'UTR 19atggccgcat ctccgcacac tctctcctca
cgcctcctga caggttgcgt aggaggctct 60gtctggtatc ttgaaagaag aactatgctg
aagctgatcg tgcccaccat catgctgctg 120cccctgacct ggctgagcaa gaagcacatg
atctggatca acaccaccac ccacagcctg 180atcatcagca tcatccccct gctgttcttc
aaccagatca acaacaacct gttcagctgc 240agccccacct tcagcagcga ccccctgacc
acccccctgc tgatgctgac cacctggctg 300ctgcccctga ccatcatggc cagccagcgc
cacctgagca gcgagcccct gagccgcaag 360aagctgtacc tgagcatgct gatcagcctg
cagatcagcc tgatcatgac cttcaccgcc 420accgagctga tcatgttcta catcttcttc
gagaccaccc tgatccccac cctggccatc 480atcacccgct ggggcaacca gcccgagcgc
ctgaacgccg gcacctactt cctgttctac 540accctggtgg gcagcctgcc cctgctgatc
gccctgatct acacccacaa caccctgggc 600agcctgaaca tcctgctgct gaccctgacc
gcccaggagc tgagcaacag ctgggccaac 660aacctgatgt ggctggccta caccatggcc
ttcatggtga agatgcccct gtacggcctg 720cacctgtggc tgcccaaggc ccacgtggag
gcccccatcg ccggcagcat ggtgctggcc 780gccgtgctgc tgaagctggg cggctacggc
atgatgcgcc tgaccctgat cctgaacccc 840ctgaccaagc acatggccta ccccttcctg
gtgctgagcc tgtggggcat gatcatgacc 900agcagcatct gcctgcgcca gaccgacctg
aagagcctga tcgcctacag cagcatcagc 960cacatggccc tggtggtgac cgccatcctg
atccagaccc cctggagctt caccggcgcc 1020gtgatcctga tgatcgccca cggcctgacc
agcagcctgc tgttctgcct ggccaacagc 1080aactacgagc gcacccacag ccgcatcatg
atcctgagcc agggcctgca gaccctgctg 1140cccctgatgg ccttctggtg gctgctggcc
agcctggcca acctggccct gccccccacc 1200atcaacctgc tgggcgagct gagcgtgctg
gtgaccacct tcagctggag caacatcacc 1260ctgctgctga ccggcctgaa catgctggtg
accgccctgt acagcctgta catgttcacc 1320accacccagt ggggcagcct gacccaccac
atcaacaaca tgaagcccag cttcacccgc 1380gagaacaccc tgatgttcat gcacctgagc
cccatcctgc tgctgagcct gaaccccgac 1440atcatcaccg gcttcagcag ctaagagcac
tgggacgccc accgcccctt tccctccgct 1500gccaggcgag catgttgtgg taattctgga
acacaagaag agaaattgct gggtttagaa 1560caagattata aacgaattcg gtgctcagtg
atcacttgac agtttttttt ttttttaaat 1620attacccaaa atgctcccca aataagaaat
gcatcagctc agtcagtgaa tacaaaaaag 1680gaattatttt tccctttgag ggtcttttat
acatctctcc tccaacccca ccctctattc 1740tgtttcttcc tcctcacatg ggggtacaca
tacacagctt cctcttttgg ttccatcctt 1800accaccacac cacacgcaca ctccacatgc
ccagcagagt ggcacttggt ggccagaaag 1860tgtgagcctc atgatctgct gtctgtagtt
ctgtgagctc aggtccctca aaggcctcgg 1920agcaccccct tccttgtgac tgagccaggg
cctgcatttt tggttttccc caccccacac 1980attctcaacc atagtccttc taacaatacc
aatagctagg acccggctgc tgtgcactgg 2040gactggggat tccacatgtt tgccttggga
gtctcaagct ggactgccag cccctgtcct 2100cccttcaccc ccattgcgta tgagcatttc
agaactccaa ggagtcacag gcatctttat 2160agttcacgtt aacatataga cactgttgga
agcagttcct tctaaaaggg tagccctgga 2220cttaatacca gccggatacc tctggccccc
accccattac tgtacctctg gagtcactac 2280tgtgggtcgc cactcctctg ctacacagca
cggctttttc aaggctgtat tgagaaggga 2340agttaggaag aagggtgtgc tgggctaacc
agcccacaga gctcacattc ctgtcccttg 2400ggtgaaaaat acatgtccat cctgatatct
cctgaattca gaaattagcc tccacatgtg 2460caatggcttt aagagccaga agcagggttc
tgggaatttt gcaagttacc tgtggccagg 2520tgtggtctcg gttaccaaat acggttacct
gcagcttttt agtcctttgt gctcccacgg 2580gtctacagag tcccatctgc ccaaaggtct
tgaagcttga caggatgttt tcgattactc 2640agtctcccag ggcactactg gtccgtagga
ttcgattggt cggggtagga gagttaaaca 2700acatttaaac agagttctct caaaaatgtc
taaagggatt gtaggtagat aacatccaat 2760cactgtttgc acttatctga aatcttccct
cttggctgcc cccaggtatt tactgtggag 2820aacattgcat aggaatgtct ggaaaaagct
tctacaactt gttacagcct tcacatttgt 2880agaagcttt
2889202089DNAArtificial
SequenceCOX10-opt_ND4*-3'UTR* 20atggccgcat ctccgcacac tctctcctca
cgcctcctga caggttgcgt aggaggctct 60gtctggtatc ttgaaagaag aactatgctg
aagctgatcg tgcccaccat catgctgctg 120cccctgacct ggctgagcaa gaagcacatg
atctggatca acaccaccac ccacagcctg 180atcatcagca tcatccccct gctgttcttc
aaccagatca acaacaacct gttcagctgc 240agccccacct tcagcagcga ccccctgacc
acccccctgc tgatgctgac cacctggctg 300ctgcccctga ccatcatggc cagccagcgc
cacctgagca gcgagcccct gagccgcaag 360aagctgtacc tgagcatgct gatcagcctg
cagatcagcc tgatcatgac cttcaccgcc 420accgagctga tcatgttcta catcttcttc
gagaccaccc tgatccccac cctggccatc 480atcacccgct ggggcaacca gcccgagcgc
ctgaacgccg gcacctactt cctgttctac 540accctggtgg gcagcctgcc cctgctgatc
gccctgatct acacccacaa caccctgggc 600agcctgaaca tcctgctgct gaccctgacc
gcccaggagc tgagcaacag ctgggccaac 660aacctgatgt ggctggccta caccatggcc
ttcatggtga agatgcccct gtacggcctg 720cacctgtggc tgcccaaggc ccacgtggag
gcccccatcg ccggcagcat ggtgctggcc 780gccgtgctgc tgaagctggg cggctacggc
atgatgcgcc tgaccctgat cctgaacccc 840ctgaccaagc acatggccta ccccttcctg
gtgctgagcc tgtggggcat gatcatgacc 900agcagcatct gcctgcgcca gaccgacctg
aagagcctga tcgcctacag cagcatcagc 960cacatggccc tggtggtgac cgccatcctg
atccagaccc cctggagctt caccggcgcc 1020gtgatcctga tgatcgccca cggcctgacc
agcagcctgc tgttctgcct ggccaacagc 1080aactacgagc gcacccacag ccgcatcatg
atcctgagcc agggcctgca gaccctgctg 1140cccctgatgg ccttctggtg gctgctggcc
agcctggcca acctggccct gccccccacc 1200atcaacctgc tgggcgagct gagcgtgctg
gtgaccacct tcagctggag caacatcacc 1260ctgctgctga ccggcctgaa catgctggtg
accgccctgt acagcctgta catgttcacc 1320accacccagt ggggcagcct gacccaccac
atcaacaaca tgaagcccag cttcacccgc 1380gagaacaccc tgatgttcat gcacctgagc
cccatcctgc tgctgagcct gaaccccgac 1440atcatcaccg gcttcagcag ctaagagcac
tgggacgccc accgcccctt tccctccgct 1500gccaggcgag catgttgtgg taattctgga
acacaagaag agaaattgct gggtttagaa 1560caagattata aacgaattcg gtgctcagtg
atcacttgac agtttttttt ttttttaaat 1620attacccaaa atgctcccca aataagaaat
gcatcagctc agtcagtgaa tacaaaaaag 1680gaattatttt tccctttgag ggtcttttat
acatctctcc tccaacccca ccctctattc 1740tgtttcttcc tcctcacatg ggggtacaca
tacacagctt cctcttttgg ttccatcctt 1800accaccacac cacacgcaca ctccacatgc
ccagcagagt ggcacttggt ggccagaaag 1860tgtgagcctc atgatctgct gtctgtagtt
ctgtgagctc aggtccctca aaggcctcgg 1920agcaccccct tccttgtgac tgagccaggg
cctgcatttt tggttttccc caccccacac 1980attctcaacc atagtccttc taacaatacc
aatagctagg acccggctgc tgtgcactgg 2040gactggggat tccacatgtt tgccttggga
gtctcaagct ggactgcca 2089212034DNAArtificial
SequenceCOX10-ND6-3'UTR 21atggccgcat ctccgcacac tctctcctca cgcctcctga
caggttgcgt aggaggctct 60gtctggtatc ttgaaagaag aactatgatg tatgctttgt
ttctgttgag tgtgggttta 120gtaatggggt ttgtggggtt ttcttctaag ccttctccta
tttatggggg tttagtattg 180attgttagcg gtgtggtcgg gtgtgttatt attctgaatt
ttgggggagg ttatatgggt 240ttaatggttt ttttaattta tttaggggga atgatggttg
tctttggata tactacagcg 300atggctattg aggagtatcc tgaggcatgg gggtcagggg
ttgaggtctt ggtgagtgtt 360ttagtggggt tagcgatgga ggtaggattg gtgctgtggg
tgaaagagta tgatggggtg 420gtggttgtgg taaactttaa tagtgtagga agctggatga
tttatgaagg agaggggtca 480gggttgattc gggaggatcc tattggtgcg ggggctttgt
atgattatgg gcgttggtta 540gtagtagtta ctggttggac attgtttgtt ggtgtatata
ttgtaattga gattgctcgg 600gggaattagg agcactggga cgcccaccgc ccctttccct
ccgctgccag gcgagcatgt 660tgtggtaatt ctggaacaca agaagagaaa ttgctgggtt
tagaacaaga ttataaacga 720attcggtgct cagtgatcac ttgacagttt tttttttttt
taaatattac ccaaaatgct 780ccccaaataa gaaatgcatc agctcagtca gtgaatacaa
aaaaggaatt atttttccct 840ttgagggtct tttatacatc tctcctccaa ccccaccctc
tattctgttt cttcctcctc 900acatgggggt acacatacac agcttcctct tttggttcca
tccttaccac cacaccacac 960gcacactcca catgcccagc agagtggcac ttggtggcca
gaaagtgtga gcctcatgat 1020ctgctgtctg tagttctgtg agctcaggtc cctcaaaggc
ctcggagcac ccccttcctt 1080gtgactgagc cagggcctgc atttttggtt ttccccaccc
cacacattct caaccatagt 1140ccttctaaca ataccaatag ctaggacccg gctgctgtgc
actgggactg gggattccac 1200atgtttgcct tgggagtctc aagctggact gccagcccct
gtcctccctt cacccccatt 1260gcgtatgagc atttcagaac tccaaggagt cacaggcatc
tttatagttc acgttaacat 1320atagacactg ttggaagcag ttccttctaa aagggtagcc
ctggacttaa taccagccgg 1380atacctctgg cccccacccc attactgtac ctctggagtc
actactgtgg gtcgccactc 1440ctctgctaca cagcacggct ttttcaaggc tgtattgaga
agggaagtta ggaagaaggg 1500tgtgctgggc taaccagccc acagagctca cattcctgtc
ccttgggtga aaaatacatg 1560tccatcctga tatctcctga attcagaaat tagcctccac
atgtgcaatg gctttaagag 1620ccagaagcag ggttctggga attttgcaag ttacctgtgg
ccaggtgtgg tctcggttac 1680caaatacggt tacctgcagc tttttagtcc tttgtgctcc
cacgggtcta cagagtccca 1740tctgcccaaa ggtcttgaag cttgacagga tgttttcgat
tactcagtct cccagggcac 1800tactggtccg taggattcga ttggtcgggg taggagagtt
aaacaacatt taaacagagt 1860tctctcaaaa atgtctaaag ggattgtagg tagataacat
ccaatcactg tttgcactta 1920tctgaaatct tccctcttgg ctgcccccag gtatttactg
tggagaacat tgcataggaa 1980tgtctggaaa aagcttctac aacttgttac agccttcaca
tttgtagaag cttt 2034221234DNAArtificial SequenceCOX10-ND6-3'UTR*
22atggccgcat ctccgcacac tctctcctca cgcctcctga caggttgcgt aggaggctct
60gtctggtatc ttgaaagaag aactatgatg tatgctttgt ttctgttgag tgtgggttta
120gtaatggggt ttgtggggtt ttcttctaag ccttctccta tttatggggg tttagtattg
180attgttagcg gtgtggtcgg gtgtgttatt attctgaatt ttgggggagg ttatatgggt
240ttaatggttt ttttaattta tttaggggga atgatggttg tctttggata tactacagcg
300atggctattg aggagtatcc tgaggcatgg gggtcagggg ttgaggtctt ggtgagtgtt
360ttagtggggt tagcgatgga ggtaggattg gtgctgtggg tgaaagagta tgatggggtg
420gtggttgtgg taaactttaa tagtgtagga agctggatga tttatgaagg agaggggtca
480gggttgattc gggaggatcc tattggtgcg ggggctttgt atgattatgg gcgttggtta
540gtagtagtta ctggttggac attgtttgtt ggtgtatata ttgtaattga gattgctcgg
600gggaattagg agcactggga cgcccaccgc ccctttccct ccgctgccag gcgagcatgt
660tgtggtaatt ctggaacaca agaagagaaa ttgctgggtt tagaacaaga ttataaacga
720attcggtgct cagtgatcac ttgacagttt tttttttttt taaatattac ccaaaatgct
780ccccaaataa gaaatgcatc agctcagtca gtgaatacaa aaaaggaatt atttttccct
840ttgagggtct tttatacatc tctcctccaa ccccaccctc tattctgttt cttcctcctc
900acatgggggt acacatacac agcttcctct tttggttcca tccttaccac cacaccacac
960gcacactcca catgcccagc agagtggcac ttggtggcca gaaagtgtga gcctcatgat
1020ctgctgtctg tagttctgtg agctcaggtc cctcaaaggc ctcggagcac ccccttcctt
1080gtgactgagc cagggcctgc atttttggtt ttccccaccc cacacattct caaccatagt
1140ccttctaaca ataccaatag ctaggacccg gctgctgtgc actgggactg gggattccac
1200atgtttgcct tgggagtctc aagctggact gcca
1234232034DNAArtificial SequenceCOX10-opt_ND6-3'UTR 23atggccgcat
ctccgcacac tctctcctca cgcctcctga caggttgcgt aggaggctct 60gtctggtatc
ttgaaagaag aactatgatg tacgccctgt tcctgctgag cgtgggcctg 120gtgatgggct
tcgtgggctt cagcagcaag cccagcccca tctacggcgg cctggtgctg 180atcgtgagcg
gcgtggtggg ctgcgtgatc atcctgaact tcggcggcgg ctacatgggc 240ctgatggtgt
tcctgatcta cctgggcggc atgatggtgg tgttcggcta caccaccgcc 300atggccatcg
aggagtaccc cgaggcctgg ggcagcggcg tggaggtgct ggtgagcgtg 360ctggtgggcc
tggccatgga ggtgggcctg gtgctgtggg tgaaggagta cgacggcgtg 420gtggtggtgg
tgaacttcaa cagcgtgggc agctggatga tctacgaggg cgagggcagc 480ggcctgatcc
gcgaggaccc catcggcgcc ggcgccctgt acgactacgg ccgctggctg 540gtggtggtga
ccggctggac cctgttcgtg ggcgtgtaca tcgtgatcga gatcgcccgc 600ggcaactaag
agcactggga cgcccaccgc ccctttccct ccgctgccag gcgagcatgt 660tgtggtaatt
ctggaacaca agaagagaaa ttgctgggtt tagaacaaga ttataaacga 720attcggtgct
cagtgatcac ttgacagttt tttttttttt taaatattac ccaaaatgct 780ccccaaataa
gaaatgcatc agctcagtca gtgaatacaa aaaaggaatt atttttccct 840ttgagggtct
tttatacatc tctcctccaa ccccaccctc tattctgttt cttcctcctc 900acatgggggt
acacatacac agcttcctct tttggttcca tccttaccac cacaccacac 960gcacactcca
catgcccagc agagtggcac ttggtggcca gaaagtgtga gcctcatgat 1020ctgctgtctg
tagttctgtg agctcaggtc cctcaaaggc ctcggagcac ccccttcctt 1080gtgactgagc
cagggcctgc atttttggtt ttccccaccc cacacattct caaccatagt 1140ccttctaaca
ataccaatag ctaggacccg gctgctgtgc actgggactg gggattccac 1200atgtttgcct
tgggagtctc aagctggact gccagcccct gtcctccctt cacccccatt 1260gcgtatgagc
atttcagaac tccaaggagt cacaggcatc tttatagttc acgttaacat 1320atagacactg
ttggaagcag ttccttctaa aagggtagcc ctggacttaa taccagccgg 1380atacctctgg
cccccacccc attactgtac ctctggagtc actactgtgg gtcgccactc 1440ctctgctaca
cagcacggct ttttcaaggc tgtattgaga agggaagtta ggaagaaggg 1500tgtgctgggc
taaccagccc acagagctca cattcctgtc ccttgggtga aaaatacatg 1560tccatcctga
tatctcctga attcagaaat tagcctccac atgtgcaatg gctttaagag 1620ccagaagcag
ggttctggga attttgcaag ttacctgtgg ccaggtgtgg tctcggttac 1680caaatacggt
tacctgcagc tttttagtcc tttgtgctcc cacgggtcta cagagtccca 1740tctgcccaaa
ggtcttgaag cttgacagga tgttttcgat tactcagtct cccagggcac 1800tactggtccg
taggattcga ttggtcgggg taggagagtt aaacaacatt taaacagagt 1860tctctcaaaa
atgtctaaag ggattgtagg tagataacat ccaatcactg tttgcactta 1920tctgaaatct
tccctcttgg ctgcccccag gtatttactg tggagaacat tgcataggaa 1980tgtctggaaa
aagcttctac aacttgttac agccttcaca tttgtagaag cttt
2034241234DNAArtificial SequenceCOX10-opt_ND6-3'UTR* 24atggccgcat
ctccgcacac tctctcctca cgcctcctga caggttgcgt aggaggctct 60gtctggtatc
ttgaaagaag aactatgatg tacgccctgt tcctgctgag cgtgggcctg 120gtgatgggct
tcgtgggctt cagcagcaag cccagcccca tctacggcgg cctggtgctg 180atcgtgagcg
gcgtggtggg ctgcgtgatc atcctgaact tcggcggcgg ctacatgggc 240ctgatggtgt
tcctgatcta cctgggcggc atgatggtgg tgttcggcta caccaccgcc 300atggccatcg
aggagtaccc cgaggcctgg ggcagcggcg tggaggtgct ggtgagcgtg 360ctggtgggcc
tggccatgga ggtgggcctg gtgctgtggg tgaaggagta cgacggcgtg 420gtggtggtgg
tgaacttcaa cagcgtgggc agctggatga tctacgaggg cgagggcagc 480ggcctgatcc
gcgaggaccc catcggcgcc ggcgccctgt acgactacgg ccgctggctg 540gtggtggtga
ccggctggac cctgttcgtg ggcgtgtaca tcgtgatcga gatcgcccgc 600ggcaactaag
agcactggga cgcccaccgc ccctttccct ccgctgccag gcgagcatgt 660tgtggtaatt
ctggaacaca agaagagaaa ttgctgggtt tagaacaaga ttataaacga 720attcggtgct
cagtgatcac ttgacagttt tttttttttt taaatattac ccaaaatgct 780ccccaaataa
gaaatgcatc agctcagtca gtgaatacaa aaaaggaatt atttttccct 840ttgagggtct
tttatacatc tctcctccaa ccccaccctc tattctgttt cttcctcctc 900acatgggggt
acacatacac agcttcctct tttggttcca tccttaccac cacaccacac 960gcacactcca
catgcccagc agagtggcac ttggtggcca gaaagtgtga gcctcatgat 1020ctgctgtctg
tagttctgtg agctcaggtc cctcaaaggc ctcggagcac ccccttcctt 1080gtgactgagc
cagggcctgc atttttggtt ttccccaccc cacacattct caaccatagt 1140ccttctaaca
ataccaatag ctaggacccg gctgctgtgc actgggactg gggattccac 1200atgtttgcct
tgggagtctc aagctggact gcca
1234252466DNAArtificial SequenceCOX10-ND1-3'UTR 25atggccgcat ctccgcacac
tctctcctca cgcctcctga caggttgcgt aggaggctct 60gtctggtatc ttgaaagaag
aactatgccc atggccaacc tcctactcct cattgtaccc 120attctaatcg caatggcatt
cctaatgctt accgaacgaa aaattctagg ctatatgcaa 180ctacgcaaag gccccaacgt
tgtaggcccc tacgggctac tacaaccctt cgctgacgcc 240atgaaactct tcaccaaaga
gcccctaaaa cccgccacat ctaccatcac cctctacatc 300accgccccga ccttagctct
caccatcgct cttctactat ggacccccct ccccatgccc 360aaccccctgg tcaacctcaa
cctaggcctc ctatttattc tagccacctc tagcctagcc 420gtttactcaa tcctctggtc
agggtgggca tcaaactcaa actacgccct gatcggcgca 480ctgcgagcag tagcccaaac
aatctcatat gaagtcaccc tagccatcat tctactatca 540acattactaa tgagtggctc
ctttaacctc tccaccctta tcacaacaca agaacacctc 600tggttactcc tgccatcatg
gcccttggcc atgatgtggt ttatctccac actagcagag 660accaaccgaa cccccttcga
ccttgccgaa ggggagtccg aactagtctc aggcttcaac 720atcgaatacg ccgcaggccc
cttcgcccta ttcttcatgg ccgaatacac aaacattatt 780atgatgaaca ccctcaccac
tacaatcttc ctaggaacaa catatgacgc actctcccct 840gaactctaca caacatattt
tgtcaccaag accctacttc taacctccct gttcttatgg 900attcgaacag catacccccg
attccgctac gaccaactca tgcacctcct atggaaaaac 960ttcctaccac tcaccctagc
attacttatg tggtatgtct ccatgcccat tacaatctcc 1020agcattcccc ctcaaaccta
agagcactgg gacgcccacc gcccctttcc ctccgctgcc 1080aggcgagcat gttgtggtaa
ttctggaaca caagaagaga aattgctggg tttagaacaa 1140gattataaac gaattcggtg
ctcagtgatc acttgacagt tttttttttt tttaaatatt 1200acccaaaatg ctccccaaat
aagaaatgca tcagctcagt cagtgaatac aaaaaaggaa 1260ttatttttcc ctttgagggt
cttttataca tctctcctcc aaccccaccc tctattctgt 1320ttcttcctcc tcacatgggg
gtacacatac acagcttcct cttttggttc catccttacc 1380accacaccac acgcacactc
cacatgccca gcagagtggc acttggtggc cagaaagtgt 1440gagcctcatg atctgctgtc
tgtagttctg tgagctcagg tccctcaaag gcctcggagc 1500acccccttcc ttgtgactga
gccagggcct gcatttttgg ttttccccac cccacacatt 1560ctcaaccata gtccttctaa
caataccaat agctaggacc cggctgctgt gcactgggac 1620tggggattcc acatgtttgc
cttgggagtc tcaagctgga ctgccagccc ctgtcctccc 1680ttcaccccca ttgcgtatga
gcatttcaga actccaagga gtcacaggca tctttatagt 1740tcacgttaac atatagacac
tgttggaagc agttccttct aaaagggtag ccctggactt 1800aataccagcc ggatacctct
ggcccccacc ccattactgt acctctggag tcactactgt 1860gggtcgccac tcctctgcta
cacagcacgg ctttttcaag gctgtattga gaagggaagt 1920taggaagaag ggtgtgctgg
gctaaccagc ccacagagct cacattcctg tcccttgggt 1980gaaaaataca tgtccatcct
gatatctcct gaattcagaa attagcctcc acatgtgcaa 2040tggctttaag agccagaagc
agggttctgg gaattttgca agttacctgt ggccaggtgt 2100ggtctcggtt accaaatacg
gttacctgca gctttttagt cctttgtgct cccacgggtc 2160tacagagtcc catctgccca
aaggtcttga agcttgacag gatgttttcg attactcagt 2220ctcccagggc actactggtc
cgtaggattc gattggtcgg ggtaggagag ttaaacaaca 2280tttaaacaga gttctctcaa
aaatgtctaa agggattgta ggtagataac atccaatcac 2340tgtttgcact tatctgaaat
cttccctctt ggctgccccc aggtatttac tgtggagaac 2400attgcatagg aatgtctgga
aaaagcttct acaacttgtt acagccttca catttgtaga 2460agcttt
2466261666DNAArtificial
SequenceCOX10-ND1-3'UTR* 26atggccgcat ctccgcacac tctctcctca cgcctcctga
caggttgcgt aggaggctct 60gtctggtatc ttgaaagaag aactatgccc atggccaacc
tcctactcct cattgtaccc 120attctaatcg caatggcatt cctaatgctt accgaacgaa
aaattctagg ctatatgcaa 180ctacgcaaag gccccaacgt tgtaggcccc tacgggctac
tacaaccctt cgctgacgcc 240atgaaactct tcaccaaaga gcccctaaaa cccgccacat
ctaccatcac cctctacatc 300accgccccga ccttagctct caccatcgct cttctactat
ggacccccct ccccatgccc 360aaccccctgg tcaacctcaa cctaggcctc ctatttattc
tagccacctc tagcctagcc 420gtttactcaa tcctctggtc agggtgggca tcaaactcaa
actacgccct gatcggcgca 480ctgcgagcag tagcccaaac aatctcatat gaagtcaccc
tagccatcat tctactatca 540acattactaa tgagtggctc ctttaacctc tccaccctta
tcacaacaca agaacacctc 600tggttactcc tgccatcatg gcccttggcc atgatgtggt
ttatctccac actagcagag 660accaaccgaa cccccttcga ccttgccgaa ggggagtccg
aactagtctc aggcttcaac 720atcgaatacg ccgcaggccc cttcgcccta ttcttcatgg
ccgaatacac aaacattatt 780atgatgaaca ccctcaccac tacaatcttc ctaggaacaa
catatgacgc actctcccct 840gaactctaca caacatattt tgtcaccaag accctacttc
taacctccct gttcttatgg 900attcgaacag catacccccg attccgctac gaccaactca
tgcacctcct atggaaaaac 960ttcctaccac tcaccctagc attacttatg tggtatgtct
ccatgcccat tacaatctcc 1020agcattcccc ctcaaaccta agagcactgg gacgcccacc
gcccctttcc ctccgctgcc 1080aggcgagcat gttgtggtaa ttctggaaca caagaagaga
aattgctggg tttagaacaa 1140gattataaac gaattcggtg ctcagtgatc acttgacagt
tttttttttt tttaaatatt 1200acccaaaatg ctccccaaat aagaaatgca tcagctcagt
cagtgaatac aaaaaaggaa 1260ttatttttcc ctttgagggt cttttataca tctctcctcc
aaccccaccc tctattctgt 1320ttcttcctcc tcacatgggg gtacacatac acagcttcct
cttttggttc catccttacc 1380accacaccac acgcacactc cacatgccca gcagagtggc
acttggtggc cagaaagtgt 1440gagcctcatg atctgctgtc tgtagttctg tgagctcagg
tccctcaaag gcctcggagc 1500acccccttcc ttgtgactga gccagggcct gcatttttgg
ttttccccac cccacacatt 1560ctcaaccata gtccttctaa caataccaat agctaggacc
cggctgctgt gcactgggac 1620tggggattcc acatgtttgc cttgggagtc tcaagctgga
ctgcca 1666272466DNAArtificial
SequenceCOX10-opt_ND1-3'UTR 27atggccgcat ctccgcacac tctctcctca cgcctcctga
caggttgcgt aggaggctct 60gtctggtatc ttgaaagaag aactatgccc atggccaacc
tgctgctgct gatcgtgccc 120atcctgatcg ccatggcctt cctgatgctg accgagcgca
agatcctggg ctacatgcag 180ctgcgcaagg gccccaacgt ggtgggcccc tacggcctgc
tgcagccctt cgccgacgcc 240atgaagctgt tcaccaagga gcccctgaag cccgccacca
gcaccatcac cctgtacatc 300accgccccca ccctggccct gaccatcgcc ctgctgctgt
ggacccccct gcccatgccc 360aaccccctgg tgaacctgaa cctgggcctg ctgttcatcc
tggccaccag cagcctggcc 420gtgtacagca tcctgtggag cggctgggcc agcaacagca
actacgccct gatcggcgcc 480ctgcgcgccg tggcccagac catcagctac gaggtgaccc
tggccatcat cctgctgagc 540accctgctga tgagcggcag cttcaacctg agcaccctga
tcaccaccca ggagcacctg 600tggctgctgc tgcccagctg gcccctggcc atgatgtggt
tcatcagcac cctggccgag 660accaaccgca cccccttcga cctggccgag ggcgagagcg
agctggtgag cggcttcaac 720atcgagtacg ccgccggccc cttcgccctg ttcttcatgg
ccgagtacac caacatcatc 780atgatgaaca ccctgaccac caccatcttc ctgggcacca
cctacgacgc cctgagcccc 840gagctgtaca ccacctactt cgtgaccaag accctgctgc
tgaccagcct gttcctgtgg 900atccgcaccg cctacccccg cttccgctac gaccagctga
tgcacctgct gtggaagaac 960ttcctgcccc tgaccctggc cctgctgatg tggtacgtga
gcatgcccat caccatcagc 1020agcatccccc cccagaccta agagcactgg gacgcccacc
gcccctttcc ctccgctgcc 1080aggcgagcat gttgtggtaa ttctggaaca caagaagaga
aattgctggg tttagaacaa 1140gattataaac gaattcggtg ctcagtgatc acttgacagt
tttttttttt tttaaatatt 1200acccaaaatg ctccccaaat aagaaatgca tcagctcagt
cagtgaatac aaaaaaggaa 1260ttatttttcc ctttgagggt cttttataca tctctcctcc
aaccccaccc tctattctgt 1320ttcttcctcc tcacatgggg gtacacatac acagcttcct
cttttggttc catccttacc 1380accacaccac acgcacactc cacatgccca gcagagtggc
acttggtggc cagaaagtgt 1440gagcctcatg atctgctgtc tgtagttctg tgagctcagg
tccctcaaag gcctcggagc 1500acccccttcc ttgtgactga gccagggcct gcatttttgg
ttttccccac cccacacatt 1560ctcaaccata gtccttctaa caataccaat agctaggacc
cggctgctgt gcactgggac 1620tggggattcc acatgtttgc cttgggagtc tcaagctgga
ctgccagccc ctgtcctccc 1680ttcaccccca ttgcgtatga gcatttcaga actccaagga
gtcacaggca tctttatagt 1740tcacgttaac atatagacac tgttggaagc agttccttct
aaaagggtag ccctggactt 1800aataccagcc ggatacctct ggcccccacc ccattactgt
acctctggag tcactactgt 1860gggtcgccac tcctctgcta cacagcacgg ctttttcaag
gctgtattga gaagggaagt 1920taggaagaag ggtgtgctgg gctaaccagc ccacagagct
cacattcctg tcccttgggt 1980gaaaaataca tgtccatcct gatatctcct gaattcagaa
attagcctcc acatgtgcaa 2040tggctttaag agccagaagc agggttctgg gaattttgca
agttacctgt ggccaggtgt 2100ggtctcggtt accaaatacg gttacctgca gctttttagt
cctttgtgct cccacgggtc 2160tacagagtcc catctgccca aaggtcttga agcttgacag
gatgttttcg attactcagt 2220ctcccagggc actactggtc cgtaggattc gattggtcgg
ggtaggagag ttaaacaaca 2280tttaaacaga gttctctcaa aaatgtctaa agggattgta
ggtagataac atccaatcac 2340tgtttgcact tatctgaaat cttccctctt ggctgccccc
aggtatttac tgtggagaac 2400attgcatagg aatgtctgga aaaagcttct acaacttgtt
acagccttca catttgtaga 2460agcttt
2466281666DNAArtificial
SequenceCOX10-opt_ND1-3'UTR* 28atggccgcat ctccgcacac tctctcctca
cgcctcctga caggttgcgt aggaggctct 60gtctggtatc ttgaaagaag aactatgccc
atggccaacc tgctgctgct gatcgtgccc 120atcctgatcg ccatggcctt cctgatgctg
accgagcgca agatcctggg ctacatgcag 180ctgcgcaagg gccccaacgt ggtgggcccc
tacggcctgc tgcagccctt cgccgacgcc 240atgaagctgt tcaccaagga gcccctgaag
cccgccacca gcaccatcac cctgtacatc 300accgccccca ccctggccct gaccatcgcc
ctgctgctgt ggacccccct gcccatgccc 360aaccccctgg tgaacctgaa cctgggcctg
ctgttcatcc tggccaccag cagcctggcc 420gtgtacagca tcctgtggag cggctgggcc
agcaacagca actacgccct gatcggcgcc 480ctgcgcgccg tggcccagac catcagctac
gaggtgaccc tggccatcat cctgctgagc 540accctgctga tgagcggcag cttcaacctg
agcaccctga tcaccaccca ggagcacctg 600tggctgctgc tgcccagctg gcccctggcc
atgatgtggt tcatcagcac cctggccgag 660accaaccgca cccccttcga cctggccgag
ggcgagagcg agctggtgag cggcttcaac 720atcgagtacg ccgccggccc cttcgccctg
ttcttcatgg ccgagtacac caacatcatc 780atgatgaaca ccctgaccac caccatcttc
ctgggcacca cctacgacgc cctgagcccc 840gagctgtaca ccacctactt cgtgaccaag
accctgctgc tgaccagcct gttcctgtgg 900atccgcaccg cctacccccg cttccgctac
gaccagctga tgcacctgct gtggaagaac 960ttcctgcccc tgaccctggc cctgctgatg
tggtacgtga gcatgcccat caccatcagc 1020agcatccccc cccagaccta agagcactgg
gacgcccacc gcccctttcc ctccgctgcc 1080aggcgagcat gttgtggtaa ttctggaaca
caagaagaga aattgctggg tttagaacaa 1140gattataaac gaattcggtg ctcagtgatc
acttgacagt tttttttttt tttaaatatt 1200acccaaaatg ctccccaaat aagaaatgca
tcagctcagt cagtgaatac aaaaaaggaa 1260ttatttttcc ctttgagggt cttttataca
tctctcctcc aaccccaccc tctattctgt 1320ttcttcctcc tcacatgggg gtacacatac
acagcttcct cttttggttc catccttacc 1380accacaccac acgcacactc cacatgccca
gcagagtggc acttggtggc cagaaagtgt 1440gagcctcatg atctgctgtc tgtagttctg
tgagctcagg tccctcaaag gcctcggagc 1500acccccttcc ttgtgactga gccagggcct
gcatttttgg ttttccccac cccacacatt 1560ctcaaccata gtccttctaa caataccaat
agctaggacc cggctgctgt gcactgggac 1620tggggattcc acatgtttgc cttgggagtc
tcaagctgga ctgcca 1666292889DNAArtificial
Sequenceopt_COX10-ND4-3'UTR 29atggccgcct ctccacacac actgagtagc agactgctga
ccggctgtgt tggcggctct 60gtgtggtatc tggaacggcg gacaatgcta aaactaatcg
tcccaacaat tatgttacta 120ccactgacat ggctttccaa aaaacacatg atttggatca
acacaaccac ccacagccta 180attattagca tcatccctct actatttttt aaccaaatca
acaacaacct atttagctgt 240tccccaacct tttcctccga ccccctaaca acccccctcc
taatgctaac tacctggctc 300ctacccctca caatcatggc aagccaacgc cacttatcca
gtgaaccact atcacgaaaa 360aaactctacc tctctatgct aatctcccta caaatctcct
taattatgac attcacagcc 420acagaactaa tcatgtttta tatcttcttc gaaaccacac
ttatccccac cttggctatc 480atcacccgat ggggcaacca gccagaacgc ctgaacgcag
gcacatactt cctattctac 540accctagtag gctcccttcc cctactcatc gcactaattt
acactcacaa caccctaggc 600tcactaaaca ttctactact cactctcact gcccaagaac
tatcaaactc ctgggccaac 660aacttaatgt ggctagctta cacaatggct tttatggtaa
agatgcctct ttacggactc 720cacttatggc tccctaaagc ccatgtcgaa gcccccatcg
ctgggtcaat ggtacttgcc 780gcagtactct taaaactagg cggctatggt atgatgcgcc
tcacactcat tctcaacccc 840ctgacaaaac acatggccta ccccttcctt gtactatccc
tatggggcat gattatgaca 900agctccatct gcctacgaca aacagaccta aaatcgctca
ttgcatactc ttcaatcagc 960cacatggccc tcgtagtaac agccattctc atccaaaccc
cctggagctt caccggcgca 1020gtcattctca tgatcgccca cgggcttaca tcctcattac
tattctgcct agcaaactca 1080aactacgaac gcactcacag tcgcatcatg atcctctctc
aaggacttca aactctactc 1140ccactaatgg ctttttggtg gcttctagca agcctcgcta
acctcgcctt accccccact 1200attaacctac tgggagaact ctctgtgcta gtaaccacgt
tctcctggtc aaatatcact 1260ctcctactta caggactcaa catgctagtc acagccctat
actccctcta catgtttacc 1320acaacacaat ggggctcact cacccaccac attaacaaca
tgaaaccctc attcacacga 1380gaaaacaccc tcatgttcat gcacctatcc cccattctcc
tcctatccct caaccccgac 1440atcattaccg ggttttcctc ttaagagcac tgggacgccc
accgcccctt tccctccgct 1500gccaggcgag catgttgtgg taattctgga acacaagaag
agaaattgct gggtttagaa 1560caagattata aacgaattcg gtgctcagtg atcacttgac
agtttttttt ttttttaaat 1620attacccaaa atgctcccca aataagaaat gcatcagctc
agtcagtgaa tacaaaaaag 1680gaattatttt tccctttgag ggtcttttat acatctctcc
tccaacccca ccctctattc 1740tgtttcttcc tcctcacatg ggggtacaca tacacagctt
cctcttttgg ttccatcctt 1800accaccacac cacacgcaca ctccacatgc ccagcagagt
ggcacttggt ggccagaaag 1860tgtgagcctc atgatctgct gtctgtagtt ctgtgagctc
aggtccctca aaggcctcgg 1920agcaccccct tccttgtgac tgagccaggg cctgcatttt
tggttttccc caccccacac 1980attctcaacc atagtccttc taacaatacc aatagctagg
acccggctgc tgtgcactgg 2040gactggggat tccacatgtt tgccttggga gtctcaagct
ggactgccag cccctgtcct 2100cccttcaccc ccattgcgta tgagcatttc agaactccaa
ggagtcacag gcatctttat 2160agttcacgtt aacatataga cactgttgga agcagttcct
tctaaaaggg tagccctgga 2220cttaatacca gccggatacc tctggccccc accccattac
tgtacctctg gagtcactac 2280tgtgggtcgc cactcctctg ctacacagca cggctttttc
aaggctgtat tgagaaggga 2340agttaggaag aagggtgtgc tgggctaacc agcccacaga
gctcacattc ctgtcccttg 2400ggtgaaaaat acatgtccat cctgatatct cctgaattca
gaaattagcc tccacatgtg 2460caatggcttt aagagccaga agcagggttc tgggaatttt
gcaagttacc tgtggccagg 2520tgtggtctcg gttaccaaat acggttacct gcagcttttt
agtcctttgt gctcccacgg 2580gtctacagag tcccatctgc ccaaaggtct tgaagcttga
caggatgttt tcgattactc 2640agtctcccag ggcactactg gtccgtagga ttcgattggt
cggggtagga gagttaaaca 2700acatttaaac agagttctct caaaaatgtc taaagggatt
gtaggtagat aacatccaat 2760cactgtttgc acttatctga aatcttccct cttggctgcc
cccaggtatt tactgtggag 2820aacattgcat aggaatgtct ggaaaaagct tctacaactt
gttacagcct tcacatttgt 2880agaagcttt
2889302089DNAArtificial
Sequenceopt_COX10-ND4-3'UTR* 30atggccgcct ctccacacac actgagtagc
agactgctga ccggctgtgt tggcggctct 60gtgtggtatc tggaacggcg gacaatgcta
aaactaatcg tcccaacaat tatgttacta 120ccactgacat ggctttccaa aaaacacatg
atttggatca acacaaccac ccacagccta 180attattagca tcatccctct actatttttt
aaccaaatca acaacaacct atttagctgt 240tccccaacct tttcctccga ccccctaaca
acccccctcc taatgctaac tacctggctc 300ctacccctca caatcatggc aagccaacgc
cacttatcca gtgaaccact atcacgaaaa 360aaactctacc tctctatgct aatctcccta
caaatctcct taattatgac attcacagcc 420acagaactaa tcatgtttta tatcttcttc
gaaaccacac ttatccccac cttggctatc 480atcacccgat ggggcaacca gccagaacgc
ctgaacgcag gcacatactt cctattctac 540accctagtag gctcccttcc cctactcatc
gcactaattt acactcacaa caccctaggc 600tcactaaaca ttctactact cactctcact
gcccaagaac tatcaaactc ctgggccaac 660aacttaatgt ggctagctta cacaatggct
tttatggtaa agatgcctct ttacggactc 720cacttatggc tccctaaagc ccatgtcgaa
gcccccatcg ctgggtcaat ggtacttgcc 780gcagtactct taaaactagg cggctatggt
atgatgcgcc tcacactcat tctcaacccc 840ctgacaaaac acatggccta ccccttcctt
gtactatccc tatggggcat gattatgaca 900agctccatct gcctacgaca aacagaccta
aaatcgctca ttgcatactc ttcaatcagc 960cacatggccc tcgtagtaac agccattctc
atccaaaccc cctggagctt caccggcgca 1020gtcattctca tgatcgccca cgggcttaca
tcctcattac tattctgcct agcaaactca 1080aactacgaac gcactcacag tcgcatcatg
atcctctctc aaggacttca aactctactc 1140ccactaatgg ctttttggtg gcttctagca
agcctcgcta acctcgcctt accccccact 1200attaacctac tgggagaact ctctgtgcta
gtaaccacgt tctcctggtc aaatatcact 1260ctcctactta caggactcaa catgctagtc
acagccctat actccctcta catgtttacc 1320acaacacaat ggggctcact cacccaccac
attaacaaca tgaaaccctc attcacacga 1380gaaaacaccc tcatgttcat gcacctatcc
cccattctcc tcctatccct caaccccgac 1440atcattaccg ggttttcctc ttaagagcac
tgggacgccc accgcccctt tccctccgct 1500gccaggcgag catgttgtgg taattctgga
acacaagaag agaaattgct gggtttagaa 1560caagattata aacgaattcg gtgctcagtg
atcacttgac agtttttttt ttttttaaat 1620attacccaaa atgctcccca aataagaaat
gcatcagctc agtcagtgaa tacaaaaaag 1680gaattatttt tccctttgag ggtcttttat
acatctctcc tccaacccca ccctctattc 1740tgtttcttcc tcctcacatg ggggtacaca
tacacagctt cctcttttgg ttccatcctt 1800accaccacac cacacgcaca ctccacatgc
ccagcagagt ggcacttggt ggccagaaag 1860tgtgagcctc atgatctgct gtctgtagtt
ctgtgagctc aggtccctca aaggcctcgg 1920agcaccccct tccttgtgac tgagccaggg
cctgcatttt tggttttccc caccccacac 1980attctcaacc atagtccttc taacaatacc
aatagctagg acccggctgc tgtgcactgg 2040gactggggat tccacatgtt tgccttggga
gtctcaagct ggactgcca 2089312889DNAArtificial
Sequenceopt_COX10-opt_ND4-3'UTR 31atggccgcct ctccacacac actgagtagc
agactgctga ccggctgtgt tggcggctct 60gtgtggtatc tggaacggcg gacaatgctg
aagctgatcg tgcccaccat catgctgctg 120cctctgacct ggctgagcaa gaaacacatg
atctggatca acaccaccac gcacagcctg 180atcatcagca tcatccctct gctgttcttc
aaccagatca acaacaacct gttcagctgc 240agccccacct tcagcagcga ccctctgaca
acacctctgc tgatgctgac cacctggctg 300ctgcccctca caatcatggc ctctcagaga
cacctgagca gcgagcccct gagccggaag 360aaactgtacc tgagcatgct gatctccctg
cagatctctc tgatcatgac cttcaccgcc 420accgagctga tcatgttcta catctttttc
gagacaacgc tgatccccac actggccatc 480atcaccagat ggggcaacca gcctgagaga
ctgaacgccg gcacctactt tctgttctac 540accctcgtgg gcagcctgcc actgctgatt
gccctgatct acacccacaa caccctgggc 600tccctgaaca tcctgctgct gacactgaca
gcccaagagc tgagcaacag ctgggccaac 660aatctgatgt ggctggccta cacaatggcc
ttcatggtca agatgcccct gtacggcctg 720cacctgtggc tgcctaaagc tcatgtggaa
gcccctatcg ccggctctat ggtgctggct 780gcagtgctgc tgaaactcgg cggctacggc
atgatgcggc tgaccctgat tctgaatccc 840ctgaccaagc acatggccta tccatttctg
gtgctgagcc tgtggggcat gattatgacc 900agcagcatct gcctgcggca gaccgatctg
aagtccctga tcgcctacag ctccatcagc 960cacatggccc tggtggtcac cgccatcctg
attcagaccc cttggagctt tacaggcgcc 1020gtgatcctga tgattgccca cggcctgaca
agcagcctgc tgttttgtct ggccaacagc 1080aactacgagc ggacccacag cagaatcatg
atcctgtctc agggcctgca gaccctcctg 1140cctcttatgg ctttttggtg gctgctggcc
tctctggcca atctggcact gcctcctacc 1200atcaatctgc tgggcgagct gagcgtgctg
gtcaccacat tcagctggtc caatatcacc 1260ctgctgctca ccggcctgaa catgctggtt
acagccctgt actccctgta catgttcacc 1320accacacagt ggggaagcct gacacaccac
atcaacaata tgaagcccag cttcacccgc 1380gagaacaccc tgatgttcat gcatctgagc
cccattctgc tgctgtccct gaatcctgat 1440atcatcaccg gcttctccag ctgagagcac
tgggacgccc accgcccctt tccctccgct 1500gccaggcgag catgttgtgg taattctgga
acacaagaag agaaattgct gggtttagaa 1560caagattata aacgaattcg gtgctcagtg
atcacttgac agtttttttt ttttttaaat 1620attacccaaa atgctcccca aataagaaat
gcatcagctc agtcagtgaa tacaaaaaag 1680gaattatttt tccctttgag ggtcttttat
acatctctcc tccaacccca ccctctattc 1740tgtttcttcc tcctcacatg ggggtacaca
tacacagctt cctcttttgg ttccatcctt 1800accaccacac cacacgcaca ctccacatgc
ccagcagagt ggcacttggt ggccagaaag 1860tgtgagcctc atgatctgct gtctgtagtt
ctgtgagctc aggtccctca aaggcctcgg 1920agcaccccct tccttgtgac tgagccaggg
cctgcatttt tggttttccc caccccacac 1980attctcaacc atagtccttc taacaatacc
aatagctagg acccggctgc tgtgcactgg 2040gactggggat tccacatgtt tgccttggga
gtctcaagct ggactgccag cccctgtcct 2100cccttcaccc ccattgcgta tgagcatttc
agaactccaa ggagtcacag gcatctttat 2160agttcacgtt aacatataga cactgttgga
agcagttcct tctaaaaggg tagccctgga 2220cttaatacca gccggatacc tctggccccc
accccattac tgtacctctg gagtcactac 2280tgtgggtcgc cactcctctg ctacacagca
cggctttttc aaggctgtat tgagaaggga 2340agttaggaag aagggtgtgc tgggctaacc
agcccacaga gctcacattc ctgtcccttg 2400ggtgaaaaat acatgtccat cctgatatct
cctgaattca gaaattagcc tccacatgtg 2460caatggcttt aagagccaga agcagggttc
tgggaatttt gcaagttacc tgtggccagg 2520tgtggtctcg gttaccaaat acggttacct
gcagcttttt agtcctttgt gctcccacgg 2580gtctacagag tcccatctgc ccaaaggtct
tgaagcttga caggatgttt tcgattactc 2640agtctcccag ggcactactg gtccgtagga
ttcgattggt cggggtagga gagttaaaca 2700acatttaaac agagttctct caaaaatgtc
taaagggatt gtaggtagat aacatccaat 2760cactgtttgc acttatctga aatcttccct
cttggctgcc cccaggtatt tactgtggag 2820aacattgcat aggaatgtct ggaaaaagct
tctacaactt gttacagcct tcacatttgt 2880agaagcttt
2889322089DNAArtificial
Sequenceopt_COX10-opt_ND4-3'UTR* 32atggccgcct ctccacacac actgagtagc
agactgctga ccggctgtgt tggcggctct 60gtgtggtatc tggaacggcg gacaatgctg
aagctgatcg tgcccaccat catgctgctg 120cctctgacct ggctgagcaa gaaacacatg
atctggatca acaccaccac gcacagcctg 180atcatcagca tcatccctct gctgttcttc
aaccagatca acaacaacct gttcagctgc 240agccccacct tcagcagcga ccctctgaca
acacctctgc tgatgctgac cacctggctg 300ctgcccctca caatcatggc ctctcagaga
cacctgagca gcgagcccct gagccggaag 360aaactgtacc tgagcatgct gatctccctg
cagatctctc tgatcatgac cttcaccgcc 420accgagctga tcatgttcta catctttttc
gagacaacgc tgatccccac actggccatc 480atcaccagat ggggcaacca gcctgagaga
ctgaacgccg gcacctactt tctgttctac 540accctcgtgg gcagcctgcc actgctgatt
gccctgatct acacccacaa caccctgggc 600tccctgaaca tcctgctgct gacactgaca
gcccaagagc tgagcaacag ctgggccaac 660aatctgatgt ggctggccta cacaatggcc
ttcatggtca agatgcccct gtacggcctg 720cacctgtggc tgcctaaagc tcatgtggaa
gcccctatcg ccggctctat ggtgctggct 780gcagtgctgc tgaaactcgg cggctacggc
atgatgcggc tgaccctgat tctgaatccc 840ctgaccaagc acatggccta tccatttctg
gtgctgagcc tgtggggcat gattatgacc 900agcagcatct gcctgcggca gaccgatctg
aagtccctga tcgcctacag ctccatcagc 960cacatggccc tggtggtcac cgccatcctg
attcagaccc cttggagctt tacaggcgcc 1020gtgatcctga tgattgccca cggcctgaca
agcagcctgc tgttttgtct ggccaacagc 1080aactacgagc ggacccacag cagaatcatg
atcctgtctc agggcctgca gaccctcctg 1140cctcttatgg ctttttggtg gctgctggcc
tctctggcca atctggcact gcctcctacc 1200atcaatctgc tgggcgagct gagcgtgctg
gtcaccacat tcagctggtc caatatcacc 1260ctgctgctca ccggcctgaa catgctggtt
acagccctgt actccctgta catgttcacc 1320accacacagt ggggaagcct gacacaccac
atcaacaata tgaagcccag cttcacccgc 1380gagaacaccc tgatgttcat gcatctgagc
cccattctgc tgctgtccct gaatcctgat 1440atcatcaccg gcttctccag ctgagagcac
tgggacgccc accgcccctt tccctccgct 1500gccaggcgag catgttgtgg taattctgga
acacaagaag agaaattgct gggtttagaa 1560caagattata aacgaattcg gtgctcagtg
atcacttgac agtttttttt ttttttaaat 1620attacccaaa atgctcccca aataagaaat
gcatcagctc agtcagtgaa tacaaaaaag 1680gaattatttt tccctttgag ggtcttttat
acatctctcc tccaacccca ccctctattc 1740tgtttcttcc tcctcacatg ggggtacaca
tacacagctt cctcttttgg ttccatcctt 1800accaccacac cacacgcaca ctccacatgc
ccagcagagt ggcacttggt ggccagaaag 1860tgtgagcctc atgatctgct gtctgtagtt
ctgtgagctc aggtccctca aaggcctcgg 1920agcaccccct tccttgtgac tgagccaggg
cctgcatttt tggttttccc caccccacac 1980attctcaacc atagtccttc taacaatacc
aatagctagg acccggctgc tgtgcactgg 2040gactggggat tccacatgtt tgccttggga
gtctcaagct ggactgcca 2089332889DNAArtificial
Sequenceopt_COX10-opt_ND4*-3'UTR 33atggccgcct ctccacacac actgagtagc
agactgctga ccggctgtgt tggcggctct 60gtgtggtatc tggaacggcg gacaatgctg
aagctgatcg tgcccaccat catgctgctg 120cccctgacct ggctgagcaa gaagcacatg
atctggatca acaccaccac ccacagcctg 180atcatcagca tcatccccct gctgttcttc
aaccagatca acaacaacct gttcagctgc 240agccccacct tcagcagcga ccccctgacc
acccccctgc tgatgctgac cacctggctg 300ctgcccctga ccatcatggc cagccagcgc
cacctgagca gcgagcccct gagccgcaag 360aagctgtacc tgagcatgct gatcagcctg
cagatcagcc tgatcatgac cttcaccgcc 420accgagctga tcatgttcta catcttcttc
gagaccaccc tgatccccac cctggccatc 480atcacccgct ggggcaacca gcccgagcgc
ctgaacgccg gcacctactt cctgttctac 540accctggtgg gcagcctgcc cctgctgatc
gccctgatct acacccacaa caccctgggc 600agcctgaaca tcctgctgct gaccctgacc
gcccaggagc tgagcaacag ctgggccaac 660aacctgatgt ggctggccta caccatggcc
ttcatggtga agatgcccct gtacggcctg 720cacctgtggc tgcccaaggc ccacgtggag
gcccccatcg ccggcagcat ggtgctggcc 780gccgtgctgc tgaagctggg cggctacggc
atgatgcgcc tgaccctgat cctgaacccc 840ctgaccaagc acatggccta ccccttcctg
gtgctgagcc tgtggggcat gatcatgacc 900agcagcatct gcctgcgcca gaccgacctg
aagagcctga tcgcctacag cagcatcagc 960cacatggccc tggtggtgac cgccatcctg
atccagaccc cctggagctt caccggcgcc 1020gtgatcctga tgatcgccca cggcctgacc
agcagcctgc tgttctgcct ggccaacagc 1080aactacgagc gcacccacag ccgcatcatg
atcctgagcc agggcctgca gaccctgctg 1140cccctgatgg ccttctggtg gctgctggcc
agcctggcca acctggccct gccccccacc 1200atcaacctgc tgggcgagct gagcgtgctg
gtgaccacct tcagctggag caacatcacc 1260ctgctgctga ccggcctgaa catgctggtg
accgccctgt acagcctgta catgttcacc 1320accacccagt ggggcagcct gacccaccac
atcaacaaca tgaagcccag cttcacccgc 1380gagaacaccc tgatgttcat gcacctgagc
cccatcctgc tgctgagcct gaaccccgac 1440atcatcaccg gcttcagcag ctaagagcac
tgggacgccc accgcccctt tccctccgct 1500gccaggcgag catgttgtgg taattctgga
acacaagaag agaaattgct gggtttagaa 1560caagattata aacgaattcg gtgctcagtg
atcacttgac agtttttttt ttttttaaat 1620attacccaaa atgctcccca aataagaaat
gcatcagctc agtcagtgaa tacaaaaaag 1680gaattatttt tccctttgag ggtcttttat
acatctctcc tccaacccca ccctctattc 1740tgtttcttcc tcctcacatg ggggtacaca
tacacagctt cctcttttgg ttccatcctt 1800accaccacac cacacgcaca ctccacatgc
ccagcagagt ggcacttggt ggccagaaag 1860tgtgagcctc atgatctgct gtctgtagtt
ctgtgagctc aggtccctca aaggcctcgg 1920agcaccccct tccttgtgac tgagccaggg
cctgcatttt tggttttccc caccccacac 1980attctcaacc atagtccttc taacaatacc
aatagctagg acccggctgc tgtgcactgg 2040gactggggat tccacatgtt tgccttggga
gtctcaagct ggactgccag cccctgtcct 2100cccttcaccc ccattgcgta tgagcatttc
agaactccaa ggagtcacag gcatctttat 2160agttcacgtt aacatataga cactgttgga
agcagttcct tctaaaaggg tagccctgga 2220cttaatacca gccggatacc tctggccccc
accccattac tgtacctctg gagtcactac 2280tgtgggtcgc cactcctctg ctacacagca
cggctttttc aaggctgtat tgagaaggga 2340agttaggaag aagggtgtgc tgggctaacc
agcccacaga gctcacattc ctgtcccttg 2400ggtgaaaaat acatgtccat cctgatatct
cctgaattca gaaattagcc tccacatgtg 2460caatggcttt aagagccaga agcagggttc
tgggaatttt gcaagttacc tgtggccagg 2520tgtggtctcg gttaccaaat acggttacct
gcagcttttt agtcctttgt gctcccacgg 2580gtctacagag tcccatctgc ccaaaggtct
tgaagcttga caggatgttt tcgattactc 2640agtctcccag ggcactactg gtccgtagga
ttcgattggt cggggtagga gagttaaaca 2700acatttaaac agagttctct caaaaatgtc
taaagggatt gtaggtagat aacatccaat 2760cactgtttgc acttatctga aatcttccct
cttggctgcc cccaggtatt tactgtggag 2820aacattgcat aggaatgtct ggaaaaagct
tctacaactt gttacagcct tcacatttgt 2880agaagcttt
2889342089DNAArtificial
Sequenceopt_COX10-opt_ND4*-3'UTR* 34atggccgcct ctccacacac actgagtagc
agactgctga ccggctgtgt tggcggctct 60gtgtggtatc tggaacggcg gacaatgctg
aagctgatcg tgcccaccat catgctgctg 120cccctgacct ggctgagcaa gaagcacatg
atctggatca acaccaccac ccacagcctg 180atcatcagca tcatccccct gctgttcttc
aaccagatca acaacaacct gttcagctgc 240agccccacct tcagcagcga ccccctgacc
acccccctgc tgatgctgac cacctggctg 300ctgcccctga ccatcatggc cagccagcgc
cacctgagca gcgagcccct gagccgcaag 360aagctgtacc tgagcatgct gatcagcctg
cagatcagcc tgatcatgac cttcaccgcc 420accgagctga tcatgttcta catcttcttc
gagaccaccc tgatccccac cctggccatc 480atcacccgct ggggcaacca gcccgagcgc
ctgaacgccg gcacctactt cctgttctac 540accctggtgg gcagcctgcc cctgctgatc
gccctgatct acacccacaa caccctgggc 600agcctgaaca tcctgctgct gaccctgacc
gcccaggagc tgagcaacag ctgggccaac 660aacctgatgt ggctggccta caccatggcc
ttcatggtga agatgcccct gtacggcctg 720cacctgtggc tgcccaaggc ccacgtggag
gcccccatcg ccggcagcat ggtgctggcc 780gccgtgctgc tgaagctggg cggctacggc
atgatgcgcc tgaccctgat cctgaacccc 840ctgaccaagc acatggccta ccccttcctg
gtgctgagcc tgtggggcat gatcatgacc 900agcagcatct gcctgcgcca gaccgacctg
aagagcctga tcgcctacag cagcatcagc 960cacatggccc tggtggtgac cgccatcctg
atccagaccc cctggagctt caccggcgcc 1020gtgatcctga tgatcgccca cggcctgacc
agcagcctgc tgttctgcct ggccaacagc 1080aactacgagc gcacccacag ccgcatcatg
atcctgagcc agggcctgca gaccctgctg 1140cccctgatgg ccttctggtg gctgctggcc
agcctggcca acctggccct gccccccacc 1200atcaacctgc tgggcgagct gagcgtgctg
gtgaccacct tcagctggag caacatcacc 1260ctgctgctga ccggcctgaa catgctggtg
accgccctgt acagcctgta catgttcacc 1320accacccagt ggggcagcct gacccaccac
atcaacaaca tgaagcccag cttcacccgc 1380gagaacaccc tgatgttcat gcacctgagc
cccatcctgc tgctgagcct gaaccccgac 1440atcatcaccg gcttcagcag ctaagagcac
tgggacgccc accgcccctt tccctccgct 1500gccaggcgag catgttgtgg taattctgga
acacaagaag agaaattgct gggtttagaa 1560caagattata aacgaattcg gtgctcagtg
atcacttgac agtttttttt ttttttaaat 1620attacccaaa atgctcccca aataagaaat
gcatcagctc agtcagtgaa tacaaaaaag 1680gaattatttt tccctttgag ggtcttttat
acatctctcc tccaacccca ccctctattc 1740tgtttcttcc tcctcacatg ggggtacaca
tacacagctt cctcttttgg ttccatcctt 1800accaccacac cacacgcaca ctccacatgc
ccagcagagt ggcacttggt ggccagaaag 1860tgtgagcctc atgatctgct gtctgtagtt
ctgtgagctc aggtccctca aaggcctcgg 1920agcaccccct tccttgtgac tgagccaggg
cctgcatttt tggttttccc caccccacac 1980attctcaacc atagtccttc taacaatacc
aatagctagg acccggctgc tgtgcactgg 2040gactggggat tccacatgtt tgccttggga
gtctcaagct ggactgcca 2089352034DNAArtificial
Sequenceopt_COX10-ND6-3'UTR 35atggccgcct ctccacacac actgagtagc agactgctga
ccggctgtgt tggcggctct 60gtgtggtatc tggaacggcg gacaatgatg tatgctttgt
ttctgttgag tgtgggttta 120gtaatggggt ttgtggggtt ttcttctaag ccttctccta
tttatggggg tttagtattg 180attgttagcg gtgtggtcgg gtgtgttatt attctgaatt
ttgggggagg ttatatgggt 240ttaatggttt ttttaattta tttaggggga atgatggttg
tctttggata tactacagcg 300atggctattg aggagtatcc tgaggcatgg gggtcagggg
ttgaggtctt ggtgagtgtt 360ttagtggggt tagcgatgga ggtaggattg gtgctgtggg
tgaaagagta tgatggggtg 420gtggttgtgg taaactttaa tagtgtagga agctggatga
tttatgaagg agaggggtca 480gggttgattc gggaggatcc tattggtgcg ggggctttgt
atgattatgg gcgttggtta 540gtagtagtta ctggttggac attgtttgtt ggtgtatata
ttgtaattga gattgctcgg 600gggaattagg agcactggga cgcccaccgc ccctttccct
ccgctgccag gcgagcatgt 660tgtggtaatt ctggaacaca agaagagaaa ttgctgggtt
tagaacaaga ttataaacga 720attcggtgct cagtgatcac ttgacagttt tttttttttt
taaatattac ccaaaatgct 780ccccaaataa gaaatgcatc agctcagtca gtgaatacaa
aaaaggaatt atttttccct 840ttgagggtct tttatacatc tctcctccaa ccccaccctc
tattctgttt cttcctcctc 900acatgggggt acacatacac agcttcctct tttggttcca
tccttaccac cacaccacac 960gcacactcca catgcccagc agagtggcac ttggtggcca
gaaagtgtga gcctcatgat 1020ctgctgtctg tagttctgtg agctcaggtc cctcaaaggc
ctcggagcac ccccttcctt 1080gtgactgagc cagggcctgc atttttggtt ttccccaccc
cacacattct caaccatagt 1140ccttctaaca ataccaatag ctaggacccg gctgctgtgc
actgggactg gggattccac 1200atgtttgcct tgggagtctc aagctggact gccagcccct
gtcctccctt cacccccatt 1260gcgtatgagc atttcagaac tccaaggagt cacaggcatc
tttatagttc acgttaacat 1320atagacactg ttggaagcag ttccttctaa aagggtagcc
ctggacttaa taccagccgg 1380atacctctgg cccccacccc attactgtac ctctggagtc
actactgtgg gtcgccactc 1440ctctgctaca cagcacggct ttttcaaggc tgtattgaga
agggaagtta ggaagaaggg 1500tgtgctgggc taaccagccc acagagctca cattcctgtc
ccttgggtga aaaatacatg 1560tccatcctga tatctcctga attcagaaat tagcctccac
atgtgcaatg gctttaagag 1620ccagaagcag ggttctggga attttgcaag ttacctgtgg
ccaggtgtgg tctcggttac 1680caaatacggt tacctgcagc tttttagtcc tttgtgctcc
cacgggtcta cagagtccca 1740tctgcccaaa ggtcttgaag cttgacagga tgttttcgat
tactcagtct cccagggcac 1800tactggtccg taggattcga ttggtcgggg taggagagtt
aaacaacatt taaacagagt 1860tctctcaaaa atgtctaaag ggattgtagg tagataacat
ccaatcactg tttgcactta 1920tctgaaatct tccctcttgg ctgcccccag gtatttactg
tggagaacat tgcataggaa 1980tgtctggaaa aagcttctac aacttgttac agccttcaca
tttgtagaag cttt 2034361234DNAArtificial
Sequenceopt_COX10-ND6-3'UTR* 36atggccgcct ctccacacac actgagtagc
agactgctga ccggctgtgt tggcggctct 60gtgtggtatc tggaacggcg gacaatgatg
tatgctttgt ttctgttgag tgtgggttta 120gtaatggggt ttgtggggtt ttcttctaag
ccttctccta tttatggggg tttagtattg 180attgttagcg gtgtggtcgg gtgtgttatt
attctgaatt ttgggggagg ttatatgggt 240ttaatggttt ttttaattta tttaggggga
atgatggttg tctttggata tactacagcg 300atggctattg aggagtatcc tgaggcatgg
gggtcagggg ttgaggtctt ggtgagtgtt 360ttagtggggt tagcgatgga ggtaggattg
gtgctgtggg tgaaagagta tgatggggtg 420gtggttgtgg taaactttaa tagtgtagga
agctggatga tttatgaagg agaggggtca 480gggttgattc gggaggatcc tattggtgcg
ggggctttgt atgattatgg gcgttggtta 540gtagtagtta ctggttggac attgtttgtt
ggtgtatata ttgtaattga gattgctcgg 600gggaattagg agcactggga cgcccaccgc
ccctttccct ccgctgccag gcgagcatgt 660tgtggtaatt ctggaacaca agaagagaaa
ttgctgggtt tagaacaaga ttataaacga 720attcggtgct cagtgatcac ttgacagttt
tttttttttt taaatattac ccaaaatgct 780ccccaaataa gaaatgcatc agctcagtca
gtgaatacaa aaaaggaatt atttttccct 840ttgagggtct tttatacatc tctcctccaa
ccccaccctc tattctgttt cttcctcctc 900acatgggggt acacatacac agcttcctct
tttggttcca tccttaccac cacaccacac 960gcacactcca catgcccagc agagtggcac
ttggtggcca gaaagtgtga gcctcatgat 1020ctgctgtctg tagttctgtg agctcaggtc
cctcaaaggc ctcggagcac ccccttcctt 1080gtgactgagc cagggcctgc atttttggtt
ttccccaccc cacacattct caaccatagt 1140ccttctaaca ataccaatag ctaggacccg
gctgctgtgc actgggactg gggattccac 1200atgtttgcct tgggagtctc aagctggact
gcca 1234372034DNAArtificial
Sequenceopt_COX10-opt_ND6-3'UTR 37atggccgcct ctccacacac actgagtagc
agactgctga ccggctgtgt tggcggctct 60gtgtggtatc tggaacggcg gacaatgatg
tacgccctgt tcctgctgag cgtgggcctg 120gtgatgggct tcgtgggctt cagcagcaag
cccagcccca tctacggcgg cctggtgctg 180atcgtgagcg gcgtggtggg ctgcgtgatc
atcctgaact tcggcggcgg ctacatgggc 240ctgatggtgt tcctgatcta cctgggcggc
atgatggtgg tgttcggcta caccaccgcc 300atggccatcg aggagtaccc cgaggcctgg
ggcagcggcg tggaggtgct ggtgagcgtg 360ctggtgggcc tggccatgga ggtgggcctg
gtgctgtggg tgaaggagta cgacggcgtg 420gtggtggtgg tgaacttcaa cagcgtgggc
agctggatga tctacgaggg cgagggcagc 480ggcctgatcc gcgaggaccc catcggcgcc
ggcgccctgt acgactacgg ccgctggctg 540gtggtggtga ccggctggac cctgttcgtg
ggcgtgtaca tcgtgatcga gatcgcccgc 600ggcaactaag agcactggga cgcccaccgc
ccctttccct ccgctgccag gcgagcatgt 660tgtggtaatt ctggaacaca agaagagaaa
ttgctgggtt tagaacaaga ttataaacga 720attcggtgct cagtgatcac ttgacagttt
tttttttttt taaatattac ccaaaatgct 780ccccaaataa gaaatgcatc agctcagtca
gtgaatacaa aaaaggaatt atttttccct 840ttgagggtct tttatacatc tctcctccaa
ccccaccctc tattctgttt cttcctcctc 900acatgggggt acacatacac agcttcctct
tttggttcca tccttaccac cacaccacac 960gcacactcca catgcccagc agagtggcac
ttggtggcca gaaagtgtga gcctcatgat 1020ctgctgtctg tagttctgtg agctcaggtc
cctcaaaggc ctcggagcac ccccttcctt 1080gtgactgagc cagggcctgc atttttggtt
ttccccaccc cacacattct caaccatagt 1140ccttctaaca ataccaatag ctaggacccg
gctgctgtgc actgggactg gggattccac 1200atgtttgcct tgggagtctc aagctggact
gccagcccct gtcctccctt cacccccatt 1260gcgtatgagc atttcagaac tccaaggagt
cacaggcatc tttatagttc acgttaacat 1320atagacactg ttggaagcag ttccttctaa
aagggtagcc ctggacttaa taccagccgg 1380atacctctgg cccccacccc attactgtac
ctctggagtc actactgtgg gtcgccactc 1440ctctgctaca cagcacggct ttttcaaggc
tgtattgaga agggaagtta ggaagaaggg 1500tgtgctgggc taaccagccc acagagctca
cattcctgtc ccttgggtga aaaatacatg 1560tccatcctga tatctcctga attcagaaat
tagcctccac atgtgcaatg gctttaagag 1620ccagaagcag ggttctggga attttgcaag
ttacctgtgg ccaggtgtgg tctcggttac 1680caaatacggt tacctgcagc tttttagtcc
tttgtgctcc cacgggtcta cagagtccca 1740tctgcccaaa ggtcttgaag cttgacagga
tgttttcgat tactcagtct cccagggcac 1800tactggtccg taggattcga ttggtcgggg
taggagagtt aaacaacatt taaacagagt 1860tctctcaaaa atgtctaaag ggattgtagg
tagataacat ccaatcactg tttgcactta 1920tctgaaatct tccctcttgg ctgcccccag
gtatttactg tggagaacat tgcataggaa 1980tgtctggaaa aagcttctac aacttgttac
agccttcaca tttgtagaag cttt 2034381234DNAArtificial
Sequenceopt_COX10-opt_ND6-3'UTR* 38atggccgcct ctccacacac actgagtagc
agactgctga ccggctgtgt tggcggctct 60gtgtggtatc tggaacggcg gacaatgatg
tacgccctgt tcctgctgag cgtgggcctg 120gtgatgggct tcgtgggctt cagcagcaag
cccagcccca tctacggcgg cctggtgctg 180atcgtgagcg gcgtggtggg ctgcgtgatc
atcctgaact tcggcggcgg ctacatgggc 240ctgatggtgt tcctgatcta cctgggcggc
atgatggtgg tgttcggcta caccaccgcc 300atggccatcg aggagtaccc cgaggcctgg
ggcagcggcg tggaggtgct ggtgagcgtg 360ctggtgggcc tggccatgga ggtgggcctg
gtgctgtggg tgaaggagta cgacggcgtg 420gtggtggtgg tgaacttcaa cagcgtgggc
agctggatga tctacgaggg cgagggcagc 480ggcctgatcc gcgaggaccc catcggcgcc
ggcgccctgt acgactacgg ccgctggctg 540gtggtggtga ccggctggac cctgttcgtg
ggcgtgtaca tcgtgatcga gatcgcccgc 600ggcaactaag agcactggga cgcccaccgc
ccctttccct ccgctgccag gcgagcatgt 660tgtggtaatt ctggaacaca agaagagaaa
ttgctgggtt tagaacaaga ttataaacga 720attcggtgct cagtgatcac ttgacagttt
tttttttttt taaatattac ccaaaatgct 780ccccaaataa gaaatgcatc agctcagtca
gtgaatacaa aaaaggaatt atttttccct 840ttgagggtct tttatacatc tctcctccaa
ccccaccctc tattctgttt cttcctcctc 900acatgggggt acacatacac agcttcctct
tttggttcca tccttaccac cacaccacac 960gcacactcca catgcccagc agagtggcac
ttggtggcca gaaagtgtga gcctcatgat 1020ctgctgtctg tagttctgtg agctcaggtc
cctcaaaggc ctcggagcac ccccttcctt 1080gtgactgagc cagggcctgc atttttggtt
ttccccaccc cacacattct caaccatagt 1140ccttctaaca ataccaatag ctaggacccg
gctgctgtgc actgggactg gggattccac 1200atgtttgcct tgggagtctc aagctggact
gcca 1234392466DNAArtificial
Sequenceopt_COX10-ND1-3'UTR 39atggccgcct ctccacacac actgagtagc agactgctga
ccggctgtgt tggcggctct 60gtgtggtatc tggaacggcg gacaatgccc atggccaacc
tcctactcct cattgtaccc 120attctaatcg caatggcatt cctaatgctt accgaacgaa
aaattctagg ctatatgcaa 180ctacgcaaag gccccaacgt tgtaggcccc tacgggctac
tacaaccctt cgctgacgcc 240atgaaactct tcaccaaaga gcccctaaaa cccgccacat
ctaccatcac cctctacatc 300accgccccga ccttagctct caccatcgct cttctactat
ggacccccct ccccatgccc 360aaccccctgg tcaacctcaa cctaggcctc ctatttattc
tagccacctc tagcctagcc 420gtttactcaa tcctctggtc agggtgggca tcaaactcaa
actacgccct gatcggcgca 480ctgcgagcag tagcccaaac aatctcatat gaagtcaccc
tagccatcat tctactatca 540acattactaa tgagtggctc ctttaacctc tccaccctta
tcacaacaca agaacacctc 600tggttactcc tgccatcatg gcccttggcc atgatgtggt
ttatctccac actagcagag 660accaaccgaa cccccttcga ccttgccgaa ggggagtccg
aactagtctc aggcttcaac 720atcgaatacg ccgcaggccc cttcgcccta ttcttcatgg
ccgaatacac aaacattatt 780atgatgaaca ccctcaccac tacaatcttc ctaggaacaa
catatgacgc actctcccct 840gaactctaca caacatattt tgtcaccaag accctacttc
taacctccct gttcttatgg 900attcgaacag catacccccg attccgctac gaccaactca
tgcacctcct atggaaaaac 960ttcctaccac tcaccctagc attacttatg tggtatgtct
ccatgcccat tacaatctcc 1020agcattcccc ctcaaaccta agagcactgg gacgcccacc
gcccctttcc ctccgctgcc 1080aggcgagcat gttgtggtaa ttctggaaca caagaagaga
aattgctggg tttagaacaa 1140gattataaac gaattcggtg ctcagtgatc acttgacagt
tttttttttt tttaaatatt 1200acccaaaatg ctccccaaat aagaaatgca tcagctcagt
cagtgaatac aaaaaaggaa 1260ttatttttcc ctttgagggt cttttataca tctctcctcc
aaccccaccc tctattctgt 1320ttcttcctcc tcacatgggg gtacacatac acagcttcct
cttttggttc catccttacc 1380accacaccac acgcacactc cacatgccca gcagagtggc
acttggtggc cagaaagtgt 1440gagcctcatg atctgctgtc tgtagttctg tgagctcagg
tccctcaaag gcctcggagc 1500acccccttcc ttgtgactga gccagggcct gcatttttgg
ttttccccac cccacacatt 1560ctcaaccata gtccttctaa caataccaat agctaggacc
cggctgctgt gcactgggac 1620tggggattcc acatgtttgc cttgggagtc tcaagctgga
ctgccagccc ctgtcctccc 1680ttcaccccca ttgcgtatga gcatttcaga actccaagga
gtcacaggca tctttatagt 1740tcacgttaac atatagacac tgttggaagc agttccttct
aaaagggtag ccctggactt 1800aataccagcc ggatacctct ggcccccacc ccattactgt
acctctggag tcactactgt 1860gggtcgccac tcctctgcta cacagcacgg ctttttcaag
gctgtattga gaagggaagt 1920taggaagaag ggtgtgctgg gctaaccagc ccacagagct
cacattcctg tcccttgggt 1980gaaaaataca tgtccatcct gatatctcct gaattcagaa
attagcctcc acatgtgcaa 2040tggctttaag agccagaagc agggttctgg gaattttgca
agttacctgt ggccaggtgt 2100ggtctcggtt accaaatacg gttacctgca gctttttagt
cctttgtgct cccacgggtc 2160tacagagtcc catctgccca aaggtcttga agcttgacag
gatgttttcg attactcagt 2220ctcccagggc actactggtc cgtaggattc gattggtcgg
ggtaggagag ttaaacaaca 2280tttaaacaga gttctctcaa aaatgtctaa agggattgta
ggtagataac atccaatcac 2340tgtttgcact tatctgaaat cttccctctt ggctgccccc
aggtatttac tgtggagaac 2400attgcatagg aatgtctgga aaaagcttct acaacttgtt
acagccttca catttgtaga 2460agcttt
2466401666DNAArtificial
Sequenceopt_COX10-ND1-3'UTR* 40atggccgcct ctccacacac actgagtagc
agactgctga ccggctgtgt tggcggctct 60gtgtggtatc tggaacggcg gacaatgccc
atggccaacc tcctactcct cattgtaccc 120attctaatcg caatggcatt cctaatgctt
accgaacgaa aaattctagg ctatatgcaa 180ctacgcaaag gccccaacgt tgtaggcccc
tacgggctac tacaaccctt cgctgacgcc 240atgaaactct tcaccaaaga gcccctaaaa
cccgccacat ctaccatcac cctctacatc 300accgccccga ccttagctct caccatcgct
cttctactat ggacccccct ccccatgccc 360aaccccctgg tcaacctcaa cctaggcctc
ctatttattc tagccacctc tagcctagcc 420gtttactcaa tcctctggtc agggtgggca
tcaaactcaa actacgccct gatcggcgca 480ctgcgagcag tagcccaaac aatctcatat
gaagtcaccc tagccatcat tctactatca 540acattactaa tgagtggctc ctttaacctc
tccaccctta tcacaacaca agaacacctc 600tggttactcc tgccatcatg gcccttggcc
atgatgtggt ttatctccac actagcagag 660accaaccgaa cccccttcga ccttgccgaa
ggggagtccg aactagtctc aggcttcaac 720atcgaatacg ccgcaggccc cttcgcccta
ttcttcatgg ccgaatacac aaacattatt 780atgatgaaca ccctcaccac tacaatcttc
ctaggaacaa catatgacgc actctcccct 840gaactctaca caacatattt tgtcaccaag
accctacttc taacctccct gttcttatgg 900attcgaacag catacccccg attccgctac
gaccaactca tgcacctcct atggaaaaac 960ttcctaccac tcaccctagc attacttatg
tggtatgtct ccatgcccat tacaatctcc 1020agcattcccc ctcaaaccta agagcactgg
gacgcccacc gcccctttcc ctccgctgcc 1080aggcgagcat gttgtggtaa ttctggaaca
caagaagaga aattgctggg tttagaacaa 1140gattataaac gaattcggtg ctcagtgatc
acttgacagt tttttttttt tttaaatatt 1200acccaaaatg ctccccaaat aagaaatgca
tcagctcagt cagtgaatac aaaaaaggaa 1260ttatttttcc ctttgagggt cttttataca
tctctcctcc aaccccaccc tctattctgt 1320ttcttcctcc tcacatgggg gtacacatac
acagcttcct cttttggttc catccttacc 1380accacaccac acgcacactc cacatgccca
gcagagtggc acttggtggc cagaaagtgt 1440gagcctcatg atctgctgtc tgtagttctg
tgagctcagg tccctcaaag gcctcggagc 1500acccccttcc ttgtgactga gccagggcct
gcatttttgg ttttccccac cccacacatt 1560ctcaaccata gtccttctaa caataccaat
agctaggacc cggctgctgt gcactgggac 1620tggggattcc acatgtttgc cttgggagtc
tcaagctgga ctgcca 1666412466DNAArtificial
Sequenceopt_COX10-opt_ND1-3'UTR 41atggccgcct ctccacacac actgagtagc
agactgctga ccggctgtgt tggcggctct 60gtgtggtatc tggaacggcg gacaatgccc
atggccaacc tgctgctgct gatcgtgccc 120atcctgatcg ccatggcctt cctgatgctg
accgagcgca agatcctggg ctacatgcag 180ctgcgcaagg gccccaacgt ggtgggcccc
tacggcctgc tgcagccctt cgccgacgcc 240atgaagctgt tcaccaagga gcccctgaag
cccgccacca gcaccatcac cctgtacatc 300accgccccca ccctggccct gaccatcgcc
ctgctgctgt ggacccccct gcccatgccc 360aaccccctgg tgaacctgaa cctgggcctg
ctgttcatcc tggccaccag cagcctggcc 420gtgtacagca tcctgtggag cggctgggcc
agcaacagca actacgccct gatcggcgcc 480ctgcgcgccg tggcccagac catcagctac
gaggtgaccc tggccatcat cctgctgagc 540accctgctga tgagcggcag cttcaacctg
agcaccctga tcaccaccca ggagcacctg 600tggctgctgc tgcccagctg gcccctggcc
atgatgtggt tcatcagcac cctggccgag 660accaaccgca cccccttcga cctggccgag
ggcgagagcg agctggtgag cggcttcaac 720atcgagtacg ccgccggccc cttcgccctg
ttcttcatgg ccgagtacac caacatcatc 780atgatgaaca ccctgaccac caccatcttc
ctgggcacca cctacgacgc cctgagcccc 840gagctgtaca ccacctactt cgtgaccaag
accctgctgc tgaccagcct gttcctgtgg 900atccgcaccg cctacccccg cttccgctac
gaccagctga tgcacctgct gtggaagaac 960ttcctgcccc tgaccctggc cctgctgatg
tggtacgtga gcatgcccat caccatcagc 1020agcatccccc cccagaccta agagcactgg
gacgcccacc gcccctttcc ctccgctgcc 1080aggcgagcat gttgtggtaa ttctggaaca
caagaagaga aattgctggg tttagaacaa 1140gattataaac gaattcggtg ctcagtgatc
acttgacagt tttttttttt tttaaatatt 1200acccaaaatg ctccccaaat aagaaatgca
tcagctcagt cagtgaatac aaaaaaggaa 1260ttatttttcc ctttgagggt cttttataca
tctctcctcc aaccccaccc tctattctgt 1320ttcttcctcc tcacatgggg gtacacatac
acagcttcct cttttggttc catccttacc 1380accacaccac acgcacactc cacatgccca
gcagagtggc acttggtggc cagaaagtgt 1440gagcctcatg atctgctgtc tgtagttctg
tgagctcagg tccctcaaag gcctcggagc 1500acccccttcc ttgtgactga gccagggcct
gcatttttgg ttttccccac cccacacatt 1560ctcaaccata gtccttctaa caataccaat
agctaggacc cggctgctgt gcactgggac 1620tggggattcc acatgtttgc cttgggagtc
tcaagctgga ctgccagccc ctgtcctccc 1680ttcaccccca ttgcgtatga gcatttcaga
actccaagga gtcacaggca tctttatagt 1740tcacgttaac atatagacac tgttggaagc
agttccttct aaaagggtag ccctggactt 1800aataccagcc ggatacctct ggcccccacc
ccattactgt acctctggag tcactactgt 1860gggtcgccac tcctctgcta cacagcacgg
ctttttcaag gctgtattga gaagggaagt 1920taggaagaag ggtgtgctgg gctaaccagc
ccacagagct cacattcctg tcccttgggt 1980gaaaaataca tgtccatcct gatatctcct
gaattcagaa attagcctcc acatgtgcaa 2040tggctttaag agccagaagc agggttctgg
gaattttgca agttacctgt ggccaggtgt 2100ggtctcggtt accaaatacg gttacctgca
gctttttagt cctttgtgct cccacgggtc 2160tacagagtcc catctgccca aaggtcttga
agcttgacag gatgttttcg attactcagt 2220ctcccagggc actactggtc cgtaggattc
gattggtcgg ggtaggagag ttaaacaaca 2280tttaaacaga gttctctcaa aaatgtctaa
agggattgta ggtagataac atccaatcac 2340tgtttgcact tatctgaaat cttccctctt
ggctgccccc aggtatttac tgtggagaac 2400attgcatagg aatgtctgga aaaagcttct
acaacttgtt acagccttca catttgtaga 2460agcttt
2466421666DNAArtificial
Sequenceopt_COX10-opt_ND1-3'UTR* 42atggccgcct ctccacacac actgagtagc
agactgctga ccggctgtgt tggcggctct 60gtgtggtatc tggaacggcg gacaatgccc
atggccaacc tgctgctgct gatcgtgccc 120atcctgatcg ccatggcctt cctgatgctg
accgagcgca agatcctggg ctacatgcag 180ctgcgcaagg gccccaacgt ggtgggcccc
tacggcctgc tgcagccctt cgccgacgcc 240atgaagctgt tcaccaagga gcccctgaag
cccgccacca gcaccatcac cctgtacatc 300accgccccca ccctggccct gaccatcgcc
ctgctgctgt ggacccccct gcccatgccc 360aaccccctgg tgaacctgaa cctgggcctg
ctgttcatcc tggccaccag cagcctggcc 420gtgtacagca tcctgtggag cggctgggcc
agcaacagca actacgccct gatcggcgcc 480ctgcgcgccg tggcccagac catcagctac
gaggtgaccc tggccatcat cctgctgagc 540accctgctga tgagcggcag cttcaacctg
agcaccctga tcaccaccca ggagcacctg 600tggctgctgc tgcccagctg gcccctggcc
atgatgtggt tcatcagcac cctggccgag 660accaaccgca cccccttcga cctggccgag
ggcgagagcg agctggtgag cggcttcaac 720atcgagtacg ccgccggccc cttcgccctg
ttcttcatgg ccgagtacac caacatcatc 780atgatgaaca ccctgaccac caccatcttc
ctgggcacca cctacgacgc cctgagcccc 840gagctgtaca ccacctactt cgtgaccaag
accctgctgc tgaccagcct gttcctgtgg 900atccgcaccg cctacccccg cttccgctac
gaccagctga tgcacctgct gtggaagaac 960ttcctgcccc tgaccctggc cctgctgatg
tggtacgtga gcatgcccat caccatcagc 1020agcatccccc cccagaccta agagcactgg
gacgcccacc gcccctttcc ctccgctgcc 1080aggcgagcat gttgtggtaa ttctggaaca
caagaagaga aattgctggg tttagaacaa 1140gattataaac gaattcggtg ctcagtgatc
acttgacagt tttttttttt tttaaatatt 1200acccaaaatg ctccccaaat aagaaatgca
tcagctcagt cagtgaatac aaaaaaggaa 1260ttatttttcc ctttgagggt cttttataca
tctctcctcc aaccccaccc tctattctgt 1320ttcttcctcc tcacatgggg gtacacatac
acagcttcct cttttggttc catccttacc 1380accacaccac acgcacactc cacatgccca
gcagagtggc acttggtggc cagaaagtgt 1440gagcctcatg atctgctgtc tgtagttctg
tgagctcagg tccctcaaag gcctcggagc 1500acccccttcc ttgtgactga gccagggcct
gcatttttgg ttttccccac cccacacatt 1560ctcaaccata gtccttctaa caataccaat
agctaggacc cggctgctgt gcactgggac 1620tggggattcc acatgtttgc cttgggagtc
tcaagctgga ctgcca 1666432889DNAArtificial
Sequenceopt_COX10*-ND4-3'UTR 43atggccgcca gcccccacac cctgagcagc
cgcctgctga ccggctgcgt gggcggcagc 60gtgtggtacc tggagcgccg caccatgcta
aaactaatcg tcccaacaat tatgttacta 120ccactgacat ggctttccaa aaaacacatg
atttggatca acacaaccac ccacagccta 180attattagca tcatccctct actatttttt
aaccaaatca acaacaacct atttagctgt 240tccccaacct tttcctccga ccccctaaca
acccccctcc taatgctaac tacctggctc 300ctacccctca caatcatggc aagccaacgc
cacttatcca gtgaaccact atcacgaaaa 360aaactctacc tctctatgct aatctcccta
caaatctcct taattatgac attcacagcc 420acagaactaa tcatgtttta tatcttcttc
gaaaccacac ttatccccac cttggctatc 480atcacccgat ggggcaacca gccagaacgc
ctgaacgcag gcacatactt cctattctac 540accctagtag gctcccttcc cctactcatc
gcactaattt acactcacaa caccctaggc 600tcactaaaca ttctactact cactctcact
gcccaagaac tatcaaactc ctgggccaac 660aacttaatgt ggctagctta cacaatggct
tttatggtaa agatgcctct ttacggactc 720cacttatggc tccctaaagc ccatgtcgaa
gcccccatcg ctgggtcaat ggtacttgcc 780gcagtactct taaaactagg cggctatggt
atgatgcgcc tcacactcat tctcaacccc 840ctgacaaaac acatggccta ccccttcctt
gtactatccc tatggggcat gattatgaca 900agctccatct gcctacgaca aacagaccta
aaatcgctca ttgcatactc ttcaatcagc 960cacatggccc tcgtagtaac agccattctc
atccaaaccc cctggagctt caccggcgca 1020gtcattctca tgatcgccca cgggcttaca
tcctcattac tattctgcct agcaaactca 1080aactacgaac gcactcacag tcgcatcatg
atcctctctc aaggacttca aactctactc 1140ccactaatgg ctttttggtg gcttctagca
agcctcgcta acctcgcctt accccccact 1200attaacctac tgggagaact ctctgtgcta
gtaaccacgt tctcctggtc aaatatcact 1260ctcctactta caggactcaa catgctagtc
acagccctat actccctcta catgtttacc 1320acaacacaat ggggctcact cacccaccac
attaacaaca tgaaaccctc attcacacga 1380gaaaacaccc tcatgttcat gcacctatcc
cccattctcc tcctatccct caaccccgac 1440atcattaccg ggttttcctc ttaagagcac
tgggacgccc accgcccctt tccctccgct 1500gccaggcgag catgttgtgg taattctgga
acacaagaag agaaattgct gggtttagaa 1560caagattata aacgaattcg gtgctcagtg
atcacttgac agtttttttt ttttttaaat 1620attacccaaa atgctcccca aataagaaat
gcatcagctc agtcagtgaa tacaaaaaag 1680gaattatttt tccctttgag ggtcttttat
acatctctcc tccaacccca ccctctattc 1740tgtttcttcc tcctcacatg ggggtacaca
tacacagctt cctcttttgg ttccatcctt 1800accaccacac cacacgcaca ctccacatgc
ccagcagagt ggcacttggt ggccagaaag 1860tgtgagcctc atgatctgct gtctgtagtt
ctgtgagctc aggtccctca aaggcctcgg 1920agcaccccct tccttgtgac tgagccaggg
cctgcatttt tggttttccc caccccacac 1980attctcaacc atagtccttc taacaatacc
aatagctagg acccggctgc tgtgcactgg 2040gactggggat tccacatgtt tgccttggga
gtctcaagct ggactgccag cccctgtcct 2100cccttcaccc ccattgcgta tgagcatttc
agaactccaa ggagtcacag gcatctttat 2160agttcacgtt aacatataga cactgttgga
agcagttcct tctaaaaggg tagccctgga 2220cttaatacca gccggatacc tctggccccc
accccattac tgtacctctg gagtcactac 2280tgtgggtcgc cactcctctg ctacacagca
cggctttttc aaggctgtat tgagaaggga 2340agttaggaag aagggtgtgc tgggctaacc
agcccacaga gctcacattc ctgtcccttg 2400ggtgaaaaat acatgtccat cctgatatct
cctgaattca gaaattagcc tccacatgtg 2460caatggcttt aagagccaga agcagggttc
tgggaatttt gcaagttacc tgtggccagg 2520tgtggtctcg gttaccaaat acggttacct
gcagcttttt agtcctttgt gctcccacgg 2580gtctacagag tcccatctgc ccaaaggtct
tgaagcttga caggatgttt tcgattactc 2640agtctcccag ggcactactg gtccgtagga
ttcgattggt cggggtagga gagttaaaca 2700acatttaaac agagttctct caaaaatgtc
taaagggatt gtaggtagat aacatccaat 2760cactgtttgc acttatctga aatcttccct
cttggctgcc cccaggtatt tactgtggag 2820aacattgcat aggaatgtct ggaaaaagct
tctacaactt gttacagcct tcacatttgt 2880agaagcttt
2889442089DNAArtificial
Sequenceopt_COX10*-ND4-3'UTR* 44atggccgcca gcccccacac cctgagcagc
cgcctgctga ccggctgcgt gggcggcagc 60gtgtggtacc tggagcgccg caccatgcta
aaactaatcg tcccaacaat tatgttacta 120ccactgacat ggctttccaa aaaacacatg
atttggatca acacaaccac ccacagccta 180attattagca tcatccctct actatttttt
aaccaaatca acaacaacct atttagctgt 240tccccaacct tttcctccga ccccctaaca
acccccctcc taatgctaac tacctggctc 300ctacccctca caatcatggc aagccaacgc
cacttatcca gtgaaccact atcacgaaaa 360aaactctacc tctctatgct aatctcccta
caaatctcct taattatgac attcacagcc 420acagaactaa tcatgtttta tatcttcttc
gaaaccacac ttatccccac cttggctatc 480atcacccgat ggggcaacca gccagaacgc
ctgaacgcag gcacatactt cctattctac 540accctagtag gctcccttcc cctactcatc
gcactaattt acactcacaa caccctaggc 600tcactaaaca ttctactact cactctcact
gcccaagaac tatcaaactc ctgggccaac 660aacttaatgt ggctagctta cacaatggct
tttatggtaa agatgcctct ttacggactc 720cacttatggc tccctaaagc ccatgtcgaa
gcccccatcg ctgggtcaat ggtacttgcc 780gcagtactct taaaactagg cggctatggt
atgatgcgcc tcacactcat tctcaacccc 840ctgacaaaac acatggccta ccccttcctt
gtactatccc tatggggcat gattatgaca 900agctccatct gcctacgaca aacagaccta
aaatcgctca ttgcatactc ttcaatcagc 960cacatggccc tcgtagtaac agccattctc
atccaaaccc cctggagctt caccggcgca 1020gtcattctca tgatcgccca cgggcttaca
tcctcattac tattctgcct agcaaactca 1080aactacgaac gcactcacag tcgcatcatg
atcctctctc aaggacttca aactctactc 1140ccactaatgg ctttttggtg gcttctagca
agcctcgcta acctcgcctt accccccact 1200attaacctac tgggagaact ctctgtgcta
gtaaccacgt tctcctggtc aaatatcact 1260ctcctactta caggactcaa catgctagtc
acagccctat actccctcta catgtttacc 1320acaacacaat ggggctcact cacccaccac
attaacaaca tgaaaccctc attcacacga 1380gaaaacaccc tcatgttcat gcacctatcc
cccattctcc tcctatccct caaccccgac 1440atcattaccg ggttttcctc ttaagagcac
tgggacgccc accgcccctt tccctccgct 1500gccaggcgag catgttgtgg taattctgga
acacaagaag agaaattgct gggtttagaa 1560caagattata aacgaattcg gtgctcagtg
atcacttgac agtttttttt ttttttaaat 1620attacccaaa atgctcccca aataagaaat
gcatcagctc agtcagtgaa tacaaaaaag 1680gaattatttt tccctttgag ggtcttttat
acatctctcc tccaacccca ccctctattc 1740tgtttcttcc tcctcacatg ggggtacaca
tacacagctt cctcttttgg ttccatcctt 1800accaccacac cacacgcaca ctccacatgc
ccagcagagt ggcacttggt ggccagaaag 1860tgtgagcctc atgatctgct gtctgtagtt
ctgtgagctc aggtccctca aaggcctcgg 1920agcaccccct tccttgtgac tgagccaggg
cctgcatttt tggttttccc caccccacac 1980attctcaacc atagtccttc taacaatacc
aatagctagg acccggctgc tgtgcactgg 2040gactggggat tccacatgtt tgccttggga
gtctcaagct ggactgcca 2089452889DNAArtificial
Sequenceopt_COX10*-opt_ND4-3'UTR 45atggccgcca gcccccacac cctgagcagc
cgcctgctga ccggctgcgt gggcggcagc 60gtgtggtacc tggagcgccg caccatgctg
aagctgatcg tgcccaccat catgctgctg 120cctctgacct ggctgagcaa gaaacacatg
atctggatca acaccaccac gcacagcctg 180atcatcagca tcatccctct gctgttcttc
aaccagatca acaacaacct gttcagctgc 240agccccacct tcagcagcga ccctctgaca
acacctctgc tgatgctgac cacctggctg 300ctgcccctca caatcatggc ctctcagaga
cacctgagca gcgagcccct gagccggaag 360aaactgtacc tgagcatgct gatctccctg
cagatctctc tgatcatgac cttcaccgcc 420accgagctga tcatgttcta catctttttc
gagacaacgc tgatccccac actggccatc 480atcaccagat ggggcaacca gcctgagaga
ctgaacgccg gcacctactt tctgttctac 540accctcgtgg gcagcctgcc actgctgatt
gccctgatct acacccacaa caccctgggc 600tccctgaaca tcctgctgct gacactgaca
gcccaagagc tgagcaacag ctgggccaac 660aatctgatgt ggctggccta cacaatggcc
ttcatggtca agatgcccct gtacggcctg 720cacctgtggc tgcctaaagc tcatgtggaa
gcccctatcg ccggctctat ggtgctggct 780gcagtgctgc tgaaactcgg cggctacggc
atgatgcggc tgaccctgat tctgaatccc 840ctgaccaagc acatggccta tccatttctg
gtgctgagcc tgtggggcat gattatgacc 900agcagcatct gcctgcggca gaccgatctg
aagtccctga tcgcctacag ctccatcagc 960cacatggccc tggtggtcac cgccatcctg
attcagaccc cttggagctt tacaggcgcc 1020gtgatcctga tgattgccca cggcctgaca
agcagcctgc tgttttgtct ggccaacagc 1080aactacgagc ggacccacag cagaatcatg
atcctgtctc agggcctgca gaccctcctg 1140cctcttatgg ctttttggtg gctgctggcc
tctctggcca atctggcact gcctcctacc 1200atcaatctgc tgggcgagct gagcgtgctg
gtcaccacat tcagctggtc caatatcacc 1260ctgctgctca ccggcctgaa catgctggtt
acagccctgt actccctgta catgttcacc 1320accacacagt ggggaagcct gacacaccac
atcaacaata tgaagcccag cttcacccgc 1380gagaacaccc tgatgttcat gcatctgagc
cccattctgc tgctgtccct gaatcctgat 1440atcatcaccg gcttctccag ctgagagcac
tgggacgccc accgcccctt tccctccgct 1500gccaggcgag catgttgtgg taattctgga
acacaagaag agaaattgct gggtttagaa 1560caagattata aacgaattcg gtgctcagtg
atcacttgac agtttttttt ttttttaaat 1620attacccaaa atgctcccca aataagaaat
gcatcagctc agtcagtgaa tacaaaaaag 1680gaattatttt tccctttgag ggtcttttat
acatctctcc tccaacccca ccctctattc 1740tgtttcttcc tcctcacatg ggggtacaca
tacacagctt cctcttttgg ttccatcctt 1800accaccacac cacacgcaca ctccacatgc
ccagcagagt ggcacttggt ggccagaaag 1860tgtgagcctc atgatctgct gtctgtagtt
ctgtgagctc aggtccctca aaggcctcgg 1920agcaccccct tccttgtgac tgagccaggg
cctgcatttt tggttttccc caccccacac 1980attctcaacc atagtccttc taacaatacc
aatagctagg acccggctgc tgtgcactgg 2040gactggggat tccacatgtt tgccttggga
gtctcaagct ggactgccag cccctgtcct 2100cccttcaccc ccattgcgta tgagcatttc
agaactccaa ggagtcacag gcatctttat 2160agttcacgtt aacatataga cactgttgga
agcagttcct tctaaaaggg tagccctgga 2220cttaatacca gccggatacc tctggccccc
accccattac tgtacctctg gagtcactac 2280tgtgggtcgc cactcctctg ctacacagca
cggctttttc aaggctgtat tgagaaggga 2340agttaggaag aagggtgtgc tgggctaacc
agcccacaga gctcacattc ctgtcccttg 2400ggtgaaaaat acatgtccat cctgatatct
cctgaattca gaaattagcc tccacatgtg 2460caatggcttt aagagccaga agcagggttc
tgggaatttt gcaagttacc tgtggccagg 2520tgtggtctcg gttaccaaat acggttacct
gcagcttttt agtcctttgt gctcccacgg 2580gtctacagag tcccatctgc ccaaaggtct
tgaagcttga caggatgttt tcgattactc 2640agtctcccag ggcactactg gtccgtagga
ttcgattggt cggggtagga gagttaaaca 2700acatttaaac agagttctct caaaaatgtc
taaagggatt gtaggtagat aacatccaat 2760cactgtttgc acttatctga aatcttccct
cttggctgcc cccaggtatt tactgtggag 2820aacattgcat aggaatgtct ggaaaaagct
tctacaactt gttacagcct tcacatttgt 2880agaagcttt
2889462089DNAArtificial
Sequenceopt_COX10*-opt_ND4-3'UTR* 46atggccgcca gcccccacac cctgagcagc
cgcctgctga ccggctgcgt gggcggcagc 60gtgtggtacc tggagcgccg caccatgctg
aagctgatcg tgcccaccat catgctgctg 120cctctgacct ggctgagcaa gaaacacatg
atctggatca acaccaccac gcacagcctg 180atcatcagca tcatccctct gctgttcttc
aaccagatca acaacaacct gttcagctgc 240agccccacct tcagcagcga ccctctgaca
acacctctgc tgatgctgac cacctggctg 300ctgcccctca caatcatggc ctctcagaga
cacctgagca gcgagcccct gagccggaag 360aaactgtacc tgagcatgct gatctccctg
cagatctctc tgatcatgac cttcaccgcc 420accgagctga tcatgttcta catctttttc
gagacaacgc tgatccccac actggccatc 480atcaccagat ggggcaacca gcctgagaga
ctgaacgccg gcacctactt tctgttctac 540accctcgtgg gcagcctgcc actgctgatt
gccctgatct acacccacaa caccctgggc 600tccctgaaca tcctgctgct gacactgaca
gcccaagagc tgagcaacag ctgggccaac 660aatctgatgt ggctggccta cacaatggcc
ttcatggtca agatgcccct gtacggcctg 720cacctgtggc tgcctaaagc tcatgtggaa
gcccctatcg ccggctctat ggtgctggct 780gcagtgctgc tgaaactcgg cggctacggc
atgatgcggc tgaccctgat tctgaatccc 840ctgaccaagc acatggccta tccatttctg
gtgctgagcc tgtggggcat gattatgacc 900agcagcatct gcctgcggca gaccgatctg
aagtccctga tcgcctacag ctccatcagc 960cacatggccc tggtggtcac cgccatcctg
attcagaccc cttggagctt tacaggcgcc 1020gtgatcctga tgattgccca cggcctgaca
agcagcctgc tgttttgtct ggccaacagc 1080aactacgagc ggacccacag cagaatcatg
atcctgtctc agggcctgca gaccctcctg 1140cctcttatgg ctttttggtg gctgctggcc
tctctggcca atctggcact gcctcctacc 1200atcaatctgc tgggcgagct gagcgtgctg
gtcaccacat tcagctggtc caatatcacc 1260ctgctgctca ccggcctgaa catgctggtt
acagccctgt actccctgta catgttcacc 1320accacacagt ggggaagcct gacacaccac
atcaacaata tgaagcccag cttcacccgc 1380gagaacaccc tgatgttcat gcatctgagc
cccattctgc tgctgtccct gaatcctgat 1440atcatcaccg gcttctccag ctgagagcac
tgggacgccc accgcccctt tccctccgct 1500gccaggcgag catgttgtgg taattctgga
acacaagaag agaaattgct gggtttagaa 1560caagattata aacgaattcg gtgctcagtg
atcacttgac agtttttttt ttttttaaat 1620attacccaaa atgctcccca aataagaaat
gcatcagctc agtcagtgaa tacaaaaaag 1680gaattatttt tccctttgag ggtcttttat
acatctctcc tccaacccca ccctctattc 1740tgtttcttcc tcctcacatg ggggtacaca
tacacagctt cctcttttgg ttccatcctt 1800accaccacac cacacgcaca ctccacatgc
ccagcagagt ggcacttggt ggccagaaag 1860tgtgagcctc atgatctgct gtctgtagtt
ctgtgagctc aggtccctca aaggcctcgg 1920agcaccccct tccttgtgac tgagccaggg
cctgcatttt tggttttccc caccccacac 1980attctcaacc atagtccttc taacaatacc
aatagctagg acccggctgc tgtgcactgg 2040gactggggat tccacatgtt tgccttggga
gtctcaagct ggactgcca 2089472889DNAArtificial
Sequenceopt_COX10*-opt_ND4*-3'UTR 47atggccgcca gcccccacac cctgagcagc
cgcctgctga ccggctgcgt gggcggcagc 60gtgtggtacc tggagcgccg caccatgctg
aagctgatcg tgcccaccat catgctgctg 120cccctgacct ggctgagcaa gaagcacatg
atctggatca acaccaccac ccacagcctg 180atcatcagca tcatccccct gctgttcttc
aaccagatca acaacaacct gttcagctgc 240agccccacct tcagcagcga ccccctgacc
acccccctgc tgatgctgac cacctggctg 300ctgcccctga ccatcatggc cagccagcgc
cacctgagca gcgagcccct gagccgcaag 360aagctgtacc tgagcatgct gatcagcctg
cagatcagcc tgatcatgac cttcaccgcc 420accgagctga tcatgttcta catcttcttc
gagaccaccc tgatccccac cctggccatc 480atcacccgct ggggcaacca gcccgagcgc
ctgaacgccg gcacctactt cctgttctac 540accctggtgg gcagcctgcc cctgctgatc
gccctgatct acacccacaa caccctgggc 600agcctgaaca tcctgctgct gaccctgacc
gcccaggagc tgagcaacag ctgggccaac 660aacctgatgt ggctggccta caccatggcc
ttcatggtga agatgcccct gtacggcctg 720cacctgtggc tgcccaaggc ccacgtggag
gcccccatcg ccggcagcat ggtgctggcc 780gccgtgctgc tgaagctggg cggctacggc
atgatgcgcc tgaccctgat cctgaacccc 840ctgaccaagc acatggccta ccccttcctg
gtgctgagcc tgtggggcat gatcatgacc 900agcagcatct gcctgcgcca gaccgacctg
aagagcctga tcgcctacag cagcatcagc 960cacatggccc tggtggtgac cgccatcctg
atccagaccc cctggagctt caccggcgcc 1020gtgatcctga tgatcgccca cggcctgacc
agcagcctgc tgttctgcct ggccaacagc 1080aactacgagc gcacccacag ccgcatcatg
atcctgagcc agggcctgca gaccctgctg 1140cccctgatgg ccttctggtg gctgctggcc
agcctggcca acctggccct gccccccacc 1200atcaacctgc tgggcgagct gagcgtgctg
gtgaccacct tcagctggag caacatcacc 1260ctgctgctga ccggcctgaa catgctggtg
accgccctgt acagcctgta catgttcacc 1320accacccagt ggggcagcct gacccaccac
atcaacaaca tgaagcccag cttcacccgc 1380gagaacaccc tgatgttcat gcacctgagc
cccatcctgc tgctgagcct gaaccccgac 1440atcatcaccg gcttcagcag ctaagagcac
tgggacgccc accgcccctt tccctccgct 1500gccaggcgag catgttgtgg taattctgga
acacaagaag agaaattgct gggtttagaa 1560caagattata aacgaattcg gtgctcagtg
atcacttgac agtttttttt ttttttaaat 1620attacccaaa atgctcccca aataagaaat
gcatcagctc agtcagtgaa tacaaaaaag 1680gaattatttt tccctttgag ggtcttttat
acatctctcc tccaacccca ccctctattc 1740tgtttcttcc tcctcacatg ggggtacaca
tacacagctt cctcttttgg ttccatcctt 1800accaccacac cacacgcaca ctccacatgc
ccagcagagt ggcacttggt ggccagaaag 1860tgtgagcctc atgatctgct gtctgtagtt
ctgtgagctc aggtccctca aaggcctcgg 1920agcaccccct tccttgtgac tgagccaggg
cctgcatttt tggttttccc caccccacac 1980attctcaacc atagtccttc taacaatacc
aatagctagg acccggctgc tgtgcactgg 2040gactggggat tccacatgtt tgccttggga
gtctcaagct ggactgccag cccctgtcct 2100cccttcaccc ccattgcgta tgagcatttc
agaactccaa ggagtcacag gcatctttat 2160agttcacgtt aacatataga cactgttgga
agcagttcct tctaaaaggg tagccctgga 2220cttaatacca gccggatacc tctggccccc
accccattac tgtacctctg gagtcactac 2280tgtgggtcgc cactcctctg ctacacagca
cggctttttc aaggctgtat tgagaaggga 2340agttaggaag aagggtgtgc tgggctaacc
agcccacaga gctcacattc ctgtcccttg 2400ggtgaaaaat acatgtccat cctgatatct
cctgaattca gaaattagcc tccacatgtg 2460caatggcttt aagagccaga agcagggttc
tgggaatttt gcaagttacc tgtggccagg 2520tgtggtctcg gttaccaaat acggttacct
gcagcttttt agtcctttgt gctcccacgg 2580gtctacagag tcccatctgc ccaaaggtct
tgaagcttga caggatgttt tcgattactc 2640agtctcccag ggcactactg gtccgtagga
ttcgattggt cggggtagga gagttaaaca 2700acatttaaac agagttctct caaaaatgtc
taaagggatt gtaggtagat aacatccaat 2760cactgtttgc acttatctga aatcttccct
cttggctgcc cccaggtatt tactgtggag 2820aacattgcat aggaatgtct ggaaaaagct
tctacaactt gttacagcct tcacatttgt 2880agaagcttt
2889482089DNAArtificial
Sequenceopt_COX10*-opt_ND4*-3'UTR* 48atggccgcca gcccccacac cctgagcagc
cgcctgctga ccggctgcgt gggcggcagc 60gtgtggtacc tggagcgccg caccatgctg
aagctgatcg tgcccaccat catgctgctg 120cccctgacct ggctgagcaa gaagcacatg
atctggatca acaccaccac ccacagcctg 180atcatcagca tcatccccct gctgttcttc
aaccagatca acaacaacct gttcagctgc 240agccccacct tcagcagcga ccccctgacc
acccccctgc tgatgctgac cacctggctg 300ctgcccctga ccatcatggc cagccagcgc
cacctgagca gcgagcccct gagccgcaag 360aagctgtacc tgagcatgct gatcagcctg
cagatcagcc tgatcatgac cttcaccgcc 420accgagctga tcatgttcta catcttcttc
gagaccaccc tgatccccac cctggccatc 480atcacccgct ggggcaacca gcccgagcgc
ctgaacgccg gcacctactt cctgttctac 540accctggtgg gcagcctgcc cctgctgatc
gccctgatct acacccacaa caccctgggc 600agcctgaaca tcctgctgct gaccctgacc
gcccaggagc tgagcaacag ctgggccaac 660aacctgatgt ggctggccta caccatggcc
ttcatggtga agatgcccct gtacggcctg 720cacctgtggc tgcccaaggc ccacgtggag
gcccccatcg ccggcagcat ggtgctggcc 780gccgtgctgc tgaagctggg cggctacggc
atgatgcgcc tgaccctgat cctgaacccc 840ctgaccaagc acatggccta ccccttcctg
gtgctgagcc tgtggggcat gatcatgacc 900agcagcatct gcctgcgcca gaccgacctg
aagagcctga tcgcctacag cagcatcagc 960cacatggccc tggtggtgac cgccatcctg
atccagaccc cctggagctt caccggcgcc 1020gtgatcctga tgatcgccca cggcctgacc
agcagcctgc tgttctgcct ggccaacagc 1080aactacgagc gcacccacag ccgcatcatg
atcctgagcc agggcctgca gaccctgctg 1140cccctgatgg ccttctggtg gctgctggcc
agcctggcca acctggccct gccccccacc 1200atcaacctgc tgggcgagct gagcgtgctg
gtgaccacct tcagctggag caacatcacc 1260ctgctgctga ccggcctgaa catgctggtg
accgccctgt acagcctgta catgttcacc 1320accacccagt ggggcagcct gacccaccac
atcaacaaca tgaagcccag cttcacccgc 1380gagaacaccc tgatgttcat gcacctgagc
cccatcctgc tgctgagcct gaaccccgac 1440atcatcaccg gcttcagcag ctaagagcac
tgggacgccc accgcccctt tccctccgct 1500gccaggcgag catgttgtgg taattctgga
acacaagaag agaaattgct gggtttagaa 1560caagattata aacgaattcg gtgctcagtg
atcacttgac agtttttttt ttttttaaat 1620attacccaaa atgctcccca aataagaaat
gcatcagctc agtcagtgaa tacaaaaaag 1680gaattatttt tccctttgag ggtcttttat
acatctctcc tccaacccca ccctctattc 1740tgtttcttcc tcctcacatg ggggtacaca
tacacagctt cctcttttgg ttccatcctt 1800accaccacac cacacgcaca ctccacatgc
ccagcagagt ggcacttggt ggccagaaag 1860tgtgagcctc atgatctgct gtctgtagtt
ctgtgagctc aggtccctca aaggcctcgg 1920agcaccccct tccttgtgac tgagccaggg
cctgcatttt tggttttccc caccccacac 1980attctcaacc atagtccttc taacaatacc
aatagctagg acccggctgc tgtgcactgg 2040gactggggat tccacatgtt tgccttggga
gtctcaagct ggactgcca 2089492034DNAArtificial
Sequenceopt_COX10*-ND6-3'UTR 49atggccgcca gcccccacac cctgagcagc
cgcctgctga ccggctgcgt gggcggcagc 60gtgtggtacc tggagcgccg caccatgatg
tatgctttgt ttctgttgag tgtgggttta 120gtaatggggt ttgtggggtt ttcttctaag
ccttctccta tttatggggg tttagtattg 180attgttagcg gtgtggtcgg gtgtgttatt
attctgaatt ttgggggagg ttatatgggt 240ttaatggttt ttttaattta tttaggggga
atgatggttg tctttggata tactacagcg 300atggctattg aggagtatcc tgaggcatgg
gggtcagggg ttgaggtctt ggtgagtgtt 360ttagtggggt tagcgatgga ggtaggattg
gtgctgtggg tgaaagagta tgatggggtg 420gtggttgtgg taaactttaa tagtgtagga
agctggatga tttatgaagg agaggggtca 480gggttgattc gggaggatcc tattggtgcg
ggggctttgt atgattatgg gcgttggtta 540gtagtagtta ctggttggac attgtttgtt
ggtgtatata ttgtaattga gattgctcgg 600gggaattagg agcactggga cgcccaccgc
ccctttccct ccgctgccag gcgagcatgt 660tgtggtaatt ctggaacaca agaagagaaa
ttgctgggtt tagaacaaga ttataaacga 720attcggtgct cagtgatcac ttgacagttt
tttttttttt taaatattac ccaaaatgct 780ccccaaataa gaaatgcatc agctcagtca
gtgaatacaa aaaaggaatt atttttccct 840ttgagggtct tttatacatc tctcctccaa
ccccaccctc tattctgttt cttcctcctc 900acatgggggt acacatacac agcttcctct
tttggttcca tccttaccac cacaccacac 960gcacactcca catgcccagc agagtggcac
ttggtggcca gaaagtgtga gcctcatgat 1020ctgctgtctg tagttctgtg agctcaggtc
cctcaaaggc ctcggagcac ccccttcctt 1080gtgactgagc cagggcctgc atttttggtt
ttccccaccc cacacattct caaccatagt 1140ccttctaaca ataccaatag ctaggacccg
gctgctgtgc actgggactg gggattccac 1200atgtttgcct tgggagtctc aagctggact
gccagcccct gtcctccctt cacccccatt 1260gcgtatgagc atttcagaac tccaaggagt
cacaggcatc tttatagttc acgttaacat 1320atagacactg ttggaagcag ttccttctaa
aagggtagcc ctggacttaa taccagccgg 1380atacctctgg cccccacccc attactgtac
ctctggagtc actactgtgg gtcgccactc 1440ctctgctaca cagcacggct ttttcaaggc
tgtattgaga agggaagtta ggaagaaggg 1500tgtgctgggc taaccagccc acagagctca
cattcctgtc ccttgggtga aaaatacatg 1560tccatcctga tatctcctga attcagaaat
tagcctccac atgtgcaatg gctttaagag 1620ccagaagcag ggttctggga attttgcaag
ttacctgtgg ccaggtgtgg tctcggttac 1680caaatacggt tacctgcagc tttttagtcc
tttgtgctcc cacgggtcta cagagtccca 1740tctgcccaaa ggtcttgaag cttgacagga
tgttttcgat tactcagtct cccagggcac 1800tactggtccg taggattcga ttggtcgggg
taggagagtt aaacaacatt taaacagagt 1860tctctcaaaa atgtctaaag ggattgtagg
tagataacat ccaatcactg tttgcactta 1920tctgaaatct tccctcttgg ctgcccccag
gtatttactg tggagaacat tgcataggaa 1980tgtctggaaa aagcttctac aacttgttac
agccttcaca tttgtagaag cttt 2034501234DNAArtificial
Sequenceopt_COX10*-ND6-3'UTR* 50atggccgcca gcccccacac cctgagcagc
cgcctgctga ccggctgcgt gggcggcagc 60gtgtggtacc tggagcgccg caccatgatg
tatgctttgt ttctgttgag tgtgggttta 120gtaatggggt ttgtggggtt ttcttctaag
ccttctccta tttatggggg tttagtattg 180attgttagcg gtgtggtcgg gtgtgttatt
attctgaatt ttgggggagg ttatatgggt 240ttaatggttt ttttaattta tttaggggga
atgatggttg tctttggata tactacagcg 300atggctattg aggagtatcc tgaggcatgg
gggtcagggg ttgaggtctt ggtgagtgtt 360ttagtggggt tagcgatgga ggtaggattg
gtgctgtggg tgaaagagta tgatggggtg 420gtggttgtgg taaactttaa tagtgtagga
agctggatga tttatgaagg agaggggtca 480gggttgattc gggaggatcc tattggtgcg
ggggctttgt atgattatgg gcgttggtta 540gtagtagtta ctggttggac attgtttgtt
ggtgtatata ttgtaattga gattgctcgg 600gggaattagg agcactggga cgcccaccgc
ccctttccct ccgctgccag gcgagcatgt 660tgtggtaatt ctggaacaca agaagagaaa
ttgctgggtt tagaacaaga ttataaacga 720attcggtgct cagtgatcac ttgacagttt
tttttttttt taaatattac ccaaaatgct 780ccccaaataa gaaatgcatc agctcagtca
gtgaatacaa aaaaggaatt atttttccct 840ttgagggtct tttatacatc tctcctccaa
ccccaccctc tattctgttt cttcctcctc 900acatgggggt acacatacac agcttcctct
tttggttcca tccttaccac cacaccacac 960gcacactcca catgcccagc agagtggcac
ttggtggcca gaaagtgtga gcctcatgat 1020ctgctgtctg tagttctgtg agctcaggtc
cctcaaaggc ctcggagcac ccccttcctt 1080gtgactgagc cagggcctgc atttttggtt
ttccccaccc cacacattct caaccatagt 1140ccttctaaca ataccaatag ctaggacccg
gctgctgtgc actgggactg gggattccac 1200atgtttgcct tgggagtctc aagctggact
gcca 1234512034DNAArtificial
Sequenceopt_COX10*-opt_ND6-3'UTR 51atggccgcca gcccccacac cctgagcagc
cgcctgctga ccggctgcgt gggcggcagc 60gtgtggtacc tggagcgccg caccatgatg
tacgccctgt tcctgctgag cgtgggcctg 120gtgatgggct tcgtgggctt cagcagcaag
cccagcccca tctacggcgg cctggtgctg 180atcgtgagcg gcgtggtggg ctgcgtgatc
atcctgaact tcggcggcgg ctacatgggc 240ctgatggtgt tcctgatcta cctgggcggc
atgatggtgg tgttcggcta caccaccgcc 300atggccatcg aggagtaccc cgaggcctgg
ggcagcggcg tggaggtgct ggtgagcgtg 360ctggtgggcc tggccatgga ggtgggcctg
gtgctgtggg tgaaggagta cgacggcgtg 420gtggtggtgg tgaacttcaa cagcgtgggc
agctggatga tctacgaggg cgagggcagc 480ggcctgatcc gcgaggaccc catcggcgcc
ggcgccctgt acgactacgg ccgctggctg 540gtggtggtga ccggctggac cctgttcgtg
ggcgtgtaca tcgtgatcga gatcgcccgc 600ggcaactaag agcactggga cgcccaccgc
ccctttccct ccgctgccag gcgagcatgt 660tgtggtaatt ctggaacaca agaagagaaa
ttgctgggtt tagaacaaga ttataaacga 720attcggtgct cagtgatcac ttgacagttt
tttttttttt taaatattac ccaaaatgct 780ccccaaataa gaaatgcatc agctcagtca
gtgaatacaa aaaaggaatt atttttccct 840ttgagggtct tttatacatc tctcctccaa
ccccaccctc tattctgttt cttcctcctc 900acatgggggt acacatacac agcttcctct
tttggttcca tccttaccac cacaccacac 960gcacactcca catgcccagc agagtggcac
ttggtggcca gaaagtgtga gcctcatgat 1020ctgctgtctg tagttctgtg agctcaggtc
cctcaaaggc ctcggagcac ccccttcctt 1080gtgactgagc cagggcctgc atttttggtt
ttccccaccc cacacattct caaccatagt 1140ccttctaaca ataccaatag ctaggacccg
gctgctgtgc actgggactg gggattccac 1200atgtttgcct tgggagtctc aagctggact
gccagcccct gtcctccctt cacccccatt 1260gcgtatgagc atttcagaac tccaaggagt
cacaggcatc tttatagttc acgttaacat 1320atagacactg ttggaagcag ttccttctaa
aagggtagcc ctggacttaa taccagccgg 1380atacctctgg cccccacccc attactgtac
ctctggagtc actactgtgg gtcgccactc 1440ctctgctaca cagcacggct ttttcaaggc
tgtattgaga agggaagtta ggaagaaggg 1500tgtgctgggc taaccagccc acagagctca
cattcctgtc ccttgggtga aaaatacatg 1560tccatcctga tatctcctga attcagaaat
tagcctccac atgtgcaatg gctttaagag 1620ccagaagcag ggttctggga attttgcaag
ttacctgtgg ccaggtgtgg tctcggttac 1680caaatacggt tacctgcagc tttttagtcc
tttgtgctcc cacgggtcta cagagtccca 1740tctgcccaaa ggtcttgaag cttgacagga
tgttttcgat tactcagtct cccagggcac 1800tactggtccg taggattcga ttggtcgggg
taggagagtt aaacaacatt taaacagagt 1860tctctcaaaa atgtctaaag ggattgtagg
tagataacat ccaatcactg tttgcactta 1920tctgaaatct tccctcttgg ctgcccccag
gtatttactg tggagaacat tgcataggaa 1980tgtctggaaa aagcttctac aacttgttac
agccttcaca tttgtagaag cttt 2034521234DNAArtificial
Sequenceopt_COX10*-opt_ND6-3'UTR* 52atggccgcca gcccccacac cctgagcagc
cgcctgctga ccggctgcgt gggcggcagc 60gtgtggtacc tggagcgccg caccatgatg
tacgccctgt tcctgctgag cgtgggcctg 120gtgatgggct tcgtgggctt cagcagcaag
cccagcccca tctacggcgg cctggtgctg 180atcgtgagcg gcgtggtggg ctgcgtgatc
atcctgaact tcggcggcgg ctacatgggc 240ctgatggtgt tcctgatcta cctgggcggc
atgatggtgg tgttcggcta caccaccgcc 300atggccatcg aggagtaccc cgaggcctgg
ggcagcggcg tggaggtgct ggtgagcgtg 360ctggtgggcc tggccatgga ggtgggcctg
gtgctgtggg tgaaggagta cgacggcgtg 420gtggtggtgg tgaacttcaa cagcgtgggc
agctggatga tctacgaggg cgagggcagc 480ggcctgatcc gcgaggaccc catcggcgcc
ggcgccctgt acgactacgg ccgctggctg 540gtggtggtga ccggctggac cctgttcgtg
ggcgtgtaca tcgtgatcga gatcgcccgc 600ggcaactaag agcactggga cgcccaccgc
ccctttccct ccgctgccag gcgagcatgt 660tgtggtaatt ctggaacaca agaagagaaa
ttgctgggtt tagaacaaga ttataaacga 720attcggtgct cagtgatcac ttgacagttt
tttttttttt taaatattac ccaaaatgct 780ccccaaataa gaaatgcatc agctcagtca
gtgaatacaa aaaaggaatt atttttccct 840ttgagggtct tttatacatc tctcctccaa
ccccaccctc tattctgttt cttcctcctc 900acatgggggt acacatacac agcttcctct
tttggttcca tccttaccac cacaccacac 960gcacactcca catgcccagc agagtggcac
ttggtggcca gaaagtgtga gcctcatgat 1020ctgctgtctg tagttctgtg agctcaggtc
cctcaaaggc ctcggagcac ccccttcctt 1080gtgactgagc cagggcctgc atttttggtt
ttccccaccc cacacattct caaccatagt 1140ccttctaaca ataccaatag ctaggacccg
gctgctgtgc actgggactg gggattccac 1200atgtttgcct tgggagtctc aagctggact
gcca 1234532466DNAArtificial
Sequenceopt_COX10*-ND1-3'UTR 53atggccgcca gcccccacac cctgagcagc
cgcctgctga ccggctgcgt gggcggcagc 60gtgtggtacc tggagcgccg caccatgccc
atggccaacc tcctactcct cattgtaccc 120attctaatcg caatggcatt cctaatgctt
accgaacgaa aaattctagg ctatatgcaa 180ctacgcaaag gccccaacgt tgtaggcccc
tacgggctac tacaaccctt cgctgacgcc 240atgaaactct tcaccaaaga gcccctaaaa
cccgccacat ctaccatcac cctctacatc 300accgccccga ccttagctct caccatcgct
cttctactat ggacccccct ccccatgccc 360aaccccctgg tcaacctcaa cctaggcctc
ctatttattc tagccacctc tagcctagcc 420gtttactcaa tcctctggtc agggtgggca
tcaaactcaa actacgccct gatcggcgca 480ctgcgagcag tagcccaaac aatctcatat
gaagtcaccc tagccatcat tctactatca 540acattactaa tgagtggctc ctttaacctc
tccaccctta tcacaacaca agaacacctc 600tggttactcc tgccatcatg gcccttggcc
atgatgtggt ttatctccac actagcagag 660accaaccgaa cccccttcga ccttgccgaa
ggggagtccg aactagtctc aggcttcaac 720atcgaatacg ccgcaggccc cttcgcccta
ttcttcatgg ccgaatacac aaacattatt 780atgatgaaca ccctcaccac tacaatcttc
ctaggaacaa catatgacgc actctcccct 840gaactctaca caacatattt tgtcaccaag
accctacttc taacctccct gttcttatgg 900attcgaacag catacccccg attccgctac
gaccaactca tgcacctcct atggaaaaac 960ttcctaccac tcaccctagc attacttatg
tggtatgtct ccatgcccat tacaatctcc 1020agcattcccc ctcaaaccta agagcactgg
gacgcccacc gcccctttcc ctccgctgcc 1080aggcgagcat gttgtggtaa ttctggaaca
caagaagaga aattgctggg tttagaacaa 1140gattataaac gaattcggtg ctcagtgatc
acttgacagt tttttttttt tttaaatatt 1200acccaaaatg ctccccaaat aagaaatgca
tcagctcagt cagtgaatac aaaaaaggaa 1260ttatttttcc ctttgagggt cttttataca
tctctcctcc aaccccaccc tctattctgt 1320ttcttcctcc tcacatgggg gtacacatac
acagcttcct cttttggttc catccttacc 1380accacaccac acgcacactc cacatgccca
gcagagtggc acttggtggc cagaaagtgt 1440gagcctcatg atctgctgtc tgtagttctg
tgagctcagg tccctcaaag gcctcggagc 1500acccccttcc ttgtgactga gccagggcct
gcatttttgg ttttccccac cccacacatt 1560ctcaaccata gtccttctaa caataccaat
agctaggacc cggctgctgt gcactgggac 1620tggggattcc acatgtttgc cttgggagtc
tcaagctgga ctgccagccc ctgtcctccc 1680ttcaccccca ttgcgtatga gcatttcaga
actccaagga gtcacaggca tctttatagt 1740tcacgttaac atatagacac tgttggaagc
agttccttct aaaagggtag ccctggactt 1800aataccagcc ggatacctct ggcccccacc
ccattactgt acctctggag tcactactgt 1860gggtcgccac tcctctgcta cacagcacgg
ctttttcaag gctgtattga gaagggaagt 1920taggaagaag ggtgtgctgg gctaaccagc
ccacagagct cacattcctg tcccttgggt 1980gaaaaataca tgtccatcct gatatctcct
gaattcagaa attagcctcc acatgtgcaa 2040tggctttaag agccagaagc agggttctgg
gaattttgca agttacctgt ggccaggtgt 2100ggtctcggtt accaaatacg gttacctgca
gctttttagt cctttgtgct cccacgggtc 2160tacagagtcc catctgccca aaggtcttga
agcttgacag gatgttttcg attactcagt 2220ctcccagggc actactggtc cgtaggattc
gattggtcgg ggtaggagag ttaaacaaca 2280tttaaacaga gttctctcaa aaatgtctaa
agggattgta ggtagataac atccaatcac 2340tgtttgcact tatctgaaat cttccctctt
ggctgccccc aggtatttac tgtggagaac 2400attgcatagg aatgtctgga aaaagcttct
acaacttgtt acagccttca catttgtaga 2460agcttt
2466541666DNAArtificial
Sequenceopt_COX10*-ND1-3'UTR* 54atggccgcca gcccccacac cctgagcagc
cgcctgctga ccggctgcgt gggcggcagc 60gtgtggtacc tggagcgccg caccatgccc
atggccaacc tcctactcct cattgtaccc 120attctaatcg caatggcatt cctaatgctt
accgaacgaa aaattctagg ctatatgcaa 180ctacgcaaag gccccaacgt tgtaggcccc
tacgggctac tacaaccctt cgctgacgcc 240atgaaactct tcaccaaaga gcccctaaaa
cccgccacat ctaccatcac cctctacatc 300accgccccga ccttagctct caccatcgct
cttctactat ggacccccct ccccatgccc 360aaccccctgg tcaacctcaa cctaggcctc
ctatttattc tagccacctc tagcctagcc 420gtttactcaa tcctctggtc agggtgggca
tcaaactcaa actacgccct gatcggcgca 480ctgcgagcag tagcccaaac aatctcatat
gaagtcaccc tagccatcat tctactatca 540acattactaa tgagtggctc ctttaacctc
tccaccctta tcacaacaca agaacacctc 600tggttactcc tgccatcatg gcccttggcc
atgatgtggt ttatctccac actagcagag 660accaaccgaa cccccttcga ccttgccgaa
ggggagtccg aactagtctc aggcttcaac 720atcgaatacg ccgcaggccc cttcgcccta
ttcttcatgg ccgaatacac aaacattatt 780atgatgaaca ccctcaccac tacaatcttc
ctaggaacaa catatgacgc actctcccct 840gaactctaca caacatattt tgtcaccaag
accctacttc taacctccct gttcttatgg 900attcgaacag catacccccg attccgctac
gaccaactca tgcacctcct atggaaaaac 960ttcctaccac tcaccctagc attacttatg
tggtatgtct ccatgcccat tacaatctcc 1020agcattcccc ctcaaaccta agagcactgg
gacgcccacc gcccctttcc ctccgctgcc 1080aggcgagcat gttgtggtaa ttctggaaca
caagaagaga aattgctggg tttagaacaa 1140gattataaac gaattcggtg ctcagtgatc
acttgacagt tttttttttt tttaaatatt 1200acccaaaatg ctccccaaat aagaaatgca
tcagctcagt cagtgaatac aaaaaaggaa 1260ttatttttcc ctttgagggt cttttataca
tctctcctcc aaccccaccc tctattctgt 1320ttcttcctcc tcacatgggg gtacacatac
acagcttcct cttttggttc catccttacc 1380accacaccac acgcacactc cacatgccca
gcagagtggc acttggtggc cagaaagtgt 1440gagcctcatg atctgctgtc tgtagttctg
tgagctcagg tccctcaaag gcctcggagc 1500acccccttcc ttgtgactga gccagggcct
gcatttttgg ttttccccac cccacacatt 1560ctcaaccata gtccttctaa caataccaat
agctaggacc cggctgctgt gcactgggac 1620tggggattcc acatgtttgc cttgggagtc
tcaagctgga ctgcca 1666552466DNAArtificial
Sequenceopt_COX10*-opt_ND1-3'UTR 55atggccgcca gcccccacac cctgagcagc
cgcctgctga ccggctgcgt gggcggcagc 60gtgtggtacc tggagcgccg caccatgccc
atggccaacc tgctgctgct gatcgtgccc 120atcctgatcg ccatggcctt cctgatgctg
accgagcgca agatcctggg ctacatgcag 180ctgcgcaagg gccccaacgt ggtgggcccc
tacggcctgc tgcagccctt cgccgacgcc 240atgaagctgt tcaccaagga gcccctgaag
cccgccacca gcaccatcac cctgtacatc 300accgccccca ccctggccct gaccatcgcc
ctgctgctgt ggacccccct gcccatgccc 360aaccccctgg tgaacctgaa cctgggcctg
ctgttcatcc tggccaccag cagcctggcc 420gtgtacagca tcctgtggag cggctgggcc
agcaacagca actacgccct gatcggcgcc 480ctgcgcgccg tggcccagac catcagctac
gaggtgaccc tggccatcat cctgctgagc 540accctgctga tgagcggcag cttcaacctg
agcaccctga tcaccaccca ggagcacctg 600tggctgctgc tgcccagctg gcccctggcc
atgatgtggt tcatcagcac cctggccgag 660accaaccgca cccccttcga cctggccgag
ggcgagagcg agctggtgag cggcttcaac 720atcgagtacg ccgccggccc cttcgccctg
ttcttcatgg ccgagtacac caacatcatc 780atgatgaaca ccctgaccac caccatcttc
ctgggcacca cctacgacgc cctgagcccc 840gagctgtaca ccacctactt cgtgaccaag
accctgctgc tgaccagcct gttcctgtgg 900atccgcaccg cctacccccg cttccgctac
gaccagctga tgcacctgct gtggaagaac 960ttcctgcccc tgaccctggc cctgctgatg
tggtacgtga gcatgcccat caccatcagc 1020agcatccccc cccagaccta agagcactgg
gacgcccacc gcccctttcc ctccgctgcc 1080aggcgagcat gttgtggtaa ttctggaaca
caagaagaga aattgctggg tttagaacaa 1140gattataaac gaattcggtg ctcagtgatc
acttgacagt tttttttttt tttaaatatt 1200acccaaaatg ctccccaaat aagaaatgca
tcagctcagt cagtgaatac aaaaaaggaa 1260ttatttttcc ctttgagggt cttttataca
tctctcctcc aaccccaccc tctattctgt 1320ttcttcctcc tcacatgggg gtacacatac
acagcttcct cttttggttc catccttacc 1380accacaccac acgcacactc cacatgccca
gcagagtggc acttggtggc cagaaagtgt 1440gagcctcatg atctgctgtc tgtagttctg
tgagctcagg tccctcaaag gcctcggagc 1500acccccttcc ttgtgactga gccagggcct
gcatttttgg ttttccccac cccacacatt 1560ctcaaccata gtccttctaa caataccaat
agctaggacc cggctgctgt gcactgggac 1620tggggattcc acatgtttgc cttgggagtc
tcaagctgga ctgccagccc ctgtcctccc 1680ttcaccccca ttgcgtatga gcatttcaga
actccaagga gtcacaggca tctttatagt 1740tcacgttaac atatagacac tgttggaagc
agttccttct aaaagggtag ccctggactt 1800aataccagcc ggatacctct ggcccccacc
ccattactgt acctctggag tcactactgt 1860gggtcgccac tcctctgcta cacagcacgg
ctttttcaag gctgtattga gaagggaagt 1920taggaagaag ggtgtgctgg gctaaccagc
ccacagagct cacattcctg tcccttgggt 1980gaaaaataca tgtccatcct gatatctcct
gaattcagaa attagcctcc acatgtgcaa 2040tggctttaag agccagaagc agggttctgg
gaattttgca agttacctgt ggccaggtgt 2100ggtctcggtt accaaatacg gttacctgca
gctttttagt cctttgtgct cccacgggtc 2160tacagagtcc catctgccca aaggtcttga
agcttgacag gatgttttcg attactcagt 2220ctcccagggc actactggtc cgtaggattc
gattggtcgg ggtaggagag ttaaacaaca 2280tttaaacaga gttctctcaa aaatgtctaa
agggattgta ggtagataac atccaatcac 2340tgtttgcact tatctgaaat cttccctctt
ggctgccccc aggtatttac tgtggagaac 2400attgcatagg aatgtctgga aaaagcttct
acaacttgtt acagccttca catttgtaga 2460agcttt
2466561666DNAArtificial
Sequenceopt_COX10*-opt_ND1-3'UTR* 56atggccgcca gcccccacac cctgagcagc
cgcctgctga ccggctgcgt gggcggcagc 60gtgtggtacc tggagcgccg caccatgccc
atggccaacc tgctgctgct gatcgtgccc 120atcctgatcg ccatggcctt cctgatgctg
accgagcgca agatcctggg ctacatgcag 180ctgcgcaagg gccccaacgt ggtgggcccc
tacggcctgc tgcagccctt cgccgacgcc 240atgaagctgt tcaccaagga gcccctgaag
cccgccacca gcaccatcac cctgtacatc 300accgccccca ccctggccct gaccatcgcc
ctgctgctgt ggacccccct gcccatgccc 360aaccccctgg tgaacctgaa cctgggcctg
ctgttcatcc tggccaccag cagcctggcc 420gtgtacagca tcctgtggag cggctgggcc
agcaacagca actacgccct gatcggcgcc 480ctgcgcgccg tggcccagac catcagctac
gaggtgaccc tggccatcat cctgctgagc 540accctgctga tgagcggcag cttcaacctg
agcaccctga tcaccaccca ggagcacctg 600tggctgctgc tgcccagctg gcccctggcc
atgatgtggt tcatcagcac cctggccgag 660accaaccgca cccccttcga cctggccgag
ggcgagagcg agctggtgag cggcttcaac 720atcgagtacg ccgccggccc cttcgccctg
ttcttcatgg ccgagtacac caacatcatc 780atgatgaaca ccctgaccac caccatcttc
ctgggcacca cctacgacgc cctgagcccc 840gagctgtaca ccacctactt cgtgaccaag
accctgctgc tgaccagcct gttcctgtgg 900atccgcaccg cctacccccg cttccgctac
gaccagctga tgcacctgct gtggaagaac 960ttcctgcccc tgaccctggc cctgctgatg
tggtacgtga gcatgcccat caccatcagc 1020agcatccccc cccagaccta agagcactgg
gacgcccacc gcccctttcc ctccgctgcc 1080aggcgagcat gttgtggtaa ttctggaaca
caagaagaga aattgctggg tttagaacaa 1140gattataaac gaattcggtg ctcagtgatc
acttgacagt tttttttttt tttaaatatt 1200acccaaaatg ctccccaaat aagaaatgca
tcagctcagt cagtgaatac aaaaaaggaa 1260ttatttttcc ctttgagggt cttttataca
tctctcctcc aaccccaccc tctattctgt 1320ttcttcctcc tcacatgggg gtacacatac
acagcttcct cttttggttc catccttacc 1380accacaccac acgcacactc cacatgccca
gcagagtggc acttggtggc cagaaagtgt 1440gagcctcatg atctgctgtc tgtagttctg
tgagctcagg tccctcaaag gcctcggagc 1500acccccttcc ttgtgactga gccagggcct
gcatttttgg ttttccccac cccacacatt 1560ctcaaccata gtccttctaa caataccaat
agctaggacc cggctgctgt gcactgggac 1620tggggattcc acatgtttgc cttgggagtc
tcaagctgga ctgcca 1666572892DNAArtificial
SequenceCOX8-ND4-3'UTR 57atgtccgtcc tgacgcgcct gctgctgcgg ggcttgacac
ggctcggctc ggcggctcca 60gtgcggcgcg ccagaatcca ttcgttgatg ctaaaactaa
tcgtcccaac aattatgtta 120ctaccactga catggctttc caaaaaacac atgatttgga
tcaacacaac cacccacagc 180ctaattatta gcatcatccc tctactattt tttaaccaaa
tcaacaacaa cctatttagc 240tgttccccaa ccttttcctc cgacccccta acaacccccc
tcctaatgct aactacctgg 300ctcctacccc tcacaatcat ggcaagccaa cgccacttat
ccagtgaacc actatcacga 360aaaaaactct acctctctat gctaatctcc ctacaaatct
ccttaattat gacattcaca 420gccacagaac taatcatgtt ttatatcttc ttcgaaacca
cacttatccc caccttggct 480atcatcaccc gatggggcaa ccagccagaa cgcctgaacg
caggcacata cttcctattc 540tacaccctag taggctccct tcccctactc atcgcactaa
tttacactca caacacccta 600ggctcactaa acattctact actcactctc actgcccaag
aactatcaaa ctcctgggcc 660aacaacttaa tgtggctagc ttacacaatg gcttttatgg
taaagatgcc tctttacgga 720ctccacttat ggctccctaa agcccatgtc gaagccccca
tcgctgggtc aatggtactt 780gccgcagtac tcttaaaact aggcggctat ggtatgatgc
gcctcacact cattctcaac 840cccctgacaa aacacatggc ctaccccttc cttgtactat
ccctatgggg catgattatg 900acaagctcca tctgcctacg acaaacagac ctaaaatcgc
tcattgcata ctcttcaatc 960agccacatgg ccctcgtagt aacagccatt ctcatccaaa
ccccctggag cttcaccggc 1020gcagtcattc tcatgatcgc ccacgggctt acatcctcat
tactattctg cctagcaaac 1080tcaaactacg aacgcactca cagtcgcatc atgatcctct
ctcaaggact tcaaactcta 1140ctcccactaa tggctttttg gtggcttcta gcaagcctcg
ctaacctcgc cttacccccc 1200actattaacc tactgggaga actctctgtg ctagtaacca
cgttctcctg gtcaaatatc 1260actctcctac ttacaggact caacatgcta gtcacagccc
tatactccct ctacatgttt 1320accacaacac aatggggctc actcacccac cacattaaca
acatgaaacc ctcattcaca 1380cgagaaaaca ccctcatgtt catgcaccta tcccccattc
tcctcctatc cctcaacccc 1440gacatcatta ccgggttttc ctcttaagag cactgggacg
cccaccgccc ctttccctcc 1500gctgccaggc gagcatgttg tggtaattct ggaacacaag
aagagaaatt gctgggttta 1560gaacaagatt ataaacgaat tcggtgctca gtgatcactt
gacagttttt ttttttttta 1620aatattaccc aaaatgctcc ccaaataaga aatgcatcag
ctcagtcagt gaatacaaaa 1680aaggaattat ttttcccttt gagggtcttt tatacatctc
tcctccaacc ccaccctcta 1740ttctgtttct tcctcctcac atgggggtac acatacacag
cttcctcttt tggttccatc 1800cttaccacca caccacacgc acactccaca tgcccagcag
agtggcactt ggtggccaga 1860aagtgtgagc ctcatgatct gctgtctgta gttctgtgag
ctcaggtccc tcaaaggcct 1920cggagcaccc ccttccttgt gactgagcca gggcctgcat
ttttggtttt ccccacccca 1980cacattctca accatagtcc ttctaacaat accaatagct
aggacccggc tgctgtgcac 2040tgggactggg gattccacat gtttgccttg ggagtctcaa
gctggactgc cagcccctgt 2100cctcccttca cccccattgc gtatgagcat ttcagaactc
caaggagtca caggcatctt 2160tatagttcac gttaacatat agacactgtt ggaagcagtt
ccttctaaaa gggtagccct 2220ggacttaata ccagccggat acctctggcc cccaccccat
tactgtacct ctggagtcac 2280tactgtgggt cgccactcct ctgctacaca gcacggcttt
ttcaaggctg tattgagaag 2340ggaagttagg aagaagggtg tgctgggcta accagcccac
agagctcaca ttcctgtccc 2400ttgggtgaaa aatacatgtc catcctgata tctcctgaat
tcagaaatta gcctccacat 2460gtgcaatggc tttaagagcc agaagcaggg ttctgggaat
tttgcaagtt acctgtggcc 2520aggtgtggtc tcggttacca aatacggtta cctgcagctt
tttagtcctt tgtgctccca 2580cgggtctaca gagtcccatc tgcccaaagg tcttgaagct
tgacaggatg ttttcgatta 2640ctcagtctcc cagggcacta ctggtccgta ggattcgatt
ggtcggggta ggagagttaa 2700acaacattta aacagagttc tctcaaaaat gtctaaaggg
attgtaggta gataacatcc 2760aatcactgtt tgcacttatc tgaaatcttc cctcttggct
gcccccaggt atttactgtg 2820gagaacattg cataggaatg tctggaaaaa gcttctacaa
cttgttacag ccttcacatt 2880tgtagaagct tt
2892582092DNAArtificial SequenceCOX8-ND4-3'UTR*
58atgtccgtcc tgacgcgcct gctgctgcgg ggcttgacac ggctcggctc ggcggctcca
60gtgcggcgcg ccagaatcca ttcgttgatg ctaaaactaa tcgtcccaac aattatgtta
120ctaccactga catggctttc caaaaaacac atgatttgga tcaacacaac cacccacagc
180ctaattatta gcatcatccc tctactattt tttaaccaaa tcaacaacaa cctatttagc
240tgttccccaa ccttttcctc cgacccccta acaacccccc tcctaatgct aactacctgg
300ctcctacccc tcacaatcat ggcaagccaa cgccacttat ccagtgaacc actatcacga
360aaaaaactct acctctctat gctaatctcc ctacaaatct ccttaattat gacattcaca
420gccacagaac taatcatgtt ttatatcttc ttcgaaacca cacttatccc caccttggct
480atcatcaccc gatggggcaa ccagccagaa cgcctgaacg caggcacata cttcctattc
540tacaccctag taggctccct tcccctactc atcgcactaa tttacactca caacacccta
600ggctcactaa acattctact actcactctc actgcccaag aactatcaaa ctcctgggcc
660aacaacttaa tgtggctagc ttacacaatg gcttttatgg taaagatgcc tctttacgga
720ctccacttat ggctccctaa agcccatgtc gaagccccca tcgctgggtc aatggtactt
780gccgcagtac tcttaaaact aggcggctat ggtatgatgc gcctcacact cattctcaac
840cccctgacaa aacacatggc ctaccccttc cttgtactat ccctatgggg catgattatg
900acaagctcca tctgcctacg acaaacagac ctaaaatcgc tcattgcata ctcttcaatc
960agccacatgg ccctcgtagt aacagccatt ctcatccaaa ccccctggag cttcaccggc
1020gcagtcattc tcatgatcgc ccacgggctt acatcctcat tactattctg cctagcaaac
1080tcaaactacg aacgcactca cagtcgcatc atgatcctct ctcaaggact tcaaactcta
1140ctcccactaa tggctttttg gtggcttcta gcaagcctcg ctaacctcgc cttacccccc
1200actattaacc tactgggaga actctctgtg ctagtaacca cgttctcctg gtcaaatatc
1260actctcctac ttacaggact caacatgcta gtcacagccc tatactccct ctacatgttt
1320accacaacac aatggggctc actcacccac cacattaaca acatgaaacc ctcattcaca
1380cgagaaaaca ccctcatgtt catgcaccta tcccccattc tcctcctatc cctcaacccc
1440gacatcatta ccgggttttc ctcttaagag cactgggacg cccaccgccc ctttccctcc
1500gctgccaggc gagcatgttg tggtaattct ggaacacaag aagagaaatt gctgggttta
1560gaacaagatt ataaacgaat tcggtgctca gtgatcactt gacagttttt ttttttttta
1620aatattaccc aaaatgctcc ccaaataaga aatgcatcag ctcagtcagt gaatacaaaa
1680aaggaattat ttttcccttt gagggtcttt tatacatctc tcctccaacc ccaccctcta
1740ttctgtttct tcctcctcac atgggggtac acatacacag cttcctcttt tggttccatc
1800cttaccacca caccacacgc acactccaca tgcccagcag agtggcactt ggtggccaga
1860aagtgtgagc ctcatgatct gctgtctgta gttctgtgag ctcaggtccc tcaaaggcct
1920cggagcaccc ccttccttgt gactgagcca gggcctgcat ttttggtttt ccccacccca
1980cacattctca accatagtcc ttctaacaat accaatagct aggacccggc tgctgtgcac
2040tgggactggg gattccacat gtttgccttg ggagtctcaa gctggactgc ca
2092592892DNAArtificial SequenceCOX8-opt_ND4-3'UTR 59atgtccgtcc
tgacgcgcct gctgctgcgg ggcttgacac ggctcggctc ggcggctcca 60gtgcggcgcg
ccagaatcca ttcgttgatg ctgaagctga tcgtgcccac catcatgctg 120ctgcctctga
cctggctgag caagaaacac atgatctgga tcaacaccac cacgcacagc 180ctgatcatca
gcatcatccc tctgctgttc ttcaaccaga tcaacaacaa cctgttcagc 240tgcagcccca
ccttcagcag cgaccctctg acaacacctc tgctgatgct gaccacctgg 300ctgctgcccc
tcacaatcat ggcctctcag agacacctga gcagcgagcc cctgagccgg 360aagaaactgt
acctgagcat gctgatctcc ctgcagatct ctctgatcat gaccttcacc 420gccaccgagc
tgatcatgtt ctacatcttt ttcgagacaa cgctgatccc cacactggcc 480atcatcacca
gatggggcaa ccagcctgag agactgaacg ccggcaccta ctttctgttc 540tacaccctcg
tgggcagcct gccactgctg attgccctga tctacaccca caacaccctg 600ggctccctga
acatcctgct gctgacactg acagcccaag agctgagcaa cagctgggcc 660aacaatctga
tgtggctggc ctacacaatg gccttcatgg tcaagatgcc cctgtacggc 720ctgcacctgt
ggctgcctaa agctcatgtg gaagccccta tcgccggctc tatggtgctg 780gctgcagtgc
tgctgaaact cggcggctac ggcatgatgc ggctgaccct gattctgaat 840cccctgacca
agcacatggc ctatccattt ctggtgctga gcctgtgggg catgattatg 900accagcagca
tctgcctgcg gcagaccgat ctgaagtccc tgatcgccta cagctccatc 960agccacatgg
ccctggtggt caccgccatc ctgattcaga ccccttggag ctttacaggc 1020gccgtgatcc
tgatgattgc ccacggcctg acaagcagcc tgctgttttg tctggccaac 1080agcaactacg
agcggaccca cagcagaatc atgatcctgt ctcagggcct gcagaccctc 1140ctgcctctta
tggctttttg gtggctgctg gcctctctgg ccaatctggc actgcctcct 1200accatcaatc
tgctgggcga gctgagcgtg ctggtcacca cattcagctg gtccaatatc 1260accctgctgc
tcaccggcct gaacatgctg gttacagccc tgtactccct gtacatgttc 1320accaccacac
agtggggaag cctgacacac cacatcaaca atatgaagcc cagcttcacc 1380cgcgagaaca
ccctgatgtt catgcatctg agccccattc tgctgctgtc cctgaatcct 1440gatatcatca
ccggcttctc cagctgagag cactgggacg cccaccgccc ctttccctcc 1500gctgccaggc
gagcatgttg tggtaattct ggaacacaag aagagaaatt gctgggttta 1560gaacaagatt
ataaacgaat tcggtgctca gtgatcactt gacagttttt ttttttttta 1620aatattaccc
aaaatgctcc ccaaataaga aatgcatcag ctcagtcagt gaatacaaaa 1680aaggaattat
ttttcccttt gagggtcttt tatacatctc tcctccaacc ccaccctcta 1740ttctgtttct
tcctcctcac atgggggtac acatacacag cttcctcttt tggttccatc 1800cttaccacca
caccacacgc acactccaca tgcccagcag agtggcactt ggtggccaga 1860aagtgtgagc
ctcatgatct gctgtctgta gttctgtgag ctcaggtccc tcaaaggcct 1920cggagcaccc
ccttccttgt gactgagcca gggcctgcat ttttggtttt ccccacccca 1980cacattctca
accatagtcc ttctaacaat accaatagct aggacccggc tgctgtgcac 2040tgggactggg
gattccacat gtttgccttg ggagtctcaa gctggactgc cagcccctgt 2100cctcccttca
cccccattgc gtatgagcat ttcagaactc caaggagtca caggcatctt 2160tatagttcac
gttaacatat agacactgtt ggaagcagtt ccttctaaaa gggtagccct 2220ggacttaata
ccagccggat acctctggcc cccaccccat tactgtacct ctggagtcac 2280tactgtgggt
cgccactcct ctgctacaca gcacggcttt ttcaaggctg tattgagaag 2340ggaagttagg
aagaagggtg tgctgggcta accagcccac agagctcaca ttcctgtccc 2400ttgggtgaaa
aatacatgtc catcctgata tctcctgaat tcagaaatta gcctccacat 2460gtgcaatggc
tttaagagcc agaagcaggg ttctgggaat tttgcaagtt acctgtggcc 2520aggtgtggtc
tcggttacca aatacggtta cctgcagctt tttagtcctt tgtgctccca 2580cgggtctaca
gagtcccatc tgcccaaagg tcttgaagct tgacaggatg ttttcgatta 2640ctcagtctcc
cagggcacta ctggtccgta ggattcgatt ggtcggggta ggagagttaa 2700acaacattta
aacagagttc tctcaaaaat gtctaaaggg attgtaggta gataacatcc 2760aatcactgtt
tgcacttatc tgaaatcttc cctcttggct gcccccaggt atttactgtg 2820gagaacattg
cataggaatg tctggaaaaa gcttctacaa cttgttacag ccttcacatt 2880tgtagaagct
tt
2892602092DNAArtificial SequenceCOX8-opt_ND4-3'UTR* 60atgtccgtcc
tgacgcgcct gctgctgcgg ggcttgacac ggctcggctc ggcggctcca 60gtgcggcgcg
ccagaatcca ttcgttgatg ctgaagctga tcgtgcccac catcatgctg 120ctgcctctga
cctggctgag caagaaacac atgatctgga tcaacaccac cacgcacagc 180ctgatcatca
gcatcatccc tctgctgttc ttcaaccaga tcaacaacaa cctgttcagc 240tgcagcccca
ccttcagcag cgaccctctg acaacacctc tgctgatgct gaccacctgg 300ctgctgcccc
tcacaatcat ggcctctcag agacacctga gcagcgagcc cctgagccgg 360aagaaactgt
acctgagcat gctgatctcc ctgcagatct ctctgatcat gaccttcacc 420gccaccgagc
tgatcatgtt ctacatcttt ttcgagacaa cgctgatccc cacactggcc 480atcatcacca
gatggggcaa ccagcctgag agactgaacg ccggcaccta ctttctgttc 540tacaccctcg
tgggcagcct gccactgctg attgccctga tctacaccca caacaccctg 600ggctccctga
acatcctgct gctgacactg acagcccaag agctgagcaa cagctgggcc 660aacaatctga
tgtggctggc ctacacaatg gccttcatgg tcaagatgcc cctgtacggc 720ctgcacctgt
ggctgcctaa agctcatgtg gaagccccta tcgccggctc tatggtgctg 780gctgcagtgc
tgctgaaact cggcggctac ggcatgatgc ggctgaccct gattctgaat 840cccctgacca
agcacatggc ctatccattt ctggtgctga gcctgtgggg catgattatg 900accagcagca
tctgcctgcg gcagaccgat ctgaagtccc tgatcgccta cagctccatc 960agccacatgg
ccctggtggt caccgccatc ctgattcaga ccccttggag ctttacaggc 1020gccgtgatcc
tgatgattgc ccacggcctg acaagcagcc tgctgttttg tctggccaac 1080agcaactacg
agcggaccca cagcagaatc atgatcctgt ctcagggcct gcagaccctc 1140ctgcctctta
tggctttttg gtggctgctg gcctctctgg ccaatctggc actgcctcct 1200accatcaatc
tgctgggcga gctgagcgtg ctggtcacca cattcagctg gtccaatatc 1260accctgctgc
tcaccggcct gaacatgctg gttacagccc tgtactccct gtacatgttc 1320accaccacac
agtggggaag cctgacacac cacatcaaca atatgaagcc cagcttcacc 1380cgcgagaaca
ccctgatgtt catgcatctg agccccattc tgctgctgtc cctgaatcct 1440gatatcatca
ccggcttctc cagctgagag cactgggacg cccaccgccc ctttccctcc 1500gctgccaggc
gagcatgttg tggtaattct ggaacacaag aagagaaatt gctgggttta 1560gaacaagatt
ataaacgaat tcggtgctca gtgatcactt gacagttttt ttttttttta 1620aatattaccc
aaaatgctcc ccaaataaga aatgcatcag ctcagtcagt gaatacaaaa 1680aaggaattat
ttttcccttt gagggtcttt tatacatctc tcctccaacc ccaccctcta 1740ttctgtttct
tcctcctcac atgggggtac acatacacag cttcctcttt tggttccatc 1800cttaccacca
caccacacgc acactccaca tgcccagcag agtggcactt ggtggccaga 1860aagtgtgagc
ctcatgatct gctgtctgta gttctgtgag ctcaggtccc tcaaaggcct 1920cggagcaccc
ccttccttgt gactgagcca gggcctgcat ttttggtttt ccccacccca 1980cacattctca
accatagtcc ttctaacaat accaatagct aggacccggc tgctgtgcac 2040tgggactggg
gattccacat gtttgccttg ggagtctcaa gctggactgc ca
2092612892DNAArtificial SequenceCOX8-opt_ND4*-3'UTR 61atgtccgtcc
tgacgcgcct gctgctgcgg ggcttgacac ggctcggctc ggcggctcca 60gtgcggcgcg
ccagaatcca ttcgttgatg ctgaagctga tcgtgcccac catcatgctg 120ctgcccctga
cctggctgag caagaagcac atgatctgga tcaacaccac cacccacagc 180ctgatcatca
gcatcatccc cctgctgttc ttcaaccaga tcaacaacaa cctgttcagc 240tgcagcccca
ccttcagcag cgaccccctg accacccccc tgctgatgct gaccacctgg 300ctgctgcccc
tgaccatcat ggccagccag cgccacctga gcagcgagcc cctgagccgc 360aagaagctgt
acctgagcat gctgatcagc ctgcagatca gcctgatcat gaccttcacc 420gccaccgagc
tgatcatgtt ctacatcttc ttcgagacca ccctgatccc caccctggcc 480atcatcaccc
gctggggcaa ccagcccgag cgcctgaacg ccggcaccta cttcctgttc 540tacaccctgg
tgggcagcct gcccctgctg atcgccctga tctacaccca caacaccctg 600ggcagcctga
acatcctgct gctgaccctg accgcccagg agctgagcaa cagctgggcc 660aacaacctga
tgtggctggc ctacaccatg gccttcatgg tgaagatgcc cctgtacggc 720ctgcacctgt
ggctgcccaa ggcccacgtg gaggccccca tcgccggcag catggtgctg 780gccgccgtgc
tgctgaagct gggcggctac ggcatgatgc gcctgaccct gatcctgaac 840cccctgacca
agcacatggc ctaccccttc ctggtgctga gcctgtgggg catgatcatg 900accagcagca
tctgcctgcg ccagaccgac ctgaagagcc tgatcgccta cagcagcatc 960agccacatgg
ccctggtggt gaccgccatc ctgatccaga ccccctggag cttcaccggc 1020gccgtgatcc
tgatgatcgc ccacggcctg accagcagcc tgctgttctg cctggccaac 1080agcaactacg
agcgcaccca cagccgcatc atgatcctga gccagggcct gcagaccctg 1140ctgcccctga
tggccttctg gtggctgctg gccagcctgg ccaacctggc cctgcccccc 1200accatcaacc
tgctgggcga gctgagcgtg ctggtgacca ccttcagctg gagcaacatc 1260accctgctgc
tgaccggcct gaacatgctg gtgaccgccc tgtacagcct gtacatgttc 1320accaccaccc
agtggggcag cctgacccac cacatcaaca acatgaagcc cagcttcacc 1380cgcgagaaca
ccctgatgtt catgcacctg agccccatcc tgctgctgag cctgaacccc 1440gacatcatca
ccggcttcag cagctaagag cactgggacg cccaccgccc ctttccctcc 1500gctgccaggc
gagcatgttg tggtaattct ggaacacaag aagagaaatt gctgggttta 1560gaacaagatt
ataaacgaat tcggtgctca gtgatcactt gacagttttt ttttttttta 1620aatattaccc
aaaatgctcc ccaaataaga aatgcatcag ctcagtcagt gaatacaaaa 1680aaggaattat
ttttcccttt gagggtcttt tatacatctc tcctccaacc ccaccctcta 1740ttctgtttct
tcctcctcac atgggggtac acatacacag cttcctcttt tggttccatc 1800cttaccacca
caccacacgc acactccaca tgcccagcag agtggcactt ggtggccaga 1860aagtgtgagc
ctcatgatct gctgtctgta gttctgtgag ctcaggtccc tcaaaggcct 1920cggagcaccc
ccttccttgt gactgagcca gggcctgcat ttttggtttt ccccacccca 1980cacattctca
accatagtcc ttctaacaat accaatagct aggacccggc tgctgtgcac 2040tgggactggg
gattccacat gtttgccttg ggagtctcaa gctggactgc cagcccctgt 2100cctcccttca
cccccattgc gtatgagcat ttcagaactc caaggagtca caggcatctt 2160tatagttcac
gttaacatat agacactgtt ggaagcagtt ccttctaaaa gggtagccct 2220ggacttaata
ccagccggat acctctggcc cccaccccat tactgtacct ctggagtcac 2280tactgtgggt
cgccactcct ctgctacaca gcacggcttt ttcaaggctg tattgagaag 2340ggaagttagg
aagaagggtg tgctgggcta accagcccac agagctcaca ttcctgtccc 2400ttgggtgaaa
aatacatgtc catcctgata tctcctgaat tcagaaatta gcctccacat 2460gtgcaatggc
tttaagagcc agaagcaggg ttctgggaat tttgcaagtt acctgtggcc 2520aggtgtggtc
tcggttacca aatacggtta cctgcagctt tttagtcctt tgtgctccca 2580cgggtctaca
gagtcccatc tgcccaaagg tcttgaagct tgacaggatg ttttcgatta 2640ctcagtctcc
cagggcacta ctggtccgta ggattcgatt ggtcggggta ggagagttaa 2700acaacattta
aacagagttc tctcaaaaat gtctaaaggg attgtaggta gataacatcc 2760aatcactgtt
tgcacttatc tgaaatcttc cctcttggct gcccccaggt atttactgtg 2820gagaacattg
cataggaatg tctggaaaaa gcttctacaa cttgttacag ccttcacatt 2880tgtagaagct
tt
2892622092DNAArtificial SequenceCOX8-opt_ND4*-3'UTR* 62atgtccgtcc
tgacgcgcct gctgctgcgg ggcttgacac ggctcggctc ggcggctcca 60gtgcggcgcg
ccagaatcca ttcgttgatg ctgaagctga tcgtgcccac catcatgctg 120ctgcccctga
cctggctgag caagaagcac atgatctgga tcaacaccac cacccacagc 180ctgatcatca
gcatcatccc cctgctgttc ttcaaccaga tcaacaacaa cctgttcagc 240tgcagcccca
ccttcagcag cgaccccctg accacccccc tgctgatgct gaccacctgg 300ctgctgcccc
tgaccatcat ggccagccag cgccacctga gcagcgagcc cctgagccgc 360aagaagctgt
acctgagcat gctgatcagc ctgcagatca gcctgatcat gaccttcacc 420gccaccgagc
tgatcatgtt ctacatcttc ttcgagacca ccctgatccc caccctggcc 480atcatcaccc
gctggggcaa ccagcccgag cgcctgaacg ccggcaccta cttcctgttc 540tacaccctgg
tgggcagcct gcccctgctg atcgccctga tctacaccca caacaccctg 600ggcagcctga
acatcctgct gctgaccctg accgcccagg agctgagcaa cagctgggcc 660aacaacctga
tgtggctggc ctacaccatg gccttcatgg tgaagatgcc cctgtacggc 720ctgcacctgt
ggctgcccaa ggcccacgtg gaggccccca tcgccggcag catggtgctg 780gccgccgtgc
tgctgaagct gggcggctac ggcatgatgc gcctgaccct gatcctgaac 840cccctgacca
agcacatggc ctaccccttc ctggtgctga gcctgtgggg catgatcatg 900accagcagca
tctgcctgcg ccagaccgac ctgaagagcc tgatcgccta cagcagcatc 960agccacatgg
ccctggtggt gaccgccatc ctgatccaga ccccctggag cttcaccggc 1020gccgtgatcc
tgatgatcgc ccacggcctg accagcagcc tgctgttctg cctggccaac 1080agcaactacg
agcgcaccca cagccgcatc atgatcctga gccagggcct gcagaccctg 1140ctgcccctga
tggccttctg gtggctgctg gccagcctgg ccaacctggc cctgcccccc 1200accatcaacc
tgctgggcga gctgagcgtg ctggtgacca ccttcagctg gagcaacatc 1260accctgctgc
tgaccggcct gaacatgctg gtgaccgccc tgtacagcct gtacatgttc 1320accaccaccc
agtggggcag cctgacccac cacatcaaca acatgaagcc cagcttcacc 1380cgcgagaaca
ccctgatgtt catgcacctg agccccatcc tgctgctgag cctgaacccc 1440gacatcatca
ccggcttcag cagctaagag cactgggacg cccaccgccc ctttccctcc 1500gctgccaggc
gagcatgttg tggtaattct ggaacacaag aagagaaatt gctgggttta 1560gaacaagatt
ataaacgaat tcggtgctca gtgatcactt gacagttttt ttttttttta 1620aatattaccc
aaaatgctcc ccaaataaga aatgcatcag ctcagtcagt gaatacaaaa 1680aaggaattat
ttttcccttt gagggtcttt tatacatctc tcctccaacc ccaccctcta 1740ttctgtttct
tcctcctcac atgggggtac acatacacag cttcctcttt tggttccatc 1800cttaccacca
caccacacgc acactccaca tgcccagcag agtggcactt ggtggccaga 1860aagtgtgagc
ctcatgatct gctgtctgta gttctgtgag ctcaggtccc tcaaaggcct 1920cggagcaccc
ccttccttgt gactgagcca gggcctgcat ttttggtttt ccccacccca 1980cacattctca
accatagtcc ttctaacaat accaatagct aggacccggc tgctgtgcac 2040tgggactggg
gattccacat gtttgccttg ggagtctcaa gctggactgc ca
2092632037DNAArtificial SequenceCOX8-ND6-3'UTR 63atgtccgtcc tgacgcgcct
gctgctgcgg ggcttgacac ggctcggctc ggcggctcca 60gtgcggcgcg ccagaatcca
ttcgttgatg atgtatgctt tgtttctgtt gagtgtgggt 120ttagtaatgg ggtttgtggg
gttttcttct aagccttctc ctatttatgg gggtttagta 180ttgattgtta gcggtgtggt
cgggtgtgtt attattctga attttggggg aggttatatg 240ggtttaatgg tttttttaat
ttatttaggg ggaatgatgg ttgtctttgg atatactaca 300gcgatggcta ttgaggagta
tcctgaggca tgggggtcag gggttgaggt cttggtgagt 360gttttagtgg ggttagcgat
ggaggtagga ttggtgctgt gggtgaaaga gtatgatggg 420gtggtggttg tggtaaactt
taatagtgta ggaagctgga tgatttatga aggagagggg 480tcagggttga ttcgggagga
tcctattggt gcgggggctt tgtatgatta tgggcgttgg 540ttagtagtag ttactggttg
gacattgttt gttggtgtat atattgtaat tgagattgct 600cgggggaatt aggagcactg
ggacgcccac cgcccctttc cctccgctgc caggcgagca 660tgttgtggta attctggaac
acaagaagag aaattgctgg gtttagaaca agattataaa 720cgaattcggt gctcagtgat
cacttgacag tttttttttt ttttaaatat tacccaaaat 780gctccccaaa taagaaatgc
atcagctcag tcagtgaata caaaaaagga attatttttc 840cctttgaggg tcttttatac
atctctcctc caaccccacc ctctattctg tttcttcctc 900ctcacatggg ggtacacata
cacagcttcc tcttttggtt ccatccttac caccacacca 960cacgcacact ccacatgccc
agcagagtgg cacttggtgg ccagaaagtg tgagcctcat 1020gatctgctgt ctgtagttct
gtgagctcag gtccctcaaa ggcctcggag cacccccttc 1080cttgtgactg agccagggcc
tgcatttttg gttttcccca ccccacacat tctcaaccat 1140agtccttcta acaataccaa
tagctaggac ccggctgctg tgcactggga ctggggattc 1200cacatgtttg ccttgggagt
ctcaagctgg actgccagcc cctgtcctcc cttcaccccc 1260attgcgtatg agcatttcag
aactccaagg agtcacaggc atctttatag ttcacgttaa 1320catatagaca ctgttggaag
cagttccttc taaaagggta gccctggact taataccagc 1380cggatacctc tggcccccac
cccattactg tacctctgga gtcactactg tgggtcgcca 1440ctcctctgct acacagcacg
gctttttcaa ggctgtattg agaagggaag ttaggaagaa 1500gggtgtgctg ggctaaccag
cccacagagc tcacattcct gtcccttggg tgaaaaatac 1560atgtccatcc tgatatctcc
tgaattcaga aattagcctc cacatgtgca atggctttaa 1620gagccagaag cagggttctg
ggaattttgc aagttacctg tggccaggtg tggtctcggt 1680taccaaatac ggttacctgc
agctttttag tcctttgtgc tcccacgggt ctacagagtc 1740ccatctgccc aaaggtcttg
aagcttgaca ggatgttttc gattactcag tctcccaggg 1800cactactggt ccgtaggatt
cgattggtcg gggtaggaga gttaaacaac atttaaacag 1860agttctctca aaaatgtcta
aagggattgt aggtagataa catccaatca ctgtttgcac 1920ttatctgaaa tcttccctct
tggctgcccc caggtattta ctgtggagaa cattgcatag 1980gaatgtctgg aaaaagcttc
tacaacttgt tacagccttc acatttgtag aagcttt 2037641237DNAArtificial
SequenceCOX8-ND6-3'UTR* 64atgtccgtcc tgacgcgcct gctgctgcgg ggcttgacac
ggctcggctc ggcggctcca 60gtgcggcgcg ccagaatcca ttcgttgatg atgtatgctt
tgtttctgtt gagtgtgggt 120ttagtaatgg ggtttgtggg gttttcttct aagccttctc
ctatttatgg gggtttagta 180ttgattgtta gcggtgtggt cgggtgtgtt attattctga
attttggggg aggttatatg 240ggtttaatgg tttttttaat ttatttaggg ggaatgatgg
ttgtctttgg atatactaca 300gcgatggcta ttgaggagta tcctgaggca tgggggtcag
gggttgaggt cttggtgagt 360gttttagtgg ggttagcgat ggaggtagga ttggtgctgt
gggtgaaaga gtatgatggg 420gtggtggttg tggtaaactt taatagtgta ggaagctgga
tgatttatga aggagagggg 480tcagggttga ttcgggagga tcctattggt gcgggggctt
tgtatgatta tgggcgttgg 540ttagtagtag ttactggttg gacattgttt gttggtgtat
atattgtaat tgagattgct 600cgggggaatt aggagcactg ggacgcccac cgcccctttc
cctccgctgc caggcgagca 660tgttgtggta attctggaac acaagaagag aaattgctgg
gtttagaaca agattataaa 720cgaattcggt gctcagtgat cacttgacag tttttttttt
ttttaaatat tacccaaaat 780gctccccaaa taagaaatgc atcagctcag tcagtgaata
caaaaaagga attatttttc 840cctttgaggg tcttttatac atctctcctc caaccccacc
ctctattctg tttcttcctc 900ctcacatggg ggtacacata cacagcttcc tcttttggtt
ccatccttac caccacacca 960cacgcacact ccacatgccc agcagagtgg cacttggtgg
ccagaaagtg tgagcctcat 1020gatctgctgt ctgtagttct gtgagctcag gtccctcaaa
ggcctcggag cacccccttc 1080cttgtgactg agccagggcc tgcatttttg gttttcccca
ccccacacat tctcaaccat 1140agtccttcta acaataccaa tagctaggac ccggctgctg
tgcactggga ctggggattc 1200cacatgtttg ccttgggagt ctcaagctgg actgcca
1237652037DNAArtificial SequenceCOX8-opt_ND6-3'UTR
65atgtccgtcc tgacgcgcct gctgctgcgg ggcttgacac ggctcggctc ggcggctcca
60gtgcggcgcg ccagaatcca ttcgttgatg atgtacgccc tgttcctgct gagcgtgggc
120ctggtgatgg gcttcgtggg cttcagcagc aagcccagcc ccatctacgg cggcctggtg
180ctgatcgtga gcggcgtggt gggctgcgtg atcatcctga acttcggcgg cggctacatg
240ggcctgatgg tgttcctgat ctacctgggc ggcatgatgg tggtgttcgg ctacaccacc
300gccatggcca tcgaggagta ccccgaggcc tggggcagcg gcgtggaggt gctggtgagc
360gtgctggtgg gcctggccat ggaggtgggc ctggtgctgt gggtgaagga gtacgacggc
420gtggtggtgg tggtgaactt caacagcgtg ggcagctgga tgatctacga gggcgagggc
480agcggcctga tccgcgagga ccccatcggc gccggcgccc tgtacgacta cggccgctgg
540ctggtggtgg tgaccggctg gaccctgttc gtgggcgtgt acatcgtgat cgagatcgcc
600cgcggcaact aagagcactg ggacgcccac cgcccctttc cctccgctgc caggcgagca
660tgttgtggta attctggaac acaagaagag aaattgctgg gtttagaaca agattataaa
720cgaattcggt gctcagtgat cacttgacag tttttttttt ttttaaatat tacccaaaat
780gctccccaaa taagaaatgc atcagctcag tcagtgaata caaaaaagga attatttttc
840cctttgaggg tcttttatac atctctcctc caaccccacc ctctattctg tttcttcctc
900ctcacatggg ggtacacata cacagcttcc tcttttggtt ccatccttac caccacacca
960cacgcacact ccacatgccc agcagagtgg cacttggtgg ccagaaagtg tgagcctcat
1020gatctgctgt ctgtagttct gtgagctcag gtccctcaaa ggcctcggag cacccccttc
1080cttgtgactg agccagggcc tgcatttttg gttttcccca ccccacacat tctcaaccat
1140agtccttcta acaataccaa tagctaggac ccggctgctg tgcactggga ctggggattc
1200cacatgtttg ccttgggagt ctcaagctgg actgccagcc cctgtcctcc cttcaccccc
1260attgcgtatg agcatttcag aactccaagg agtcacaggc atctttatag ttcacgttaa
1320catatagaca ctgttggaag cagttccttc taaaagggta gccctggact taataccagc
1380cggatacctc tggcccccac cccattactg tacctctgga gtcactactg tgggtcgcca
1440ctcctctgct acacagcacg gctttttcaa ggctgtattg agaagggaag ttaggaagaa
1500gggtgtgctg ggctaaccag cccacagagc tcacattcct gtcccttggg tgaaaaatac
1560atgtccatcc tgatatctcc tgaattcaga aattagcctc cacatgtgca atggctttaa
1620gagccagaag cagggttctg ggaattttgc aagttacctg tggccaggtg tggtctcggt
1680taccaaatac ggttacctgc agctttttag tcctttgtgc tcccacgggt ctacagagtc
1740ccatctgccc aaaggtcttg aagcttgaca ggatgttttc gattactcag tctcccaggg
1800cactactggt ccgtaggatt cgattggtcg gggtaggaga gttaaacaac atttaaacag
1860agttctctca aaaatgtcta aagggattgt aggtagataa catccaatca ctgtttgcac
1920ttatctgaaa tcttccctct tggctgcccc caggtattta ctgtggagaa cattgcatag
1980gaatgtctgg aaaaagcttc tacaacttgt tacagccttc acatttgtag aagcttt
2037661237DNAArtificial SequenceCOX8-opt_ND6-3'UTR* 66atgtccgtcc
tgacgcgcct gctgctgcgg ggcttgacac ggctcggctc ggcggctcca 60gtgcggcgcg
ccagaatcca ttcgttgatg atgtacgccc tgttcctgct gagcgtgggc 120ctggtgatgg
gcttcgtggg cttcagcagc aagcccagcc ccatctacgg cggcctggtg 180ctgatcgtga
gcggcgtggt gggctgcgtg atcatcctga acttcggcgg cggctacatg 240ggcctgatgg
tgttcctgat ctacctgggc ggcatgatgg tggtgttcgg ctacaccacc 300gccatggcca
tcgaggagta ccccgaggcc tggggcagcg gcgtggaggt gctggtgagc 360gtgctggtgg
gcctggccat ggaggtgggc ctggtgctgt gggtgaagga gtacgacggc 420gtggtggtgg
tggtgaactt caacagcgtg ggcagctgga tgatctacga gggcgagggc 480agcggcctga
tccgcgagga ccccatcggc gccggcgccc tgtacgacta cggccgctgg 540ctggtggtgg
tgaccggctg gaccctgttc gtgggcgtgt acatcgtgat cgagatcgcc 600cgcggcaact
aagagcactg ggacgcccac cgcccctttc cctccgctgc caggcgagca 660tgttgtggta
attctggaac acaagaagag aaattgctgg gtttagaaca agattataaa 720cgaattcggt
gctcagtgat cacttgacag tttttttttt ttttaaatat tacccaaaat 780gctccccaaa
taagaaatgc atcagctcag tcagtgaata caaaaaagga attatttttc 840cctttgaggg
tcttttatac atctctcctc caaccccacc ctctattctg tttcttcctc 900ctcacatggg
ggtacacata cacagcttcc tcttttggtt ccatccttac caccacacca 960cacgcacact
ccacatgccc agcagagtgg cacttggtgg ccagaaagtg tgagcctcat 1020gatctgctgt
ctgtagttct gtgagctcag gtccctcaaa ggcctcggag cacccccttc 1080cttgtgactg
agccagggcc tgcatttttg gttttcccca ccccacacat tctcaaccat 1140agtccttcta
acaataccaa tagctaggac ccggctgctg tgcactggga ctggggattc 1200cacatgtttg
ccttgggagt ctcaagctgg actgcca
1237672469DNAArtificial SequenceCOX8-ND1-3'UTR 67atgtccgtcc tgacgcgcct
gctgctgcgg ggcttgacac ggctcggctc ggcggctcca 60gtgcggcgcg ccagaatcca
ttcgttgatg cccatggcca acctcctact cctcattgta 120cccattctaa tcgcaatggc
attcctaatg cttaccgaac gaaaaattct aggctatatg 180caactacgca aaggccccaa
cgttgtaggc ccctacgggc tactacaacc cttcgctgac 240gccatgaaac tcttcaccaa
agagccccta aaacccgcca catctaccat caccctctac 300atcaccgccc cgaccttagc
tctcaccatc gctcttctac tatggacccc cctccccatg 360cccaaccccc tggtcaacct
caacctaggc ctcctattta ttctagccac ctctagccta 420gccgtttact caatcctctg
gtcagggtgg gcatcaaact caaactacgc cctgatcggc 480gcactgcgag cagtagccca
aacaatctca tatgaagtca ccctagccat cattctacta 540tcaacattac taatgagtgg
ctcctttaac ctctccaccc ttatcacaac acaagaacac 600ctctggttac tcctgccatc
atggcccttg gccatgatgt ggtttatctc cacactagca 660gagaccaacc gaaccccctt
cgaccttgcc gaaggggagt ccgaactagt ctcaggcttc 720aacatcgaat acgccgcagg
ccccttcgcc ctattcttca tggccgaata cacaaacatt 780attatgatga acaccctcac
cactacaatc ttcctaggaa caacatatga cgcactctcc 840cctgaactct acacaacata
ttttgtcacc aagaccctac ttctaacctc cctgttctta 900tggattcgaa cagcataccc
ccgattccgc tacgaccaac tcatgcacct cctatggaaa 960aacttcctac cactcaccct
agcattactt atgtggtatg tctccatgcc cattacaatc 1020tccagcattc cccctcaaac
ctaagagcac tgggacgccc accgcccctt tccctccgct 1080gccaggcgag catgttgtgg
taattctgga acacaagaag agaaattgct gggtttagaa 1140caagattata aacgaattcg
gtgctcagtg atcacttgac agtttttttt ttttttaaat 1200attacccaaa atgctcccca
aataagaaat gcatcagctc agtcagtgaa tacaaaaaag 1260gaattatttt tccctttgag
ggtcttttat acatctctcc tccaacccca ccctctattc 1320tgtttcttcc tcctcacatg
ggggtacaca tacacagctt cctcttttgg ttccatcctt 1380accaccacac cacacgcaca
ctccacatgc ccagcagagt ggcacttggt ggccagaaag 1440tgtgagcctc atgatctgct
gtctgtagtt ctgtgagctc aggtccctca aaggcctcgg 1500agcaccccct tccttgtgac
tgagccaggg cctgcatttt tggttttccc caccccacac 1560attctcaacc atagtccttc
taacaatacc aatagctagg acccggctgc tgtgcactgg 1620gactggggat tccacatgtt
tgccttggga gtctcaagct ggactgccag cccctgtcct 1680cccttcaccc ccattgcgta
tgagcatttc agaactccaa ggagtcacag gcatctttat 1740agttcacgtt aacatataga
cactgttgga agcagttcct tctaaaaggg tagccctgga 1800cttaatacca gccggatacc
tctggccccc accccattac tgtacctctg gagtcactac 1860tgtgggtcgc cactcctctg
ctacacagca cggctttttc aaggctgtat tgagaaggga 1920agttaggaag aagggtgtgc
tgggctaacc agcccacaga gctcacattc ctgtcccttg 1980ggtgaaaaat acatgtccat
cctgatatct cctgaattca gaaattagcc tccacatgtg 2040caatggcttt aagagccaga
agcagggttc tgggaatttt gcaagttacc tgtggccagg 2100tgtggtctcg gttaccaaat
acggttacct gcagcttttt agtcctttgt gctcccacgg 2160gtctacagag tcccatctgc
ccaaaggtct tgaagcttga caggatgttt tcgattactc 2220agtctcccag ggcactactg
gtccgtagga ttcgattggt cggggtagga gagttaaaca 2280acatttaaac agagttctct
caaaaatgtc taaagggatt gtaggtagat aacatccaat 2340cactgtttgc acttatctga
aatcttccct cttggctgcc cccaggtatt tactgtggag 2400aacattgcat aggaatgtct
ggaaaaagct tctacaactt gttacagcct tcacatttgt 2460agaagcttt
2469681669DNAArtificial
SequenceCOX8-ND1-3'UTR* 68atgtccgtcc tgacgcgcct gctgctgcgg ggcttgacac
ggctcggctc ggcggctcca 60gtgcggcgcg ccagaatcca ttcgttgatg cccatggcca
acctcctact cctcattgta 120cccattctaa tcgcaatggc attcctaatg cttaccgaac
gaaaaattct aggctatatg 180caactacgca aaggccccaa cgttgtaggc ccctacgggc
tactacaacc cttcgctgac 240gccatgaaac tcttcaccaa agagccccta aaacccgcca
catctaccat caccctctac 300atcaccgccc cgaccttagc tctcaccatc gctcttctac
tatggacccc cctccccatg 360cccaaccccc tggtcaacct caacctaggc ctcctattta
ttctagccac ctctagccta 420gccgtttact caatcctctg gtcagggtgg gcatcaaact
caaactacgc cctgatcggc 480gcactgcgag cagtagccca aacaatctca tatgaagtca
ccctagccat cattctacta 540tcaacattac taatgagtgg ctcctttaac ctctccaccc
ttatcacaac acaagaacac 600ctctggttac tcctgccatc atggcccttg gccatgatgt
ggtttatctc cacactagca 660gagaccaacc gaaccccctt cgaccttgcc gaaggggagt
ccgaactagt ctcaggcttc 720aacatcgaat acgccgcagg ccccttcgcc ctattcttca
tggccgaata cacaaacatt 780attatgatga acaccctcac cactacaatc ttcctaggaa
caacatatga cgcactctcc 840cctgaactct acacaacata ttttgtcacc aagaccctac
ttctaacctc cctgttctta 900tggattcgaa cagcataccc ccgattccgc tacgaccaac
tcatgcacct cctatggaaa 960aacttcctac cactcaccct agcattactt atgtggtatg
tctccatgcc cattacaatc 1020tccagcattc cccctcaaac ctaagagcac tgggacgccc
accgcccctt tccctccgct 1080gccaggcgag catgttgtgg taattctgga acacaagaag
agaaattgct gggtttagaa 1140caagattata aacgaattcg gtgctcagtg atcacttgac
agtttttttt ttttttaaat 1200attacccaaa atgctcccca aataagaaat gcatcagctc
agtcagtgaa tacaaaaaag 1260gaattatttt tccctttgag ggtcttttat acatctctcc
tccaacccca ccctctattc 1320tgtttcttcc tcctcacatg ggggtacaca tacacagctt
cctcttttgg ttccatcctt 1380accaccacac cacacgcaca ctccacatgc ccagcagagt
ggcacttggt ggccagaaag 1440tgtgagcctc atgatctgct gtctgtagtt ctgtgagctc
aggtccctca aaggcctcgg 1500agcaccccct tccttgtgac tgagccaggg cctgcatttt
tggttttccc caccccacac 1560attctcaacc atagtccttc taacaatacc aatagctagg
acccggctgc tgtgcactgg 1620gactggggat tccacatgtt tgccttggga gtctcaagct
ggactgcca 1669692469DNAArtificial
SequenceCOX8-opt_ND1-3'UTR 69atgtccgtcc tgacgcgcct gctgctgcgg ggcttgacac
ggctcggctc ggcggctcca 60gtgcggcgcg ccagaatcca ttcgttgatg cccatggcca
acctgctgct gctgatcgtg 120cccatcctga tcgccatggc cttcctgatg ctgaccgagc
gcaagatcct gggctacatg 180cagctgcgca agggccccaa cgtggtgggc ccctacggcc
tgctgcagcc cttcgccgac 240gccatgaagc tgttcaccaa ggagcccctg aagcccgcca
ccagcaccat caccctgtac 300atcaccgccc ccaccctggc cctgaccatc gccctgctgc
tgtggacccc cctgcccatg 360cccaaccccc tggtgaacct gaacctgggc ctgctgttca
tcctggccac cagcagcctg 420gccgtgtaca gcatcctgtg gagcggctgg gccagcaaca
gcaactacgc cctgatcggc 480gccctgcgcg ccgtggccca gaccatcagc tacgaggtga
ccctggccat catcctgctg 540agcaccctgc tgatgagcgg cagcttcaac ctgagcaccc
tgatcaccac ccaggagcac 600ctgtggctgc tgctgcccag ctggcccctg gccatgatgt
ggttcatcag caccctggcc 660gagaccaacc gcaccccctt cgacctggcc gagggcgaga
gcgagctggt gagcggcttc 720aacatcgagt acgccgccgg ccccttcgcc ctgttcttca
tggccgagta caccaacatc 780atcatgatga acaccctgac caccaccatc ttcctgggca
ccacctacga cgccctgagc 840cccgagctgt acaccaccta cttcgtgacc aagaccctgc
tgctgaccag cctgttcctg 900tggatccgca ccgcctaccc ccgcttccgc tacgaccagc
tgatgcacct gctgtggaag 960aacttcctgc ccctgaccct ggccctgctg atgtggtacg
tgagcatgcc catcaccatc 1020agcagcatcc ccccccagac ctaagagcac tgggacgccc
accgcccctt tccctccgct 1080gccaggcgag catgttgtgg taattctgga acacaagaag
agaaattgct gggtttagaa 1140caagattata aacgaattcg gtgctcagtg atcacttgac
agtttttttt ttttttaaat 1200attacccaaa atgctcccca aataagaaat gcatcagctc
agtcagtgaa tacaaaaaag 1260gaattatttt tccctttgag ggtcttttat acatctctcc
tccaacccca ccctctattc 1320tgtttcttcc tcctcacatg ggggtacaca tacacagctt
cctcttttgg ttccatcctt 1380accaccacac cacacgcaca ctccacatgc ccagcagagt
ggcacttggt ggccagaaag 1440tgtgagcctc atgatctgct gtctgtagtt ctgtgagctc
aggtccctca aaggcctcgg 1500agcaccccct tccttgtgac tgagccaggg cctgcatttt
tggttttccc caccccacac 1560attctcaacc atagtccttc taacaatacc aatagctagg
acccggctgc tgtgcactgg 1620gactggggat tccacatgtt tgccttggga gtctcaagct
ggactgccag cccctgtcct 1680cccttcaccc ccattgcgta tgagcatttc agaactccaa
ggagtcacag gcatctttat 1740agttcacgtt aacatataga cactgttgga agcagttcct
tctaaaaggg tagccctgga 1800cttaatacca gccggatacc tctggccccc accccattac
tgtacctctg gagtcactac 1860tgtgggtcgc cactcctctg ctacacagca cggctttttc
aaggctgtat tgagaaggga 1920agttaggaag aagggtgtgc tgggctaacc agcccacaga
gctcacattc ctgtcccttg 1980ggtgaaaaat acatgtccat cctgatatct cctgaattca
gaaattagcc tccacatgtg 2040caatggcttt aagagccaga agcagggttc tgggaatttt
gcaagttacc tgtggccagg 2100tgtggtctcg gttaccaaat acggttacct gcagcttttt
agtcctttgt gctcccacgg 2160gtctacagag tcccatctgc ccaaaggtct tgaagcttga
caggatgttt tcgattactc 2220agtctcccag ggcactactg gtccgtagga ttcgattggt
cggggtagga gagttaaaca 2280acatttaaac agagttctct caaaaatgtc taaagggatt
gtaggtagat aacatccaat 2340cactgtttgc acttatctga aatcttccct cttggctgcc
cccaggtatt tactgtggag 2400aacattgcat aggaatgtct ggaaaaagct tctacaactt
gttacagcct tcacatttgt 2460agaagcttt
2469701669DNAArtificial SequenceCOX8-opt_ND1-3'UTR*
70atgtccgtcc tgacgcgcct gctgctgcgg ggcttgacac ggctcggctc ggcggctcca
60gtgcggcgcg ccagaatcca ttcgttgatg cccatggcca acctgctgct gctgatcgtg
120cccatcctga tcgccatggc cttcctgatg ctgaccgagc gcaagatcct gggctacatg
180cagctgcgca agggccccaa cgtggtgggc ccctacggcc tgctgcagcc cttcgccgac
240gccatgaagc tgttcaccaa ggagcccctg aagcccgcca ccagcaccat caccctgtac
300atcaccgccc ccaccctggc cctgaccatc gccctgctgc tgtggacccc cctgcccatg
360cccaaccccc tggtgaacct gaacctgggc ctgctgttca tcctggccac cagcagcctg
420gccgtgtaca gcatcctgtg gagcggctgg gccagcaaca gcaactacgc cctgatcggc
480gccctgcgcg ccgtggccca gaccatcagc tacgaggtga ccctggccat catcctgctg
540agcaccctgc tgatgagcgg cagcttcaac ctgagcaccc tgatcaccac ccaggagcac
600ctgtggctgc tgctgcccag ctggcccctg gccatgatgt ggttcatcag caccctggcc
660gagaccaacc gcaccccctt cgacctggcc gagggcgaga gcgagctggt gagcggcttc
720aacatcgagt acgccgccgg ccccttcgcc ctgttcttca tggccgagta caccaacatc
780atcatgatga acaccctgac caccaccatc ttcctgggca ccacctacga cgccctgagc
840cccgagctgt acaccaccta cttcgtgacc aagaccctgc tgctgaccag cctgttcctg
900tggatccgca ccgcctaccc ccgcttccgc tacgaccagc tgatgcacct gctgtggaag
960aacttcctgc ccctgaccct ggccctgctg atgtggtacg tgagcatgcc catcaccatc
1020agcagcatcc ccccccagac ctaagagcac tgggacgccc accgcccctt tccctccgct
1080gccaggcgag catgttgtgg taattctgga acacaagaag agaaattgct gggtttagaa
1140caagattata aacgaattcg gtgctcagtg atcacttgac agtttttttt ttttttaaat
1200attacccaaa atgctcccca aataagaaat gcatcagctc agtcagtgaa tacaaaaaag
1260gaattatttt tccctttgag ggtcttttat acatctctcc tccaacccca ccctctattc
1320tgtttcttcc tcctcacatg ggggtacaca tacacagctt cctcttttgg ttccatcctt
1380accaccacac cacacgcaca ctccacatgc ccagcagagt ggcacttggt ggccagaaag
1440tgtgagcctc atgatctgct gtctgtagtt ctgtgagctc aggtccctca aaggcctcgg
1500agcaccccct tccttgtgac tgagccaggg cctgcatttt tggttttccc caccccacac
1560attctcaacc atagtccttc taacaatacc aatagctagg acccggctgc tgtgcactgg
1620gactggggat tccacatgtt tgccttggga gtctcaagct ggactgcca
1669713071DNAArtificial SequenceOPA1-ND4-3'UTR 71gtgctgcccg cctagaaagg
gtgaagtggt tgtttccgtg acggactgag tacgggtgcc 60tgtcaggctc ttgcggaagt
ccatgcgcca ttgggagggc ctcggccgcg gctctgtgcc 120cttgctgctg agggccactt
cctgggtcat tcctggaccg ggagccgggc tggggctcac 180acgggggctc ccgcgtggcc
gtctcggcgc ctgcgtgacc tccccgccgg cgggatgtgg 240cgactacgtc gggccgctgt
ggcctgatgc taaaactaat cgtcccaaca attatgttac 300taccactgac atggctttcc
aaaaaacaca tgatttggat caacacaacc acccacagcc 360taattattag catcatccct
ctactatttt ttaaccaaat caacaacaac ctatttagct 420gttccccaac cttttcctcc
gaccccctaa caacccccct cctaatgcta actacctggc 480tcctacccct cacaatcatg
gcaagccaac gccacttatc cagtgaacca ctatcacgaa 540aaaaactcta cctctctatg
ctaatctccc tacaaatctc cttaattatg acattcacag 600ccacagaact aatcatgttt
tatatcttct tcgaaaccac acttatcccc accttggcta 660tcatcacccg atggggcaac
cagccagaac gcctgaacgc aggcacatac ttcctattct 720acaccctagt aggctccctt
cccctactca tcgcactaat ttacactcac aacaccctag 780gctcactaaa cattctacta
ctcactctca ctgcccaaga actatcaaac tcctgggcca 840acaacttaat gtggctagct
tacacaatgg cttttatggt aaagatgcct ctttacggac 900tccacttatg gctccctaaa
gcccatgtcg aagcccccat cgctgggtca atggtacttg 960ccgcagtact cttaaaacta
ggcggctatg gtatgatgcg cctcacactc attctcaacc 1020ccctgacaaa acacatggcc
taccccttcc ttgtactatc cctatggggc atgattatga 1080caagctccat ctgcctacga
caaacagacc taaaatcgct cattgcatac tcttcaatca 1140gccacatggc cctcgtagta
acagccattc tcatccaaac cccctggagc ttcaccggcg 1200cagtcattct catgatcgcc
cacgggctta catcctcatt actattctgc ctagcaaact 1260caaactacga acgcactcac
agtcgcatca tgatcctctc tcaaggactt caaactctac 1320tcccactaat ggctttttgg
tggcttctag caagcctcgc taacctcgcc ttacccccca 1380ctattaacct actgggagaa
ctctctgtgc tagtaaccac gttctcctgg tcaaatatca 1440ctctcctact tacaggactc
aacatgctag tcacagccct atactccctc tacatgttta 1500ccacaacaca atggggctca
ctcacccacc acattaacaa catgaaaccc tcattcacac 1560gagaaaacac cctcatgttc
atgcacctat cccccattct cctcctatcc ctcaaccccg 1620acatcattac cgggttttcc
tcttaagagc actgggacgc ccaccgcccc tttccctccg 1680ctgccaggcg agcatgttgt
ggtaattctg gaacacaaga agagaaattg ctgggtttag 1740aacaagatta taaacgaatt
cggtgctcag tgatcacttg acagtttttt ttttttttaa 1800atattaccca aaatgctccc
caaataagaa atgcatcagc tcagtcagtg aatacaaaaa 1860aggaattatt tttccctttg
agggtctttt atacatctct cctccaaccc caccctctat 1920tctgtttctt cctcctcaca
tgggggtaca catacacagc ttcctctttt ggttccatcc 1980ttaccaccac accacacgca
cactccacat gcccagcaga gtggcacttg gtggccagaa 2040agtgtgagcc tcatgatctg
ctgtctgtag ttctgtgagc tcaggtccct caaaggcctc 2100ggagcacccc cttccttgtg
actgagccag ggcctgcatt tttggttttc cccaccccac 2160acattctcaa ccatagtcct
tctaacaata ccaatagcta ggacccggct gctgtgcact 2220gggactgggg attccacatg
tttgccttgg gagtctcaag ctggactgcc agcccctgtc 2280ctcccttcac ccccattgcg
tatgagcatt tcagaactcc aaggagtcac aggcatcttt 2340atagttcacg ttaacatata
gacactgttg gaagcagttc cttctaaaag ggtagccctg 2400gacttaatac cagccggata
cctctggccc ccaccccatt actgtacctc tggagtcact 2460actgtgggtc gccactcctc
tgctacacag cacggctttt tcaaggctgt attgagaagg 2520gaagttagga agaagggtgt
gctgggctaa ccagcccaca gagctcacat tcctgtccct 2580tgggtgaaaa atacatgtcc
atcctgatat ctcctgaatt cagaaattag cctccacatg 2640tgcaatggct ttaagagcca
gaagcagggt tctgggaatt ttgcaagtta cctgtggcca 2700ggtgtggtct cggttaccaa
atacggttac ctgcagcttt ttagtccttt gtgctcccac 2760gggtctacag agtcccatct
gcccaaaggt cttgaagctt gacaggatgt tttcgattac 2820tcagtctccc agggcactac
tggtccgtag gattcgattg gtcggggtag gagagttaaa 2880caacatttaa acagagttct
ctcaaaaatg tctaaaggga ttgtaggtag ataacatcca 2940atcactgttt gcacttatct
gaaatcttcc ctcttggctg cccccaggta tttactgtgg 3000agaacattgc ataggaatgt
ctggaaaaag cttctacaac ttgttacagc cttcacattt 3060gtagaagctt t
3071722271DNAArtificial
SequenceOPA1-ND4-3'UTR* 72gtgctgcccg cctagaaagg gtgaagtggt tgtttccgtg
acggactgag tacgggtgcc 60tgtcaggctc ttgcggaagt ccatgcgcca ttgggagggc
ctcggccgcg gctctgtgcc 120cttgctgctg agggccactt cctgggtcat tcctggaccg
ggagccgggc tggggctcac 180acgggggctc ccgcgtggcc gtctcggcgc ctgcgtgacc
tccccgccgg cgggatgtgg 240cgactacgtc gggccgctgt ggcctgatgc taaaactaat
cgtcccaaca attatgttac 300taccactgac atggctttcc aaaaaacaca tgatttggat
caacacaacc acccacagcc 360taattattag catcatccct ctactatttt ttaaccaaat
caacaacaac ctatttagct 420gttccccaac cttttcctcc gaccccctaa caacccccct
cctaatgcta actacctggc 480tcctacccct cacaatcatg gcaagccaac gccacttatc
cagtgaacca ctatcacgaa 540aaaaactcta cctctctatg ctaatctccc tacaaatctc
cttaattatg acattcacag 600ccacagaact aatcatgttt tatatcttct tcgaaaccac
acttatcccc accttggcta 660tcatcacccg atggggcaac cagccagaac gcctgaacgc
aggcacatac ttcctattct 720acaccctagt aggctccctt cccctactca tcgcactaat
ttacactcac aacaccctag 780gctcactaaa cattctacta ctcactctca ctgcccaaga
actatcaaac tcctgggcca 840acaacttaat gtggctagct tacacaatgg cttttatggt
aaagatgcct ctttacggac 900tccacttatg gctccctaaa gcccatgtcg aagcccccat
cgctgggtca atggtacttg 960ccgcagtact cttaaaacta ggcggctatg gtatgatgcg
cctcacactc attctcaacc 1020ccctgacaaa acacatggcc taccccttcc ttgtactatc
cctatggggc atgattatga 1080caagctccat ctgcctacga caaacagacc taaaatcgct
cattgcatac tcttcaatca 1140gccacatggc cctcgtagta acagccattc tcatccaaac
cccctggagc ttcaccggcg 1200cagtcattct catgatcgcc cacgggctta catcctcatt
actattctgc ctagcaaact 1260caaactacga acgcactcac agtcgcatca tgatcctctc
tcaaggactt caaactctac 1320tcccactaat ggctttttgg tggcttctag caagcctcgc
taacctcgcc ttacccccca 1380ctattaacct actgggagaa ctctctgtgc tagtaaccac
gttctcctgg tcaaatatca 1440ctctcctact tacaggactc aacatgctag tcacagccct
atactccctc tacatgttta 1500ccacaacaca atggggctca ctcacccacc acattaacaa
catgaaaccc tcattcacac 1560gagaaaacac cctcatgttc atgcacctat cccccattct
cctcctatcc ctcaaccccg 1620acatcattac cgggttttcc tcttaagagc actgggacgc
ccaccgcccc tttccctccg 1680ctgccaggcg agcatgttgt ggtaattctg gaacacaaga
agagaaattg ctgggtttag 1740aacaagatta taaacgaatt cggtgctcag tgatcacttg
acagtttttt ttttttttaa 1800atattaccca aaatgctccc caaataagaa atgcatcagc
tcagtcagtg aatacaaaaa 1860aggaattatt tttccctttg agggtctttt atacatctct
cctccaaccc caccctctat 1920tctgtttctt cctcctcaca tgggggtaca catacacagc
ttcctctttt ggttccatcc 1980ttaccaccac accacacgca cactccacat gcccagcaga
gtggcacttg gtggccagaa 2040agtgtgagcc tcatgatctg ctgtctgtag ttctgtgagc
tcaggtccct caaaggcctc 2100ggagcacccc cttccttgtg actgagccag ggcctgcatt
tttggttttc cccaccccac 2160acattctcaa ccatagtcct tctaacaata ccaatagcta
ggacccggct gctgtgcact 2220gggactgggg attccacatg tttgccttgg gagtctcaag
ctggactgcc a 2271733071DNAArtificial
SequenceOPA1-opt_ND4-3'UTR 73gtgctgcccg cctagaaagg gtgaagtggt tgtttccgtg
acggactgag tacgggtgcc 60tgtcaggctc ttgcggaagt ccatgcgcca ttgggagggc
ctcggccgcg gctctgtgcc 120cttgctgctg agggccactt cctgggtcat tcctggaccg
ggagccgggc tggggctcac 180acgggggctc ccgcgtggcc gtctcggcgc ctgcgtgacc
tccccgccgg cgggatgtgg 240cgactacgtc gggccgctgt ggcctgatgc tgaagctgat
cgtgcccacc atcatgctgc 300tgcctctgac ctggctgagc aagaaacaca tgatctggat
caacaccacc acgcacagcc 360tgatcatcag catcatccct ctgctgttct tcaaccagat
caacaacaac ctgttcagct 420gcagccccac cttcagcagc gaccctctga caacacctct
gctgatgctg accacctggc 480tgctgcccct cacaatcatg gcctctcaga gacacctgag
cagcgagccc ctgagccgga 540agaaactgta cctgagcatg ctgatctccc tgcagatctc
tctgatcatg accttcaccg 600ccaccgagct gatcatgttc tacatctttt tcgagacaac
gctgatcccc acactggcca 660tcatcaccag atggggcaac cagcctgaga gactgaacgc
cggcacctac tttctgttct 720acaccctcgt gggcagcctg ccactgctga ttgccctgat
ctacacccac aacaccctgg 780gctccctgaa catcctgctg ctgacactga cagcccaaga
gctgagcaac agctgggcca 840acaatctgat gtggctggcc tacacaatgg ccttcatggt
caagatgccc ctgtacggcc 900tgcacctgtg gctgcctaaa gctcatgtgg aagcccctat
cgccggctct atggtgctgg 960ctgcagtgct gctgaaactc ggcggctacg gcatgatgcg
gctgaccctg attctgaatc 1020ccctgaccaa gcacatggcc tatccatttc tggtgctgag
cctgtggggc atgattatga 1080ccagcagcat ctgcctgcgg cagaccgatc tgaagtccct
gatcgcctac agctccatca 1140gccacatggc cctggtggtc accgccatcc tgattcagac
cccttggagc tttacaggcg 1200ccgtgatcct gatgattgcc cacggcctga caagcagcct
gctgttttgt ctggccaaca 1260gcaactacga gcggacccac agcagaatca tgatcctgtc
tcagggcctg cagaccctcc 1320tgcctcttat ggctttttgg tggctgctgg cctctctggc
caatctggca ctgcctccta 1380ccatcaatct gctgggcgag ctgagcgtgc tggtcaccac
attcagctgg tccaatatca 1440ccctgctgct caccggcctg aacatgctgg ttacagccct
gtactccctg tacatgttca 1500ccaccacaca gtggggaagc ctgacacacc acatcaacaa
tatgaagccc agcttcaccc 1560gcgagaacac cctgatgttc atgcatctga gccccattct
gctgctgtcc ctgaatcctg 1620atatcatcac cggcttctcc agctgagagc actgggacgc
ccaccgcccc tttccctccg 1680ctgccaggcg agcatgttgt ggtaattctg gaacacaaga
agagaaattg ctgggtttag 1740aacaagatta taaacgaatt cggtgctcag tgatcacttg
acagtttttt ttttttttaa 1800atattaccca aaatgctccc caaataagaa atgcatcagc
tcagtcagtg aatacaaaaa 1860aggaattatt tttccctttg agggtctttt atacatctct
cctccaaccc caccctctat 1920tctgtttctt cctcctcaca tgggggtaca catacacagc
ttcctctttt ggttccatcc 1980ttaccaccac accacacgca cactccacat gcccagcaga
gtggcacttg gtggccagaa 2040agtgtgagcc tcatgatctg ctgtctgtag ttctgtgagc
tcaggtccct caaaggcctc 2100ggagcacccc cttccttgtg actgagccag ggcctgcatt
tttggttttc cccaccccac 2160acattctcaa ccatagtcct tctaacaata ccaatagcta
ggacccggct gctgtgcact 2220gggactgggg attccacatg tttgccttgg gagtctcaag
ctggactgcc agcccctgtc 2280ctcccttcac ccccattgcg tatgagcatt tcagaactcc
aaggagtcac aggcatcttt 2340atagttcacg ttaacatata gacactgttg gaagcagttc
cttctaaaag ggtagccctg 2400gacttaatac cagccggata cctctggccc ccaccccatt
actgtacctc tggagtcact 2460actgtgggtc gccactcctc tgctacacag cacggctttt
tcaaggctgt attgagaagg 2520gaagttagga agaagggtgt gctgggctaa ccagcccaca
gagctcacat tcctgtccct 2580tgggtgaaaa atacatgtcc atcctgatat ctcctgaatt
cagaaattag cctccacatg 2640tgcaatggct ttaagagcca gaagcagggt tctgggaatt
ttgcaagtta cctgtggcca 2700ggtgtggtct cggttaccaa atacggttac ctgcagcttt
ttagtccttt gtgctcccac 2760gggtctacag agtcccatct gcccaaaggt cttgaagctt
gacaggatgt tttcgattac 2820tcagtctccc agggcactac tggtccgtag gattcgattg
gtcggggtag gagagttaaa 2880caacatttaa acagagttct ctcaaaaatg tctaaaggga
ttgtaggtag ataacatcca 2940atcactgttt gcacttatct gaaatcttcc ctcttggctg
cccccaggta tttactgtgg 3000agaacattgc ataggaatgt ctggaaaaag cttctacaac
ttgttacagc cttcacattt 3060gtagaagctt t
3071742271DNAArtificial SequenceOPA1-opt_ND4-3'UTR*
74gtgctgcccg cctagaaagg gtgaagtggt tgtttccgtg acggactgag tacgggtgcc
60tgtcaggctc ttgcggaagt ccatgcgcca ttgggagggc ctcggccgcg gctctgtgcc
120cttgctgctg agggccactt cctgggtcat tcctggaccg ggagccgggc tggggctcac
180acgggggctc ccgcgtggcc gtctcggcgc ctgcgtgacc tccccgccgg cgggatgtgg
240cgactacgtc gggccgctgt ggcctgatgc tgaagctgat cgtgcccacc atcatgctgc
300tgcctctgac ctggctgagc aagaaacaca tgatctggat caacaccacc acgcacagcc
360tgatcatcag catcatccct ctgctgttct tcaaccagat caacaacaac ctgttcagct
420gcagccccac cttcagcagc gaccctctga caacacctct gctgatgctg accacctggc
480tgctgcccct cacaatcatg gcctctcaga gacacctgag cagcgagccc ctgagccgga
540agaaactgta cctgagcatg ctgatctccc tgcagatctc tctgatcatg accttcaccg
600ccaccgagct gatcatgttc tacatctttt tcgagacaac gctgatcccc acactggcca
660tcatcaccag atggggcaac cagcctgaga gactgaacgc cggcacctac tttctgttct
720acaccctcgt gggcagcctg ccactgctga ttgccctgat ctacacccac aacaccctgg
780gctccctgaa catcctgctg ctgacactga cagcccaaga gctgagcaac agctgggcca
840acaatctgat gtggctggcc tacacaatgg ccttcatggt caagatgccc ctgtacggcc
900tgcacctgtg gctgcctaaa gctcatgtgg aagcccctat cgccggctct atggtgctgg
960ctgcagtgct gctgaaactc ggcggctacg gcatgatgcg gctgaccctg attctgaatc
1020ccctgaccaa gcacatggcc tatccatttc tggtgctgag cctgtggggc atgattatga
1080ccagcagcat ctgcctgcgg cagaccgatc tgaagtccct gatcgcctac agctccatca
1140gccacatggc cctggtggtc accgccatcc tgattcagac cccttggagc tttacaggcg
1200ccgtgatcct gatgattgcc cacggcctga caagcagcct gctgttttgt ctggccaaca
1260gcaactacga gcggacccac agcagaatca tgatcctgtc tcagggcctg cagaccctcc
1320tgcctcttat ggctttttgg tggctgctgg cctctctggc caatctggca ctgcctccta
1380ccatcaatct gctgggcgag ctgagcgtgc tggtcaccac attcagctgg tccaatatca
1440ccctgctgct caccggcctg aacatgctgg ttacagccct gtactccctg tacatgttca
1500ccaccacaca gtggggaagc ctgacacacc acatcaacaa tatgaagccc agcttcaccc
1560gcgagaacac cctgatgttc atgcatctga gccccattct gctgctgtcc ctgaatcctg
1620atatcatcac cggcttctcc agctgagagc actgggacgc ccaccgcccc tttccctccg
1680ctgccaggcg agcatgttgt ggtaattctg gaacacaaga agagaaattg ctgggtttag
1740aacaagatta taaacgaatt cggtgctcag tgatcacttg acagtttttt ttttttttaa
1800atattaccca aaatgctccc caaataagaa atgcatcagc tcagtcagtg aatacaaaaa
1860aggaattatt tttccctttg agggtctttt atacatctct cctccaaccc caccctctat
1920tctgtttctt cctcctcaca tgggggtaca catacacagc ttcctctttt ggttccatcc
1980ttaccaccac accacacgca cactccacat gcccagcaga gtggcacttg gtggccagaa
2040agtgtgagcc tcatgatctg ctgtctgtag ttctgtgagc tcaggtccct caaaggcctc
2100ggagcacccc cttccttgtg actgagccag ggcctgcatt tttggttttc cccaccccac
2160acattctcaa ccatagtcct tctaacaata ccaatagcta ggacccggct gctgtgcact
2220gggactgggg attccacatg tttgccttgg gagtctcaag ctggactgcc a
2271753071DNAArtificial SequenceOPA1-opt_ND4*-3'UTR 75gtgctgcccg
cctagaaagg gtgaagtggt tgtttccgtg acggactgag tacgggtgcc 60tgtcaggctc
ttgcggaagt ccatgcgcca ttgggagggc ctcggccgcg gctctgtgcc 120cttgctgctg
agggccactt cctgggtcat tcctggaccg ggagccgggc tggggctcac 180acgggggctc
ccgcgtggcc gtctcggcgc ctgcgtgacc tccccgccgg cgggatgtgg 240cgactacgtc
gggccgctgt ggcctgatgc tgaagctgat cgtgcccacc atcatgctgc 300tgcccctgac
ctggctgagc aagaagcaca tgatctggat caacaccacc acccacagcc 360tgatcatcag
catcatcccc ctgctgttct tcaaccagat caacaacaac ctgttcagct 420gcagccccac
cttcagcagc gaccccctga ccacccccct gctgatgctg accacctggc 480tgctgcccct
gaccatcatg gccagccagc gccacctgag cagcgagccc ctgagccgca 540agaagctgta
cctgagcatg ctgatcagcc tgcagatcag cctgatcatg accttcaccg 600ccaccgagct
gatcatgttc tacatcttct tcgagaccac cctgatcccc accctggcca 660tcatcacccg
ctggggcaac cagcccgagc gcctgaacgc cggcacctac ttcctgttct 720acaccctggt
gggcagcctg cccctgctga tcgccctgat ctacacccac aacaccctgg 780gcagcctgaa
catcctgctg ctgaccctga ccgcccagga gctgagcaac agctgggcca 840acaacctgat
gtggctggcc tacaccatgg ccttcatggt gaagatgccc ctgtacggcc 900tgcacctgtg
gctgcccaag gcccacgtgg aggcccccat cgccggcagc atggtgctgg 960ccgccgtgct
gctgaagctg ggcggctacg gcatgatgcg cctgaccctg atcctgaacc 1020ccctgaccaa
gcacatggcc taccccttcc tggtgctgag cctgtggggc atgatcatga 1080ccagcagcat
ctgcctgcgc cagaccgacc tgaagagcct gatcgcctac agcagcatca 1140gccacatggc
cctggtggtg accgccatcc tgatccagac cccctggagc ttcaccggcg 1200ccgtgatcct
gatgatcgcc cacggcctga ccagcagcct gctgttctgc ctggccaaca 1260gcaactacga
gcgcacccac agccgcatca tgatcctgag ccagggcctg cagaccctgc 1320tgcccctgat
ggccttctgg tggctgctgg ccagcctggc caacctggcc ctgcccccca 1380ccatcaacct
gctgggcgag ctgagcgtgc tggtgaccac cttcagctgg agcaacatca 1440ccctgctgct
gaccggcctg aacatgctgg tgaccgccct gtacagcctg tacatgttca 1500ccaccaccca
gtggggcagc ctgacccacc acatcaacaa catgaagccc agcttcaccc 1560gcgagaacac
cctgatgttc atgcacctga gccccatcct gctgctgagc ctgaaccccg 1620acatcatcac
cggcttcagc agctaagagc actgggacgc ccaccgcccc tttccctccg 1680ctgccaggcg
agcatgttgt ggtaattctg gaacacaaga agagaaattg ctgggtttag 1740aacaagatta
taaacgaatt cggtgctcag tgatcacttg acagtttttt ttttttttaa 1800atattaccca
aaatgctccc caaataagaa atgcatcagc tcagtcagtg aatacaaaaa 1860aggaattatt
tttccctttg agggtctttt atacatctct cctccaaccc caccctctat 1920tctgtttctt
cctcctcaca tgggggtaca catacacagc ttcctctttt ggttccatcc 1980ttaccaccac
accacacgca cactccacat gcccagcaga gtggcacttg gtggccagaa 2040agtgtgagcc
tcatgatctg ctgtctgtag ttctgtgagc tcaggtccct caaaggcctc 2100ggagcacccc
cttccttgtg actgagccag ggcctgcatt tttggttttc cccaccccac 2160acattctcaa
ccatagtcct tctaacaata ccaatagcta ggacccggct gctgtgcact 2220gggactgggg
attccacatg tttgccttgg gagtctcaag ctggactgcc agcccctgtc 2280ctcccttcac
ccccattgcg tatgagcatt tcagaactcc aaggagtcac aggcatcttt 2340atagttcacg
ttaacatata gacactgttg gaagcagttc cttctaaaag ggtagccctg 2400gacttaatac
cagccggata cctctggccc ccaccccatt actgtacctc tggagtcact 2460actgtgggtc
gccactcctc tgctacacag cacggctttt tcaaggctgt attgagaagg 2520gaagttagga
agaagggtgt gctgggctaa ccagcccaca gagctcacat tcctgtccct 2580tgggtgaaaa
atacatgtcc atcctgatat ctcctgaatt cagaaattag cctccacatg 2640tgcaatggct
ttaagagcca gaagcagggt tctgggaatt ttgcaagtta cctgtggcca 2700ggtgtggtct
cggttaccaa atacggttac ctgcagcttt ttagtccttt gtgctcccac 2760gggtctacag
agtcccatct gcccaaaggt cttgaagctt gacaggatgt tttcgattac 2820tcagtctccc
agggcactac tggtccgtag gattcgattg gtcggggtag gagagttaaa 2880caacatttaa
acagagttct ctcaaaaatg tctaaaggga ttgtaggtag ataacatcca 2940atcactgttt
gcacttatct gaaatcttcc ctcttggctg cccccaggta tttactgtgg 3000agaacattgc
ataggaatgt ctggaaaaag cttctacaac ttgttacagc cttcacattt 3060gtagaagctt t
3071762271DNAArtificial SequenceOPA1-opt_ND4*-3'UTR* 76gtgctgcccg
cctagaaagg gtgaagtggt tgtttccgtg acggactgag tacgggtgcc 60tgtcaggctc
ttgcggaagt ccatgcgcca ttgggagggc ctcggccgcg gctctgtgcc 120cttgctgctg
agggccactt cctgggtcat tcctggaccg ggagccgggc tggggctcac 180acgggggctc
ccgcgtggcc gtctcggcgc ctgcgtgacc tccccgccgg cgggatgtgg 240cgactacgtc
gggccgctgt ggcctgatgc tgaagctgat cgtgcccacc atcatgctgc 300tgcccctgac
ctggctgagc aagaagcaca tgatctggat caacaccacc acccacagcc 360tgatcatcag
catcatcccc ctgctgttct tcaaccagat caacaacaac ctgttcagct 420gcagccccac
cttcagcagc gaccccctga ccacccccct gctgatgctg accacctggc 480tgctgcccct
gaccatcatg gccagccagc gccacctgag cagcgagccc ctgagccgca 540agaagctgta
cctgagcatg ctgatcagcc tgcagatcag cctgatcatg accttcaccg 600ccaccgagct
gatcatgttc tacatcttct tcgagaccac cctgatcccc accctggcca 660tcatcacccg
ctggggcaac cagcccgagc gcctgaacgc cggcacctac ttcctgttct 720acaccctggt
gggcagcctg cccctgctga tcgccctgat ctacacccac aacaccctgg 780gcagcctgaa
catcctgctg ctgaccctga ccgcccagga gctgagcaac agctgggcca 840acaacctgat
gtggctggcc tacaccatgg ccttcatggt gaagatgccc ctgtacggcc 900tgcacctgtg
gctgcccaag gcccacgtgg aggcccccat cgccggcagc atggtgctgg 960ccgccgtgct
gctgaagctg ggcggctacg gcatgatgcg cctgaccctg atcctgaacc 1020ccctgaccaa
gcacatggcc taccccttcc tggtgctgag cctgtggggc atgatcatga 1080ccagcagcat
ctgcctgcgc cagaccgacc tgaagagcct gatcgcctac agcagcatca 1140gccacatggc
cctggtggtg accgccatcc tgatccagac cccctggagc ttcaccggcg 1200ccgtgatcct
gatgatcgcc cacggcctga ccagcagcct gctgttctgc ctggccaaca 1260gcaactacga
gcgcacccac agccgcatca tgatcctgag ccagggcctg cagaccctgc 1320tgcccctgat
ggccttctgg tggctgctgg ccagcctggc caacctggcc ctgcccccca 1380ccatcaacct
gctgggcgag ctgagcgtgc tggtgaccac cttcagctgg agcaacatca 1440ccctgctgct
gaccggcctg aacatgctgg tgaccgccct gtacagcctg tacatgttca 1500ccaccaccca
gtggggcagc ctgacccacc acatcaacaa catgaagccc agcttcaccc 1560gcgagaacac
cctgatgttc atgcacctga gccccatcct gctgctgagc ctgaaccccg 1620acatcatcac
cggcttcagc agctaagagc actgggacgc ccaccgcccc tttccctccg 1680ctgccaggcg
agcatgttgt ggtaattctg gaacacaaga agagaaattg ctgggtttag 1740aacaagatta
taaacgaatt cggtgctcag tgatcacttg acagtttttt ttttttttaa 1800atattaccca
aaatgctccc caaataagaa atgcatcagc tcagtcagtg aatacaaaaa 1860aggaattatt
tttccctttg agggtctttt atacatctct cctccaaccc caccctctat 1920tctgtttctt
cctcctcaca tgggggtaca catacacagc ttcctctttt ggttccatcc 1980ttaccaccac
accacacgca cactccacat gcccagcaga gtggcacttg gtggccagaa 2040agtgtgagcc
tcatgatctg ctgtctgtag ttctgtgagc tcaggtccct caaaggcctc 2100ggagcacccc
cttccttgtg actgagccag ggcctgcatt tttggttttc cccaccccac 2160acattctcaa
ccatagtcct tctaacaata ccaatagcta ggacccggct gctgtgcact 2220gggactgggg
attccacatg tttgccttgg gagtctcaag ctggactgcc a
2271772216DNAArtificial SequenceOPA1-ND6-3'UTR 77gtgctgcccg cctagaaagg
gtgaagtggt tgtttccgtg acggactgag tacgggtgcc 60tgtcaggctc ttgcggaagt
ccatgcgcca ttgggagggc ctcggccgcg gctctgtgcc 120cttgctgctg agggccactt
cctgggtcat tcctggaccg ggagccgggc tggggctcac 180acgggggctc ccgcgtggcc
gtctcggcgc ctgcgtgacc tccccgccgg cgggatgtgg 240cgactacgtc gggccgctgt
ggcctgatga tgtatgcttt gtttctgttg agtgtgggtt 300tagtaatggg gtttgtgggg
ttttcttcta agccttctcc tatttatggg ggtttagtat 360tgattgttag cggtgtggtc
gggtgtgtta ttattctgaa ttttggggga ggttatatgg 420gtttaatggt ttttttaatt
tatttagggg gaatgatggt tgtctttgga tatactacag 480cgatggctat tgaggagtat
cctgaggcat gggggtcagg ggttgaggtc ttggtgagtg 540ttttagtggg gttagcgatg
gaggtaggat tggtgctgtg ggtgaaagag tatgatgggg 600tggtggttgt ggtaaacttt
aatagtgtag gaagctggat gatttatgaa ggagaggggt 660cagggttgat tcgggaggat
cctattggtg cgggggcttt gtatgattat gggcgttggt 720tagtagtagt tactggttgg
acattgtttg ttggtgtata tattgtaatt gagattgctc 780gggggaatta ggagcactgg
gacgcccacc gcccctttcc ctccgctgcc aggcgagcat 840gttgtggtaa ttctggaaca
caagaagaga aattgctggg tttagaacaa gattataaac 900gaattcggtg ctcagtgatc
acttgacagt tttttttttt tttaaatatt acccaaaatg 960ctccccaaat aagaaatgca
tcagctcagt cagtgaatac aaaaaaggaa ttatttttcc 1020ctttgagggt cttttataca
tctctcctcc aaccccaccc tctattctgt ttcttcctcc 1080tcacatgggg gtacacatac
acagcttcct cttttggttc catccttacc accacaccac 1140acgcacactc cacatgccca
gcagagtggc acttggtggc cagaaagtgt gagcctcatg 1200atctgctgtc tgtagttctg
tgagctcagg tccctcaaag gcctcggagc acccccttcc 1260ttgtgactga gccagggcct
gcatttttgg ttttccccac cccacacatt ctcaaccata 1320gtccttctaa caataccaat
agctaggacc cggctgctgt gcactgggac tggggattcc 1380acatgtttgc cttgggagtc
tcaagctgga ctgccagccc ctgtcctccc ttcaccccca 1440ttgcgtatga gcatttcaga
actccaagga gtcacaggca tctttatagt tcacgttaac 1500atatagacac tgttggaagc
agttccttct aaaagggtag ccctggactt aataccagcc 1560ggatacctct ggcccccacc
ccattactgt acctctggag tcactactgt gggtcgccac 1620tcctctgcta cacagcacgg
ctttttcaag gctgtattga gaagggaagt taggaagaag 1680ggtgtgctgg gctaaccagc
ccacagagct cacattcctg tcccttgggt gaaaaataca 1740tgtccatcct gatatctcct
gaattcagaa attagcctcc acatgtgcaa tggctttaag 1800agccagaagc agggttctgg
gaattttgca agttacctgt ggccaggtgt ggtctcggtt 1860accaaatacg gttacctgca
gctttttagt cctttgtgct cccacgggtc tacagagtcc 1920catctgccca aaggtcttga
agcttgacag gatgttttcg attactcagt ctcccagggc 1980actactggtc cgtaggattc
gattggtcgg ggtaggagag ttaaacaaca tttaaacaga 2040gttctctcaa aaatgtctaa
agggattgta ggtagataac atccaatcac tgtttgcact 2100tatctgaaat cttccctctt
ggctgccccc aggtatttac tgtggagaac attgcatagg 2160aatgtctgga aaaagcttct
acaacttgtt acagccttca catttgtaga agcttt 2216781416DNAArtificial
SequenceOPA1-ND6-3'UTR* 78gtgctgcccg cctagaaagg gtgaagtggt tgtttccgtg
acggactgag tacgggtgcc 60tgtcaggctc ttgcggaagt ccatgcgcca ttgggagggc
ctcggccgcg gctctgtgcc 120cttgctgctg agggccactt cctgggtcat tcctggaccg
ggagccgggc tggggctcac 180acgggggctc ccgcgtggcc gtctcggcgc ctgcgtgacc
tccccgccgg cgggatgtgg 240cgactacgtc gggccgctgt ggcctgatga tgtatgcttt
gtttctgttg agtgtgggtt 300tagtaatggg gtttgtgggg ttttcttcta agccttctcc
tatttatggg ggtttagtat 360tgattgttag cggtgtggtc gggtgtgtta ttattctgaa
ttttggggga ggttatatgg 420gtttaatggt ttttttaatt tatttagggg gaatgatggt
tgtctttgga tatactacag 480cgatggctat tgaggagtat cctgaggcat gggggtcagg
ggttgaggtc ttggtgagtg 540ttttagtggg gttagcgatg gaggtaggat tggtgctgtg
ggtgaaagag tatgatgggg 600tggtggttgt ggtaaacttt aatagtgtag gaagctggat
gatttatgaa ggagaggggt 660cagggttgat tcgggaggat cctattggtg cgggggcttt
gtatgattat gggcgttggt 720tagtagtagt tactggttgg acattgtttg ttggtgtata
tattgtaatt gagattgctc 780gggggaatta ggagcactgg gacgcccacc gcccctttcc
ctccgctgcc aggcgagcat 840gttgtggtaa ttctggaaca caagaagaga aattgctggg
tttagaacaa gattataaac 900gaattcggtg ctcagtgatc acttgacagt tttttttttt
tttaaatatt acccaaaatg 960ctccccaaat aagaaatgca tcagctcagt cagtgaatac
aaaaaaggaa ttatttttcc 1020ctttgagggt cttttataca tctctcctcc aaccccaccc
tctattctgt ttcttcctcc 1080tcacatgggg gtacacatac acagcttcct cttttggttc
catccttacc accacaccac 1140acgcacactc cacatgccca gcagagtggc acttggtggc
cagaaagtgt gagcctcatg 1200atctgctgtc tgtagttctg tgagctcagg tccctcaaag
gcctcggagc acccccttcc 1260ttgtgactga gccagggcct gcatttttgg ttttccccac
cccacacatt ctcaaccata 1320gtccttctaa caataccaat agctaggacc cggctgctgt
gcactgggac tggggattcc 1380acatgtttgc cttgggagtc tcaagctgga ctgcca
1416792216DNAArtificial SequenceOPA1-opt_ND6-3'UTR
79gtgctgcccg cctagaaagg gtgaagtggt tgtttccgtg acggactgag tacgggtgcc
60tgtcaggctc ttgcggaagt ccatgcgcca ttgggagggc ctcggccgcg gctctgtgcc
120cttgctgctg agggccactt cctgggtcat tcctggaccg ggagccgggc tggggctcac
180acgggggctc ccgcgtggcc gtctcggcgc ctgcgtgacc tccccgccgg cgggatgtgg
240cgactacgtc gggccgctgt ggcctgatga tgtacgccct gttcctgctg agcgtgggcc
300tggtgatggg cttcgtgggc ttcagcagca agcccagccc catctacggc ggcctggtgc
360tgatcgtgag cggcgtggtg ggctgcgtga tcatcctgaa cttcggcggc ggctacatgg
420gcctgatggt gttcctgatc tacctgggcg gcatgatggt ggtgttcggc tacaccaccg
480ccatggccat cgaggagtac cccgaggcct ggggcagcgg cgtggaggtg ctggtgagcg
540tgctggtggg cctggccatg gaggtgggcc tggtgctgtg ggtgaaggag tacgacggcg
600tggtggtggt ggtgaacttc aacagcgtgg gcagctggat gatctacgag ggcgagggca
660gcggcctgat ccgcgaggac cccatcggcg ccggcgccct gtacgactac ggccgctggc
720tggtggtggt gaccggctgg accctgttcg tgggcgtgta catcgtgatc gagatcgccc
780gcggcaacta agagcactgg gacgcccacc gcccctttcc ctccgctgcc aggcgagcat
840gttgtggtaa ttctggaaca caagaagaga aattgctggg tttagaacaa gattataaac
900gaattcggtg ctcagtgatc acttgacagt tttttttttt tttaaatatt acccaaaatg
960ctccccaaat aagaaatgca tcagctcagt cagtgaatac aaaaaaggaa ttatttttcc
1020ctttgagggt cttttataca tctctcctcc aaccccaccc tctattctgt ttcttcctcc
1080tcacatgggg gtacacatac acagcttcct cttttggttc catccttacc accacaccac
1140acgcacactc cacatgccca gcagagtggc acttggtggc cagaaagtgt gagcctcatg
1200atctgctgtc tgtagttctg tgagctcagg tccctcaaag gcctcggagc acccccttcc
1260ttgtgactga gccagggcct gcatttttgg ttttccccac cccacacatt ctcaaccata
1320gtccttctaa caataccaat agctaggacc cggctgctgt gcactgggac tggggattcc
1380acatgtttgc cttgggagtc tcaagctgga ctgccagccc ctgtcctccc ttcaccccca
1440ttgcgtatga gcatttcaga actccaagga gtcacaggca tctttatagt tcacgttaac
1500atatagacac tgttggaagc agttccttct aaaagggtag ccctggactt aataccagcc
1560ggatacctct ggcccccacc ccattactgt acctctggag tcactactgt gggtcgccac
1620tcctctgcta cacagcacgg ctttttcaag gctgtattga gaagggaagt taggaagaag
1680ggtgtgctgg gctaaccagc ccacagagct cacattcctg tcccttgggt gaaaaataca
1740tgtccatcct gatatctcct gaattcagaa attagcctcc acatgtgcaa tggctttaag
1800agccagaagc agggttctgg gaattttgca agttacctgt ggccaggtgt ggtctcggtt
1860accaaatacg gttacctgca gctttttagt cctttgtgct cccacgggtc tacagagtcc
1920catctgccca aaggtcttga agcttgacag gatgttttcg attactcagt ctcccagggc
1980actactggtc cgtaggattc gattggtcgg ggtaggagag ttaaacaaca tttaaacaga
2040gttctctcaa aaatgtctaa agggattgta ggtagataac atccaatcac tgtttgcact
2100tatctgaaat cttccctctt ggctgccccc aggtatttac tgtggagaac attgcatagg
2160aatgtctgga aaaagcttct acaacttgtt acagccttca catttgtaga agcttt
2216801416DNAArtificial SequenceOPA1-opt_ND6-3'UTR* 80gtgctgcccg
cctagaaagg gtgaagtggt tgtttccgtg acggactgag tacgggtgcc 60tgtcaggctc
ttgcggaagt ccatgcgcca ttgggagggc ctcggccgcg gctctgtgcc 120cttgctgctg
agggccactt cctgggtcat tcctggaccg ggagccgggc tggggctcac 180acgggggctc
ccgcgtggcc gtctcggcgc ctgcgtgacc tccccgccgg cgggatgtgg 240cgactacgtc
gggccgctgt ggcctgatga tgtacgccct gttcctgctg agcgtgggcc 300tggtgatggg
cttcgtgggc ttcagcagca agcccagccc catctacggc ggcctggtgc 360tgatcgtgag
cggcgtggtg ggctgcgtga tcatcctgaa cttcggcggc ggctacatgg 420gcctgatggt
gttcctgatc tacctgggcg gcatgatggt ggtgttcggc tacaccaccg 480ccatggccat
cgaggagtac cccgaggcct ggggcagcgg cgtggaggtg ctggtgagcg 540tgctggtggg
cctggccatg gaggtgggcc tggtgctgtg ggtgaaggag tacgacggcg 600tggtggtggt
ggtgaacttc aacagcgtgg gcagctggat gatctacgag ggcgagggca 660gcggcctgat
ccgcgaggac cccatcggcg ccggcgccct gtacgactac ggccgctggc 720tggtggtggt
gaccggctgg accctgttcg tgggcgtgta catcgtgatc gagatcgccc 780gcggcaacta
agagcactgg gacgcccacc gcccctttcc ctccgctgcc aggcgagcat 840gttgtggtaa
ttctggaaca caagaagaga aattgctggg tttagaacaa gattataaac 900gaattcggtg
ctcagtgatc acttgacagt tttttttttt tttaaatatt acccaaaatg 960ctccccaaat
aagaaatgca tcagctcagt cagtgaatac aaaaaaggaa ttatttttcc 1020ctttgagggt
cttttataca tctctcctcc aaccccaccc tctattctgt ttcttcctcc 1080tcacatgggg
gtacacatac acagcttcct cttttggttc catccttacc accacaccac 1140acgcacactc
cacatgccca gcagagtggc acttggtggc cagaaagtgt gagcctcatg 1200atctgctgtc
tgtagttctg tgagctcagg tccctcaaag gcctcggagc acccccttcc 1260ttgtgactga
gccagggcct gcatttttgg ttttccccac cccacacatt ctcaaccata 1320gtccttctaa
caataccaat agctaggacc cggctgctgt gcactgggac tggggattcc 1380acatgtttgc
cttgggagtc tcaagctgga ctgcca
1416812648DNAArtificial SequenceOPA1-ND1-3'UTR 81gtgctgcccg cctagaaagg
gtgaagtggt tgtttccgtg acggactgag tacgggtgcc 60tgtcaggctc ttgcggaagt
ccatgcgcca ttgggagggc ctcggccgcg gctctgtgcc 120cttgctgctg agggccactt
cctgggtcat tcctggaccg ggagccgggc tggggctcac 180acgggggctc ccgcgtggcc
gtctcggcgc ctgcgtgacc tccccgccgg cgggatgtgg 240cgactacgtc gggccgctgt
ggcctgatgc ccatggccaa cctcctactc ctcattgtac 300ccattctaat cgcaatggca
ttcctaatgc ttaccgaacg aaaaattcta ggctatatgc 360aactacgcaa aggccccaac
gttgtaggcc cctacgggct actacaaccc ttcgctgacg 420ccatgaaact cttcaccaaa
gagcccctaa aacccgccac atctaccatc accctctaca 480tcaccgcccc gaccttagct
ctcaccatcg ctcttctact atggaccccc ctccccatgc 540ccaaccccct ggtcaacctc
aacctaggcc tcctatttat tctagccacc tctagcctag 600ccgtttactc aatcctctgg
tcagggtggg catcaaactc aaactacgcc ctgatcggcg 660cactgcgagc agtagcccaa
acaatctcat atgaagtcac cctagccatc attctactat 720caacattact aatgagtggc
tcctttaacc tctccaccct tatcacaaca caagaacacc 780tctggttact cctgccatca
tggcccttgg ccatgatgtg gtttatctcc acactagcag 840agaccaaccg aacccccttc
gaccttgccg aaggggagtc cgaactagtc tcaggcttca 900acatcgaata cgccgcaggc
cccttcgccc tattcttcat ggccgaatac acaaacatta 960ttatgatgaa caccctcacc
actacaatct tcctaggaac aacatatgac gcactctccc 1020ctgaactcta cacaacatat
tttgtcacca agaccctact tctaacctcc ctgttcttat 1080ggattcgaac agcatacccc
cgattccgct acgaccaact catgcacctc ctatggaaaa 1140acttcctacc actcacccta
gcattactta tgtggtatgt ctccatgccc attacaatct 1200ccagcattcc ccctcaaacc
taagagcact gggacgccca ccgccccttt ccctccgctg 1260ccaggcgagc atgttgtggt
aattctggaa cacaagaaga gaaattgctg ggtttagaac 1320aagattataa acgaattcgg
tgctcagtga tcacttgaca gttttttttt tttttaaata 1380ttacccaaaa tgctccccaa
ataagaaatg catcagctca gtcagtgaat acaaaaaagg 1440aattattttt ccctttgagg
gtcttttata catctctcct ccaaccccac cctctattct 1500gtttcttcct cctcacatgg
gggtacacat acacagcttc ctcttttggt tccatcctta 1560ccaccacacc acacgcacac
tccacatgcc cagcagagtg gcacttggtg gccagaaagt 1620gtgagcctca tgatctgctg
tctgtagttc tgtgagctca ggtccctcaa aggcctcgga 1680gcaccccctt ccttgtgact
gagccagggc ctgcattttt ggttttcccc accccacaca 1740ttctcaacca tagtccttct
aacaatacca atagctagga cccggctgct gtgcactggg 1800actggggatt ccacatgttt
gccttgggag tctcaagctg gactgccagc ccctgtcctc 1860ccttcacccc cattgcgtat
gagcatttca gaactccaag gagtcacagg catctttata 1920gttcacgtta acatatagac
actgttggaa gcagttcctt ctaaaagggt agccctggac 1980ttaataccag ccggatacct
ctggccccca ccccattact gtacctctgg agtcactact 2040gtgggtcgcc actcctctgc
tacacagcac ggctttttca aggctgtatt gagaagggaa 2100gttaggaaga agggtgtgct
gggctaacca gcccacagag ctcacattcc tgtcccttgg 2160gtgaaaaata catgtccatc
ctgatatctc ctgaattcag aaattagcct ccacatgtgc 2220aatggcttta agagccagaa
gcagggttct gggaattttg caagttacct gtggccaggt 2280gtggtctcgg ttaccaaata
cggttacctg cagcttttta gtcctttgtg ctcccacggg 2340tctacagagt cccatctgcc
caaaggtctt gaagcttgac aggatgtttt cgattactca 2400gtctcccagg gcactactgg
tccgtaggat tcgattggtc ggggtaggag agttaaacaa 2460catttaaaca gagttctctc
aaaaatgtct aaagggattg taggtagata acatccaatc 2520actgtttgca cttatctgaa
atcttccctc ttggctgccc ccaggtattt actgtggaga 2580acattgcata ggaatgtctg
gaaaaagctt ctacaacttg ttacagcctt cacatttgta 2640gaagcttt
2648821848DNAArtificial
SequenceOPA1-ND1-3'UTR* 82gtgctgcccg cctagaaagg gtgaagtggt tgtttccgtg
acggactgag tacgggtgcc 60tgtcaggctc ttgcggaagt ccatgcgcca ttgggagggc
ctcggccgcg gctctgtgcc 120cttgctgctg agggccactt cctgggtcat tcctggaccg
ggagccgggc tggggctcac 180acgggggctc ccgcgtggcc gtctcggcgc ctgcgtgacc
tccccgccgg cgggatgtgg 240cgactacgtc gggccgctgt ggcctgatgc ccatggccaa
cctcctactc ctcattgtac 300ccattctaat cgcaatggca ttcctaatgc ttaccgaacg
aaaaattcta ggctatatgc 360aactacgcaa aggccccaac gttgtaggcc cctacgggct
actacaaccc ttcgctgacg 420ccatgaaact cttcaccaaa gagcccctaa aacccgccac
atctaccatc accctctaca 480tcaccgcccc gaccttagct ctcaccatcg ctcttctact
atggaccccc ctccccatgc 540ccaaccccct ggtcaacctc aacctaggcc tcctatttat
tctagccacc tctagcctag 600ccgtttactc aatcctctgg tcagggtggg catcaaactc
aaactacgcc ctgatcggcg 660cactgcgagc agtagcccaa acaatctcat atgaagtcac
cctagccatc attctactat 720caacattact aatgagtggc tcctttaacc tctccaccct
tatcacaaca caagaacacc 780tctggttact cctgccatca tggcccttgg ccatgatgtg
gtttatctcc acactagcag 840agaccaaccg aacccccttc gaccttgccg aaggggagtc
cgaactagtc tcaggcttca 900acatcgaata cgccgcaggc cccttcgccc tattcttcat
ggccgaatac acaaacatta 960ttatgatgaa caccctcacc actacaatct tcctaggaac
aacatatgac gcactctccc 1020ctgaactcta cacaacatat tttgtcacca agaccctact
tctaacctcc ctgttcttat 1080ggattcgaac agcatacccc cgattccgct acgaccaact
catgcacctc ctatggaaaa 1140acttcctacc actcacccta gcattactta tgtggtatgt
ctccatgccc attacaatct 1200ccagcattcc ccctcaaacc taagagcact gggacgccca
ccgccccttt ccctccgctg 1260ccaggcgagc atgttgtggt aattctggaa cacaagaaga
gaaattgctg ggtttagaac 1320aagattataa acgaattcgg tgctcagtga tcacttgaca
gttttttttt tttttaaata 1380ttacccaaaa tgctccccaa ataagaaatg catcagctca
gtcagtgaat acaaaaaagg 1440aattattttt ccctttgagg gtcttttata catctctcct
ccaaccccac cctctattct 1500gtttcttcct cctcacatgg gggtacacat acacagcttc
ctcttttggt tccatcctta 1560ccaccacacc acacgcacac tccacatgcc cagcagagtg
gcacttggtg gccagaaagt 1620gtgagcctca tgatctgctg tctgtagttc tgtgagctca
ggtccctcaa aggcctcgga 1680gcaccccctt ccttgtgact gagccagggc ctgcattttt
ggttttcccc accccacaca 1740ttctcaacca tagtccttct aacaatacca atagctagga
cccggctgct gtgcactggg 1800actggggatt ccacatgttt gccttgggag tctcaagctg
gactgcca 1848832648DNAArtificial
SequenceOPA1-opt_ND1-3'UTR 83gtgctgcccg cctagaaagg gtgaagtggt tgtttccgtg
acggactgag tacgggtgcc 60tgtcaggctc ttgcggaagt ccatgcgcca ttgggagggc
ctcggccgcg gctctgtgcc 120cttgctgctg agggccactt cctgggtcat tcctggaccg
ggagccgggc tggggctcac 180acgggggctc ccgcgtggcc gtctcggcgc ctgcgtgacc
tccccgccgg cgggatgtgg 240cgactacgtc gggccgctgt ggcctgatgc ccatggccaa
cctgctgctg ctgatcgtgc 300ccatcctgat cgccatggcc ttcctgatgc tgaccgagcg
caagatcctg ggctacatgc 360agctgcgcaa gggccccaac gtggtgggcc cctacggcct
gctgcagccc ttcgccgacg 420ccatgaagct gttcaccaag gagcccctga agcccgccac
cagcaccatc accctgtaca 480tcaccgcccc caccctggcc ctgaccatcg ccctgctgct
gtggaccccc ctgcccatgc 540ccaaccccct ggtgaacctg aacctgggcc tgctgttcat
cctggccacc agcagcctgg 600ccgtgtacag catcctgtgg agcggctggg ccagcaacag
caactacgcc ctgatcggcg 660ccctgcgcgc cgtggcccag accatcagct acgaggtgac
cctggccatc atcctgctga 720gcaccctgct gatgagcggc agcttcaacc tgagcaccct
gatcaccacc caggagcacc 780tgtggctgct gctgcccagc tggcccctgg ccatgatgtg
gttcatcagc accctggccg 840agaccaaccg cacccccttc gacctggccg agggcgagag
cgagctggtg agcggcttca 900acatcgagta cgccgccggc cccttcgccc tgttcttcat
ggccgagtac accaacatca 960tcatgatgaa caccctgacc accaccatct tcctgggcac
cacctacgac gccctgagcc 1020ccgagctgta caccacctac ttcgtgacca agaccctgct
gctgaccagc ctgttcctgt 1080ggatccgcac cgcctacccc cgcttccgct acgaccagct
gatgcacctg ctgtggaaga 1140acttcctgcc cctgaccctg gccctgctga tgtggtacgt
gagcatgccc atcaccatca 1200gcagcatccc cccccagacc taagagcact gggacgccca
ccgccccttt ccctccgctg 1260ccaggcgagc atgttgtggt aattctggaa cacaagaaga
gaaattgctg ggtttagaac 1320aagattataa acgaattcgg tgctcagtga tcacttgaca
gttttttttt tttttaaata 1380ttacccaaaa tgctccccaa ataagaaatg catcagctca
gtcagtgaat acaaaaaagg 1440aattattttt ccctttgagg gtcttttata catctctcct
ccaaccccac cctctattct 1500gtttcttcct cctcacatgg gggtacacat acacagcttc
ctcttttggt tccatcctta 1560ccaccacacc acacgcacac tccacatgcc cagcagagtg
gcacttggtg gccagaaagt 1620gtgagcctca tgatctgctg tctgtagttc tgtgagctca
ggtccctcaa aggcctcgga 1680gcaccccctt ccttgtgact gagccagggc ctgcattttt
ggttttcccc accccacaca 1740ttctcaacca tagtccttct aacaatacca atagctagga
cccggctgct gtgcactggg 1800actggggatt ccacatgttt gccttgggag tctcaagctg
gactgccagc ccctgtcctc 1860ccttcacccc cattgcgtat gagcatttca gaactccaag
gagtcacagg catctttata 1920gttcacgtta acatatagac actgttggaa gcagttcctt
ctaaaagggt agccctggac 1980ttaataccag ccggatacct ctggccccca ccccattact
gtacctctgg agtcactact 2040gtgggtcgcc actcctctgc tacacagcac ggctttttca
aggctgtatt gagaagggaa 2100gttaggaaga agggtgtgct gggctaacca gcccacagag
ctcacattcc tgtcccttgg 2160gtgaaaaata catgtccatc ctgatatctc ctgaattcag
aaattagcct ccacatgtgc 2220aatggcttta agagccagaa gcagggttct gggaattttg
caagttacct gtggccaggt 2280gtggtctcgg ttaccaaata cggttacctg cagcttttta
gtcctttgtg ctcccacggg 2340tctacagagt cccatctgcc caaaggtctt gaagcttgac
aggatgtttt cgattactca 2400gtctcccagg gcactactgg tccgtaggat tcgattggtc
ggggtaggag agttaaacaa 2460catttaaaca gagttctctc aaaaatgtct aaagggattg
taggtagata acatccaatc 2520actgtttgca cttatctgaa atcttccctc ttggctgccc
ccaggtattt actgtggaga 2580acattgcata ggaatgtctg gaaaaagctt ctacaacttg
ttacagcctt cacatttgta 2640gaagcttt
2648841848DNAArtificial SequenceOPA1-opt_ND1-3'UTR*
84gtgctgcccg cctagaaagg gtgaagtggt tgtttccgtg acggactgag tacgggtgcc
60tgtcaggctc ttgcggaagt ccatgcgcca ttgggagggc ctcggccgcg gctctgtgcc
120cttgctgctg agggccactt cctgggtcat tcctggaccg ggagccgggc tggggctcac
180acgggggctc ccgcgtggcc gtctcggcgc ctgcgtgacc tccccgccgg cgggatgtgg
240cgactacgtc gggccgctgt ggcctgatgc ccatggccaa cctgctgctg ctgatcgtgc
300ccatcctgat cgccatggcc ttcctgatgc tgaccgagcg caagatcctg ggctacatgc
360agctgcgcaa gggccccaac gtggtgggcc cctacggcct gctgcagccc ttcgccgacg
420ccatgaagct gttcaccaag gagcccctga agcccgccac cagcaccatc accctgtaca
480tcaccgcccc caccctggcc ctgaccatcg ccctgctgct gtggaccccc ctgcccatgc
540ccaaccccct ggtgaacctg aacctgggcc tgctgttcat cctggccacc agcagcctgg
600ccgtgtacag catcctgtgg agcggctggg ccagcaacag caactacgcc ctgatcggcg
660ccctgcgcgc cgtggcccag accatcagct acgaggtgac cctggccatc atcctgctga
720gcaccctgct gatgagcggc agcttcaacc tgagcaccct gatcaccacc caggagcacc
780tgtggctgct gctgcccagc tggcccctgg ccatgatgtg gttcatcagc accctggccg
840agaccaaccg cacccccttc gacctggccg agggcgagag cgagctggtg agcggcttca
900acatcgagta cgccgccggc cccttcgccc tgttcttcat ggccgagtac accaacatca
960tcatgatgaa caccctgacc accaccatct tcctgggcac cacctacgac gccctgagcc
1020ccgagctgta caccacctac ttcgtgacca agaccctgct gctgaccagc ctgttcctgt
1080ggatccgcac cgcctacccc cgcttccgct acgaccagct gatgcacctg ctgtggaaga
1140acttcctgcc cctgaccctg gccctgctga tgtggtacgt gagcatgccc atcaccatca
1200gcagcatccc cccccagacc taagagcact gggacgccca ccgccccttt ccctccgctg
1260ccaggcgagc atgttgtggt aattctggaa cacaagaaga gaaattgctg ggtttagaac
1320aagattataa acgaattcgg tgctcagtga tcacttgaca gttttttttt tttttaaata
1380ttacccaaaa tgctccccaa ataagaaatg catcagctca gtcagtgaat acaaaaaagg
1440aattattttt ccctttgagg gtcttttata catctctcct ccaaccccac cctctattct
1500gtttcttcct cctcacatgg gggtacacat acacagcttc ctcttttggt tccatcctta
1560ccaccacacc acacgcacac tccacatgcc cagcagagtg gcacttggtg gccagaaagt
1620gtgagcctca tgatctgctg tctgtagttc tgtgagctca ggtccctcaa aggcctcgga
1680gcaccccctt ccttgtgact gagccagggc ctgcattttt ggttttcccc accccacaca
1740ttctcaacca tagtccttct aacaatacca atagctagga cccggctgct gtgcactggg
1800actggggatt ccacatgttt gccttgggag tctcaagctg gactgcca
18488518DNAArtificial Sequencebeta-actin-S primer 85cgagatcgtg cgggacat
188619DNAArtificial
Sequencebeta-actin-A primer 86caggaaggag ggctggaac
198719DNAArtificial SequenceND4-S primer
87ctgcctacga caaacagac
198819DNAArtificial SequenceND4-A primer 88agtgcgttcg tagtttgag
198921DNAArtificial SequenceND6-F
primer 89atgatgtatg ctttgtttct g
219021DNAArtificial SequenceND6-R primer 90ctaattcccc cgagcaatct c
219118DNAArtificial
SequenceND6-S primer 91agtgtgggtt tagtaatg
189218DNAArtificial SequenceND6-A primer 92tgcctcagga
tactcctc
189320DNAArtificial Sequencebeta-actin-F primer 93ctccatcctg gcctcgctgt
209420DNAArtificial
Sequencebeta-actin-R primer 94gctgtcacct tcaccgttcc
209523DNAArtificial SequenceND6-F primer
95gggttttctt ctaagccttc tcc
239623DNAArtificial SequenceND6-R primer 96ccatcatact ctttcaccca cag
239720DNAArtificial
Sequenceopt_ND6-F primer 97cgcctgctga ccggctgcgt
209820DNAArtificial Sequenceopt_ND6-R 98ccaggcctcg
gggtactcct
209921DNAArtificial SequenceND1-F primer 99atggccgcat ctccgcacac t
2110021DNAArtificial SequenceND1-R
primer 100ttaggtttga gggggaatgc t
2110121DNAArtificial SequenceND1-F primer 101aacctcaacc taggcctcct
a 2110221DNAArtificial
SequenceND1-R primer 102tggcaggagt aaccagaggt g
2110323DNAArtificial SequenceND1-F primer
103aggaggctct gtctggtatc ttg
2310421DNAArtificial SequenceND1-R primer 104ttttaggggc tctttggtga a
2110522DNAArtificial
Sequenceopt-ND1-F primer 105gccgcctgct gaccggctgc gt
2210624DNAArtificial Sequenceopt-ND1-R primer
106tgatgtacag ggtgatggtg ctgg
2410719DNAArtificial SequenceND4-S primer 107gccaacagca actacgagc
1910820DNAArtificial
SequenceND4-A primer 108tgatgttgct ccagctgaag
2010920DNAArtificial Sequenceopt-ND4-S primer
109gcctgaccct gatcctgaac
2011020DNAArtificial Sequenceopt-ND4-A primer 110gtgcgctcgt agttgctgtt
20111376DNAHomo sapiens
111gggcagtgcc tccccgcccc gccgctggcg tcaagttcag ctccacgtgt gccatcagtg
60gatccgatcc gtccagccat ggcttcctat tccaagatgg tgtgaccaga catgcttcct
120gctccccgct tagcccacgg agtgactgtg gttgtggtgg gggggttctt aaaataactt
180tttagccccc gtcttcctat tttgagtttg gttcagatct taagcagctc catgcaactg
240tatttatttt tgatgacaag actcccatct aaagtttttc tcctgcctga tcatttcatt
300ggtggctgaa ggattctaga gaaccttttg ttcttgcaag gaaaacaaga atccaaaacc
360agtgactgtt ctgtga
376112146DNAHomo sapiens 112ggggtctttg tcctctgtac tgtctctctc cttgccccta
acccaaaaag cttcattttt 60ctgtgtaggc tgcacaagag ccttgattga agatatattc
tttctgaaca gtatttaagg 120tttccaataa aatgtacacc cctcag
1461131956DNAHomo sapiens 113tgttgggtcc aagaaggaat
ttctttccat ccctgtgagg caatgggtgg gaatgatagg 60acaggcaaag agaagcttcc
tcaggctagc aaaaatatca tttgatgtat tgattaaaaa 120agcacttgct tgatgtatct
ttggcgtgtg tgctactctc atctgtgtgt atgtgtgttg 180tgtgtgtgtg tgtgtgcatg
cacatatgtg ttcactctgc tactttgtaa gttttaggct 240aggttgcttt accagctgtt
tacttctttt ttgttgttgt tttgagacaa ggtttcgctc 300tgccaccctg gctggagtgc
agtggcgtga tcttggctca cggcaacctc tgcctcctgg 360ggctcaagca attatcccac
ctcagcctcc tgagcagctg ggactacagg tgcatgccac 420aacacctggc tgatatttgt
attttttgta gagacaggat tttgccaagt tgcccaggct 480ggtcttgaac tcctaggctt
aagcaatcca cccaccttgg cctcctgaag tgccaggatc 540acagacgtga gccactacac
ccagcccagc tgtttacttc tttaaccata cttttgattt 600tattttttga ccaaaatgaa
ctaacccagg taatcttcca gggaccgcaa ttccagaacc 660tcatagtatt tcttccattt
ccagcagctg attagaagtc caggatcatg tgaagtcagg 720cagggtcaca gttcctgatg
gcacattatg gacagagaat tccattttgt tttctaaccc 780atgatgaaaa cccacgtgag
tcagtgtgtg aacagggatc attaattttt tccccctagg 840tggaaggaaa aaggcactta
ctttgcaggt tacagaaatt actgggagag gatatcgtca 900taaaaagagc caggccaaat
tggaatattt ttgtgatctg catcatgatg ctgaaaatag 960caattatttg ggaattgggt
ttgaaaactg aattgttgcc agagaattaa accaggtgaa 1020aggtcctttt gaattcagat
tgtcttctga acatccaggc tgatcatctg agagcagtca 1080aatctacttc cccaaaaaga
gaccagggta ggtttatttg cttttatttt taatgtttgc 1140ctgtgtttcc aagtgtgaac
aaaacagtgt gtgatctatt cttggattca ttttgatcag 1200tatttattca aacccagtct
ctctccagga cataaaactg aaatcagata tgttcttttt 1260aagcccaaac cctctccttt
ctagatccaa cccttcaccc ctaattttat gatggctata 1320gccatggact tccccaagaa
aagatcaccc agaaataaga ccacctgtga cagttaccag 1380cttttattca taaccttagc
ttcccaacta ttgagcattt tctaaggtcc ctgctgtctt 1440ttggtctctg gtttgatttg
tggcaaacag atgaagtaac agactgctat gaaggaccac 1500aaaaacggca gcctctggaa
aaaccattag aaagtcagtg gcagatccag taaataatat 1560cgccagcctc agcataatct
gctgctgact cgattcagtg gactctaaag tgcccagcct 1620cctgacctga gctctcctgc
catctgtgag actaccagag gtcttatctg ctgtccacat 1680ggcaactggg catgagtacc
tggccacctt gcttccctct ttgcctggtc caagtgagtg 1740tctgctgcct ctgtcctgcc
ttgttttcct ggctctaaac caactccacc cactcttaat 1800ggaaactcag tctggctttg
tgtgtttctg ggaagcacat gacttctggg aatgggcaag 1860gaagaggagt gaaacaaaaa
ctgtcagcta tgtgtgcctg gtctgggatc cttctctggg 1920tgacagtggc atcatgaatc
ttagaatcag ctcccc 1956114411DNAHomo sapiens
114gaatcatgca agcttcctcc ctcagccatt gatggaaagt tcagcaagat cagcaacaaa
60accaagaaaa atgatccttg cgtgctgaat atctgaaaag agaaattttt cctacaaaat
120ctcttgggtc aagaaagttc tagaatttga attgataaac atggtgggtt ggctgagggt
180aagagtatat gaggaacctt ttaaacgaca acaatactgc tagctttcag gatgattttt
240aaaaaataga ttcaaatgtg ttatcctctc tctgaaacgc ttcctataac tcgagtttat
300aggggaagaa aaagctattg tttacaatta tatcaccatt aaggcaactg ctacaccctg
360ctttgtattc tgggctaaga ttcattaaaa actagctgct cttaacttac a
4111151465DNAHomo sapiens 115gagcactggg acgcccaccg cccctttccc tccgctgcca
ggcgagcatg ttgtggtaat 60tctggaacac aagaagagaa attgctgggt ttagaacaag
attataaacg aattcggtgc 120tcagtgatca cttgacagtt tttttttttt ttaaatatta
cccaaaatgc tccccaaata 180agaaatgcat cagctcagtc agtgaataca aaaaaggaat
tatttttccc tttgagggtc 240tttatacatc tctcctccaa ccccaccctc tattctgttt
cttcctcctc acatgggggt 300acacatacac agcttcctct tttggttcca tccttaccac
cacaccacac gcacactcca 360catgcccagc agagtggcac ttggtggcca gaaagtgtga
gcctcatgat ctgctgtctg 420tagttctgtg agctcaggtc cctcaaaggc ctcggagcac
ccccttcctg gtgactgagc 480cagggcctgc atttttggtt ttccccaccc cacacattct
caaccatagt ccttctaaca 540ataccaatag ctaggacccg gctgctgtgc actgggactg
gggattccac atgtttgcct 600tgggagtctc aagctggact gccagcccct gtcctccctt
cacccccatt gcgtatgagc 660atttcagaac tccaaggagt cacaggcatc tttatagttc
acgttaacat atagacactg 720ttggaagcag ttccttctaa aagggtagcc ctggacttaa
taccagccgg atacctctgg 780cccccacccc attactgtac ctctggagtc actactgtgg
gtcgccactc ctctgctaca 840cagcacggct ttttcaaggc tgtattgaga agggaagtta
ggaagaaggg tgtgctgggc 900taaccagccc acagagctca cattcctgtc ccttgggtga
aaaatacatg tccatcctga 960tatctcctga attcagaaat tagcctccac atgtgcaatg
gctttaagag ccagaagcag 1020ggttctggga attttgcaag ttatcctgtg gccaggtgtg
gtctcggtta ccaaatacgg 1080ttacctgcag ctttttagtc ctttgtgctc ccacgggtct
gcagagtccc atctgcccaa 1140aggtcttgaa gcttgacagg atgttttcat tactcagtct
cccagggcac tgctggtccg 1200tagggattca ttggtcgggg tgggagagtt aaacaacatt
taaacagagt tctctcaaaa 1260atgtctaaag ggattgtagg tagataacat ccaatcactg
tttgcactta tctgaaatct 1320tccctcttgg ctgcccccag gtatttactg tggagaacat
tgcataggaa tgtctggaaa 1380aagcctctac aacttgttac agccttcaca tttgtacaat
tcattgattc tcttttcctt 1440ccacaataaa atggtataca agaac
1465116288DNAHomo sapiens 116gagacttgga ctcaagtcat
aggcttcttt cagtctttat gtcacctcag gagacttatt 60tgagaggaag ccttctgtac
ttgaagttga tttgaaatat gtaagaattg atgatgtatt 120tgcaaacatt aatgtgaaat
aaattgaatt taatgttgaa tactttcagg cattcactta 180ataaagacac tgttaagcac
tgttatgctc agtcatacac gcgaaaggta caatgtcttt 240tagctaattc taattaaaaa
ttacagactg gtgtacaaga tacttgtg 28811783DNAHomo sapiens
117cccaccaccc tggcctgctg tcctgcgtct atccatgtgg aatgctggac aataaagcga
60gtgctgccca ccctccagct gcc
8311866DNAHomo sapiens 118tttatattga actgtaaata tgtcactaga gaaataaaat
atggacttcc aatctacgta 60aactta
66119214DNAHomo sapiens 119accacgatcg ttatgctgag
tatgttaagc tctttatgac tgtttttgta gtggtataga 60gtactgcaga atacagtaag
ctgctctatt gtagcatttc ttgatgttgc ttagtcactt 120atttcataaa caacttaatg
ttctgaataa tttcttacta aacattttgt tattgggcaa 180gtgattgaaa atagtaaatg
ctttgtgtga ttga 214120286DNAHomo sapiens
120tcttggaata taaagaattt cttcaggttg aattacctag aagtttgtca ctgacttgtg
60ttcctgaact atgacacatg aatatgtggg ctaagaaata gttcctcttg ataaataaac
120aattaacaaa tactttggac agtaagtctt tctcagttct taatgataat gcagggcact
180tactagcata agaattggtt tgggatttaa ctgtttatga agctaacttg atttccgtgt
240tttgttaaaa tttcattgtt ctagcacatc tttaactgtg atagtt
286121721DNAHomo sapiens 121gagacgtgca cttggtcgtg cgcccaggga ggaagccgca
ccaccagcca gcgcaggccc 60tggtggagag gcctccctgg ctgcctctgg gaggggtgct
gccttgtaga tggagcaagt 120gagcactgag ggtctggtgc caatcctgta ggcacaaaac
cagaagtttc tacattctct 180atttttgtta atcatcttct ctttttccag aatttggaag
ctagaatggt gggaatgtca 240gtagtgccag aaagagagaa ccaagcttgt ctttaaagtt
actgatcaca ggacgttgct 300ttttcactgt ttcctattaa tcttcagctg aacacaagca
aaccttctca ggaggtgtct 360cctaccctct tattgttcct cttacgctct gctcaatgaa
accttcctct tgagggtcat 420tttcctttct gtattaatta taccagtgtt aagtgacata
gataagaact ttgcacactt 480caaatcagag cagtgattct ctcttctctc cccttttcct
tcagagtgaa tcatccagac 540tcctcatgga taggtcgggt gttaaagttg ttttgattat
gtaccttttg atagatccac 600ataaaaagaa atgtgaagtt ttcttttact atcttttcat
ttatcaagca gagacctttg 660ttgggaggcg gtttgggaga acacatttct aatttgaatg
aaatgaaatc tattttcagt 720g
721122163DNAHomo sapiens 122cagaagaagt gacggctggg
ggcacagtgg gctgggcgcc cctgcagaac atgaaccttc 60cgctcctggc tgccacaggg
tcctccgatg ctggcctttg cgcctctaga ggcagccact 120catggattca agtcctggct
ccgcctcttc catcaggacc act 16312360DNAHomo sapiens
123agaggacaca ctctgcaccc ccccacccca cgaccttggc ccgagcccct ccgtgaggaa
6012465DNAHomo sapiens 124agcccttccg ccaggctgtg tgtcaggccc gtggtgggtg
ttttgtagta gtgtagagca 60ttgca
65125231DNAHomo sapiens 125cttatgttct gtgcgcattc
tggcaggaat tctgtctctt cagagactca tcctcaaaac 60aagacttgac actgtgtcct
tgccccagtc ctaggaactg tggcacacag agatgttcat 120tttaaaaacg gatttcatga
aacactcttg tacttatgtt tataagagag cactgggtag 180ccaagtgatc ttcccattca
cagagttagt aaacctctgt actacatgct g 23112628PRTHomo sapiens
126Met Ala Ala Ser Pro His Thr Leu Ser Ser Arg Leu Leu Thr Gly Cys1
5 10 15Val Gly Gly Ser Val Trp
Tyr Leu Glu Arg Arg Thr 20 2512729PRTHomo
sapiens 127Met Ser Val Leu Thr Arg Leu Leu Leu Arg Gly Leu Thr Arg Leu
Gly1 5 10 15Ser Ala Ala
Pro Val Arg Arg Ala Arg Ile His Ser Leu 20
2512810PRTHomo sapiens 128Met Trp Arg Leu Arg Arg Ala Ala Val Ala1
5 1012928PRTHomo sapiens 129Met Ala Ala Ser Pro
His Thr Leu Ser Ser Arg Leu Leu Thr Gly Cys1 5
10 15Val Gly Gly Ser Val Trp Tyr Leu Glu Arg Arg
Thr 20 25130122PRTSaccharomyces cerevisiae
130Met Ala Phe Lys Ser Phe Ile Tyr Ser Lys Gly Tyr His Arg Ser Ala1
5 10 15Ala Gln Lys Lys Thr Ala
Thr Ser Phe Phe Asp Ser Ser Tyr Gln Tyr 20 25
30Leu Arg Gln Asn Gln Gly Leu Val Asn Ser Asp Pro Val
Leu His Ala 35 40 45Ser His Leu
His Pro His Pro Val Val Val Ala Asn Val Asn Tyr Asn 50
55 60Asn Val Asp Asp Ile Leu His Pro His Asp Leu Asp
Ser Ser Ile Asn65 70 75
80Asn Thr Asn Asn Pro Leu Thr His Glu Glu Leu Leu Tyr Asn Gln Asn
85 90 95Val Ser Leu Arg Ser Leu
Lys Gln Gln Gln Ser Thr Asn Tyr Val Asn 100
105 110Asn Asn Asn Asn Asn Gln His Arg Tyr Tyr 115
120131174PRTLarimichthys crocea 131Met Arg Lys Arg Ser
Leu Arg Cys His Leu Trp Ser Ala Asn Ala Ser1 5
10 15Leu Ser Pro Arg Lys Asp Glu Val Thr Ser Arg
Lys Glu Ser Glu Asn 20 25
30Leu Val Lys Gly Lys Lys Asn Lys Lys Ser His Leu His Leu Leu Leu
35 40 45Phe Thr Ala Ser Lys Ile Gly Thr
Asp Ser Val Phe Asp Val Gln Lys 50 55
60Ser Lys Glu Cys Cys Lys Glu Leu Gly Leu Leu Phe Thr Ser Leu Ile65
70 75 80His Ser Ile Gly Ser
Phe Pro Phe Asp Glu Glu Pro Lys Ala Ala Ala 85
90 95Val Phe Leu Pro Gly Ser Leu Pro Gln Leu Thr
Val Leu Val Leu Ala 100 105
110Pro Gly Ser Gly Ser Cys Pro Thr Gly Lys Ser Thr Pro His Leu Ala
115 120 125Ala Ser Gly Arg Asn Ala Glu
Leu Leu Arg Pro Gln Asn Ser Met Ile 130 135
140Val Arg Gln Phe Thr Cys Arg Gly Thr Ile Ser Ser His Leu Cys
Ala145 150 155 160His Leu
Arg Lys Pro His Asp Ser Arg Asn Met Ala Arg Pro 165
17013256PRTTrypanosoma brucei 132Met Leu Arg Arg Thr Ser Phe Asn
Phe Thr Gly Arg Ala Met Ile Ser1 5 10
15Arg Gly Ser Pro Glu Trp Ser His Arg Leu Asp Leu Lys Lys
Gly Lys 20 25 30Lys Thr Thr
Met Met His Lys Leu Gly Thr Ser Lys Pro Asn Asn Ala 35
40 45Leu Gln Tyr Ala Gln Met Thr Leu 50
5513346PRTNeurospora crassa 133Met Ile Ser Arg Ser Ala Leu Ser
Arg Gly Ser Gln Leu Ala Leu Arg1 5 10
15Arg Pro Ala Ala Ala Lys Thr Ala Gln Arg Gly Phe Ala Ala
Ala Ala 20 25 30Ala Ser Pro
Ala Ala Ser Tyr Glu Pro Thr Thr Ile Ala Gly 35 40
45134128PRTHomo sapiens 134Met Pro Glu Leu Ile Leu Tyr
Val Ala Ile Thr Leu Ser Val Ala Glu1 5 10
15Arg Leu Val Gly Pro Gly His Ala Cys Ala Glu Pro Ser
Phe Arg Ser 20 25 30Ser Arg
Cys Ser Ala Pro Leu Cys Leu Leu Cys Ser Gly Ser Ser Ser 35
40 45Pro Ala Thr Ala Pro His Pro Leu Lys Met
Phe Ala Cys Ser Lys Phe 50 55 60Val
Ser Thr Pro Ser Leu Val Lys Ser Thr Ser Gln Leu Leu Ser Arg65
70 75 80Pro Leu Ser Ala Val Val
Leu Lys Arg Pro Glu Ile Leu Thr Asp Glu 85
90 95Ser Leu Ser Ser Leu Ala Val Ser Cys Pro Leu Thr
Ser Leu Val Ser 100 105 110Ser
Arg Ser Phe Gln Thr Ser Ala Ile Ser Arg Asp Ile Asp Thr Ala 115
120 125135115PRTHomo sapiens 135Met Tyr Arg
Leu Met Ser Ala Val Thr Ala Arg Ala Ala Ala Pro Gly1 5
10 15Gly Leu Ala Ser Ser Cys Gly Arg Arg
Gly Val His Gln Arg Ala Gly 20 25
30Leu Pro Pro Leu Gly His Gly Trp Val Gly Gly Leu Gly Leu Gly Leu
35 40 45Gly Leu Ala Leu Gly Val Lys
Leu Ala Gly Gly Leu Arg Gly Ala Ala 50 55
60Pro Ala Gln Ser Pro Ala Ala Pro Asp Pro Glu Ala Ser Pro Leu Ala65
70 75 80Glu Pro Pro Gln
Glu Gln Ser Leu Ala Pro Trp Ser Pro Gln Thr Pro 85
90 95Ala Pro Pro Cys Ser Arg Cys Phe Ala Arg
Ala Ile Glu Ser Ser Arg 100 105
110Asp Leu Leu 115136140PRTSchizosaccharomyces pombe 136Met Thr
Val Leu Ala Pro Leu Arg Arg Leu His Thr Arg Ala Ala Phe1 5
10 15Ser Ser Tyr Gly Arg Glu Ile Ala
Leu Gln Lys Arg Phe Leu Asn Leu 20 25
30Asn Ser Cys Ser Ala Val Arg Arg Tyr Gly Thr Gly Phe Ser Asn
Asn 35 40 45Leu Arg Ile Lys Lys
Leu Lys Asn Ala Phe Gly Val Val Arg Ala Asn 50 55
60Ser Thr Lys Ser Thr Ser Thr Val Thr Thr Ala Ser Pro Ile
Lys Tyr65 70 75 80Asp
Ser Ser Phe Val Gly Lys Thr Gly Gly Glu Ile Phe His Asp Met
85 90 95Met Leu Lys His Asn Val Lys
His Val Phe Gly Tyr Pro Gly Gly Ala 100 105
110Ile Leu Pro Val Phe Asp Ala Ile Tyr Arg Ser Pro His Phe
Glu Phe 115 120 125Ile Leu Pro Arg
His Glu Gln Ala Ala Gly His Ala 130 135
140137125PRTGlycine max 137Met Ile Leu Cys Pro Leu Glu Ala Phe Ile Val
Gln His Ile Leu Thr1 5 10
15Ile Ser Val Met Gly Leu Leu Ser Cys Phe Arg Ser Thr Val Leu Arg
20 25 30Lys Cys Ser Lys Gly Ser Ser
Gly Met Ser Arg Phe Leu Tyr Thr Asn 35 40
45Asn Phe Gln Arg Asn Leu Ile Ser Ser Gly Gly Asn Glu Ser Tyr
Tyr 50 55 60Gly Tyr Phe Asn Arg Arg
Ser Tyr Thr Ser Leu Tyr Met Gly Thr Gly65 70
75 80Thr Val Gly Gly Ile Thr Ser Ala Arg Ile Arg
Val Pro Asn Val Gly 85 90
95Cys Glu Gly Phe Met Cys Ser Ser His Leu Ser Ile Thr Gln Arg Asn
100 105 110Ser Arg Leu Ile His Ser
Thr Ser Lys Ile Val Pro Asn 115 120
125138107PRTChlamydomonas reinhardtii 138Met Ala Leu Gln Gln Ala Ala Pro
Arg Val Phe Gly Leu Leu Gly Arg1 5 10
15Ala Pro Val Ala Leu Gly Gln Ser Gly Ile Leu Thr Gly Ser
Ser Gly 20 25 30Phe Lys Asn
Gln Gly Phe Asn Gly Ser Leu Gln Ser Val Glu Asn His 35
40 45Val Tyr Ala Gln Ala Phe Ser Thr Ser Ser Gln
Glu Glu Gln Ala Ala 50 55 60Pro Ser
Ile Gln Gly Ala Ser Gly Met Lys Leu Pro Gly Met Ala Gly65
70 75 80Ser Met Leu Leu Gly Lys Ser
Arg Ser Gly Leu Arg Thr Gly Ser Met 85 90
95Val Pro Phe Ala Ala Gln Gln Ala Met Asn Met
100 10513987PRTHomo sapiens 139Met Trp Arg Leu Arg Arg
Ala Ala Val Ala Cys Glu Val Cys Gln Ser1 5
10 15Leu Val Lys His Ser Ser Gly Ile Lys Gly Ser Leu
Pro Leu Gln Lys 20 25 30Leu
His Leu Val Ser Arg Ser Ile Tyr His Ser His His Pro Thr Leu 35
40 45Lys Leu Gln Arg Pro Gln Leu Arg Thr
Ser Phe Gln Gln Phe Ser Ser 50 55
60Leu Thr Asn Leu Pro Leu Arg Lys Leu Lys Phe Ser Pro Ile Lys Tyr65
70 75 80Gly Tyr Gln Pro Arg
Arg Asn 8514056PRTHomo sapiens 140Met Ala Val Leu Trp Arg
Leu Ser Ala Val Cys Gly Ala Leu Gly Gly1 5
10 15Arg Ala Leu Leu Leu Arg Thr Pro Val Val Arg Pro
Ala His Ile Ser 20 25 30Ala
Phe Leu Gln Asp Arg Pro Ile Pro Glu Trp Cys Gly Val Gln His 35
40 45Ile His Leu Ser Pro Ser His His 50
55141162PRTHomo sapiens 141Met Ala Ala Ile Leu Gly Asp
Thr Ile Met Val Ala Lys Gly Leu Val1 5 10
15Lys Leu Thr Gln Ala Ala Val Glu Thr His Leu Gln His
Leu Gly Ile 20 25 30Gly Gly
Glu Leu Ile Met Ala Ala Arg Ala Leu Gln Ser Thr Ala Val 35
40 45Glu Gln Ile Gly Met Phe Leu Gly Lys Val
Gln Gly Gln Asp Lys His 50 55 60Glu
Glu Tyr Phe Ala Glu Asn Phe Gly Gly Pro Glu Gly Glu Phe His65
70 75 80Phe Ser Val Pro His Ala
Ala Gly Ala Ser Thr Asp Phe Ser Ser Ala 85
90 95Ser Ala Pro Asp Gln Ser Ala Pro Pro Ser Leu Gly
His Ala His Ser 100 105 110Glu
Gly Pro Ala Pro Ala Tyr Val Ala Ser Gly Pro Phe Arg Glu Ala 115
120 125Gly Phe Pro Gly Gln Ala Ser Ser Pro
Leu Gly Arg Ala Asn Gly Arg 130 135
140Leu Phe Ala Asn Pro Arg Asp Ser Phe Ser Ala Met Gly Phe Gln Arg145
150 155 160Arg
Phe142117PRTOryza sativa 142Met Ala Leu Leu Leu Arg His Ser Pro Lys Leu
Arg Arg Ala His Ala1 5 10
15Ile Leu Gly Cys Glu Arg Gly Thr Val Val Arg His Phe Ser Ser Ser
20 25 30Thr Cys Ser Ser Leu Val Lys
Glu Asp Thr Val Ser Ser Ser Asn Leu 35 40
45His Pro Glu Tyr Ala Lys Lys Ile Gly Gly Ser Asp Phe Ser His
Asp 50 55 60Arg Gln Ser Gly Lys Glu
Leu Gln Asn Phe Lys Val Ser Pro Gln Glu65 70
75 80Ala Ser Arg Ala Ser Asn Phe Met Arg Ala Ser
Lys Tyr Gly Met Pro 85 90
95Ile Thr Ala Asn Gly Val His Ser Leu Phe Ser Cys Gly Gln Val Val
100 105 110Pro Ser Arg Cys Phe
11514366PRTNeurospora crassa 143Met Ala Ser Thr Arg Val Leu Ala Ser Arg
Leu Ala Ser Gln Met Ala1 5 10
15Ala Ser Ala Lys Val Ala Arg Pro Ala Val Arg Val Ala Gln Val Ser
20 25 30Lys Arg Thr Ile Gln Thr
Gly Ser Pro Leu Gln Thr Leu Lys Arg Thr 35 40
45Gln Met Thr Ser Ile Val Asn Ala Thr Thr Arg Gln Ala Phe
Gln Lys 50 55 60Arg
Ala6514444PRTHomo sapiens 144Met Leu Ala Ala Arg Leu Val Cys Leu Arg Thr
Leu Pro Ser Arg Val1 5 10
15Phe His Pro Ala Phe Thr Lys Ala Ser Pro Val Val Lys Asn Ser Ile
20 25 30Thr Lys Asn Gln Trp Leu Leu
Thr Pro Ser Arg Glu 35 4014568PRTHomo sapiens
145Met Ala Ser Arg Val Leu Ser Ala Tyr Val Ser Arg Leu Pro Ala Ala1
5 10 15Phe Ala Pro Leu Pro Arg
Val Arg Met Leu Ala Val Ala Arg Pro Leu 20 25
30Ser Thr Ala Leu Cys Ser Ala Gly Thr Gln Thr Arg Leu
Gly Thr Leu 35 40 45Gln Pro Ala
Leu Val Leu Ala Gln Val Pro Gly Arg Val Thr Gln Leu 50
55 60Cys Arg Gln Tyr6514667PRTHomo sapiens 146Met Phe
Ala Cys Ala Lys Leu Ala Cys Thr Pro Ser Leu Ile Arg Ala1 5
10 15Gly Ser Arg Val Ala Tyr Arg Pro
Ile Ser Ala Ser Val Leu Ser Arg 20 25
30Pro Glu Ala Ser Arg Thr Gly Glu Gly Ser Thr Val Phe Asn Gly
Ala 35 40 45Gln Asn Gly Val Ser
Gln Leu Ile Gln Arg Glu Phe Gln Thr Ser Ala 50 55
60Ile Ser Arg65147273PRTArtificial SequencecrATP6_hsADCK3
147Met Ala Leu Gln Gln Ala Ala Pro Arg Val Phe Gly Leu Leu Gly Arg1
5 10 15Ala Pro Val Ala Leu Gly
Gln Ser Gly Ile Leu Thr Gly Ser Ser Gly 20 25
30Phe Lys Asn Gln Gly Phe Asn Gly Ser Leu Gln Ser Val
Glu Asn His 35 40 45Val Tyr Ala
Gln Ala Phe Ser Thr Ser Ser Gln Glu Glu Gln Ala Ala 50
55 60Pro Ser Ile Gln Gly Ala Ser Gly Met Lys Leu Pro
Gly Met Ala Gly65 70 75
80Ser Met Leu Leu Gly Lys Ser Arg Ser Gly Leu Arg Thr Gly Ser Met
85 90 95Val Pro Phe Ala Ala Gln
Gln Ala Met Asn Met Gly Gly Met Ala Ala 100
105 110Ile Leu Gly Asp Thr Ile Met Val Ala Lys Gly Leu
Val Lys Leu Thr 115 120 125Gln Ala
Ala Val Glu Thr His Leu Gln His Leu Gly Ile Gly Gly Glu 130
135 140Leu Ile Met Ala Ala Arg Ala Leu Gln Ser Thr
Ala Val Glu Gln Ile145 150 155
160Gly Met Phe Leu Gly Lys Val Gln Gly Gln Asp Lys His Glu Glu Tyr
165 170 175Phe Ala Glu Asn
Phe Gly Gly Pro Glu Gly Glu Phe His Phe Ser Val 180
185 190Pro His Ala Ala Gly Ala Ser Thr Asp Phe Ser
Ser Ala Ser Ala Pro 195 200 205Asp
Gln Ser Ala Pro Pro Ser Leu Gly His Ala His Ser Glu Gly Pro 210
215 220Ala Pro Ala Tyr Val Ala Ser Gly Pro Phe
Arg Glu Ala Gly Phe Pro225 230 235
240Gly Gln Ala Ser Ser Pro Leu Gly Arg Ala Asn Gly Arg Leu Phe
Ala 245 250 255Asn Pro Arg
Asp Ser Phe Ser Ala Met Gly Phe Gln Arg Arg Phe Gly 260
265 270Gly148132PRTArtificial
SequencencATP9_ncATP9 148Met Ala Ser Thr Arg Val Leu Ala Ser Arg Leu Ala
Ser Gln Met Ala1 5 10
15Ala Ser Ala Lys Val Ala Arg Pro Ala Val Arg Val Ala Gln Val Ser
20 25 30Lys Arg Thr Ile Gln Thr Gly
Ser Pro Leu Gln Thr Leu Lys Arg Thr 35 40
45Gln Met Thr Ser Ile Val Asn Ala Thr Thr Arg Gln Ala Phe Gln
Lys 50 55 60Arg Ala Met Ala Ser Thr
Arg Val Leu Ala Ser Arg Leu Ala Ser Gln65 70
75 80Met Ala Ala Ser Ala Lys Val Ala Arg Pro Ala
Val Arg Val Ala Gln 85 90
95Val Ser Lys Arg Thr Ile Gln Thr Gly Ser Pro Leu Gln Thr Leu Lys
100 105 110Arg Thr Gln Met Thr Ser
Ile Val Asn Ala Thr Thr Arg Gln Ala Phe 115 120
125Gln Lys Arg Ala 130149119PRTZea mays 149Met Ala Leu
Leu Arg Ala Ala Val Ser Glu Leu Arg Arg Arg Gly Arg1 5
10 15Gly Ala Leu Thr Pro Leu Pro Ala Leu
Ser Ser Leu Leu Ser Ser Leu 20 25
30Ser Pro Arg Ser Pro Ala Ser Thr Arg Pro Glu Pro Asn Asn Pro His
35 40 45Ala Asp Arg Arg His Val Ile
Ala Leu Arg Arg Cys Pro Pro Leu Pro 50 55
60Ala Ser Ala Val Leu Ala Pro Glu Leu Leu His Ala Arg Gly Leu Leu65
70 75 80Pro Arg His Trp
Ser His Ala Ser Pro Leu Ser Thr Ser Ser Ser Ser 85
90 95Ser Arg Pro Ala Asp Lys Ala Gln Leu Thr
Trp Val Asp Lys Trp Ile 100 105
110Pro Glu Ala Ala Arg Pro Tyr 115150391PRTArtificial
SequencencATP9_zmLOC100282174_spilv1_ncATP9 150Met Ala Ser Thr Arg Val
Leu Ala Ser Arg Leu Ala Ser Gln Met Ala1 5
10 15Ala Ser Ala Lys Val Ala Arg Pro Ala Val Arg Val
Ala Gln Val Ser 20 25 30Lys
Arg Thr Ile Gln Thr Gly Ser Pro Leu Gln Thr Leu Lys Arg Thr 35
40 45Gln Met Thr Ser Ile Val Asn Ala Thr
Thr Arg Gln Ala Phe Gln Lys 50 55
60Arg Ala Met Ala Leu Leu Arg Ala Ala Val Ser Glu Leu Arg Arg Arg65
70 75 80Gly Arg Gly Ala Leu
Thr Pro Leu Pro Ala Leu Ser Ser Leu Leu Ser 85
90 95Ser Leu Ser Pro Arg Ser Pro Ala Ser Thr Arg
Pro Glu Pro Asn Asn 100 105
110Pro His Ala Asp Arg Arg His Val Ile Ala Leu Arg Arg Cys Pro Pro
115 120 125Leu Pro Ala Ser Ala Val Leu
Ala Pro Glu Leu Leu His Ala Arg Gly 130 135
140Leu Leu Pro Arg His Trp Ser His Ala Ser Pro Leu Ser Thr Ser
Ser145 150 155 160Ser Ser
Ser Arg Pro Ala Asp Lys Ala Gln Leu Thr Trp Val Asp Lys
165 170 175Trp Ile Pro Glu Ala Ala Arg
Pro Tyr Met Thr Val Leu Ala Pro Leu 180 185
190Arg Arg Leu His Thr Arg Ala Ala Phe Ser Ser Tyr Gly Arg
Glu Ile 195 200 205Ala Leu Gln Lys
Arg Phe Leu Asn Leu Asn Ser Cys Ser Ala Val Arg 210
215 220Arg Tyr Gly Thr Gly Phe Ser Asn Asn Leu Arg Ile
Lys Lys Leu Lys225 230 235
240Asn Ala Phe Gly Val Val Arg Ala Asn Ser Thr Lys Ser Thr Ser Thr
245 250 255Val Thr Thr Ala Ser
Pro Ile Lys Tyr Asp Ser Ser Phe Val Gly Lys 260
265 270Thr Gly Gly Glu Ile Phe His Asp Met Met Leu Lys
His Asn Val Lys 275 280 285His Val
Phe Gly Tyr Pro Gly Gly Ala Ile Leu Pro Val Phe Asp Ala 290
295 300Ile Tyr Arg Ser Pro His Phe Glu Phe Ile Leu
Pro Arg His Glu Gln305 310 315
320Ala Ala Gly His Ala Met Ala Ser Thr Arg Val Leu Ala Ser Arg Leu
325 330 335Ala Ser Gln Met
Ala Ala Ser Ala Lys Val Ala Arg Pro Ala Val Arg 340
345 350Val Ala Gln Val Ser Lys Arg Thr Ile Gln Thr
Gly Ser Pro Leu Gln 355 360 365Thr
Leu Lys Arg Thr Gln Met Thr Ser Ile Val Asn Ala Thr Thr Arg 370
375 380Gln Ala Phe Gln Lys Arg Ala385
390151455PRTArtificial SequencezmLOC100282174_hsADCK3_crATP6
_hsATP5G3 151Met Ala Leu Leu Arg Ala Ala Val Ser Glu Leu Arg Arg Arg Gly
Arg1 5 10 15Gly Ala Leu
Thr Pro Leu Pro Ala Leu Ser Ser Leu Leu Ser Ser Leu 20
25 30Ser Pro Arg Ser Pro Ala Ser Thr Arg Pro
Glu Pro Asn Asn Pro His 35 40
45Ala Asp Arg Arg His Val Ile Ala Leu Arg Arg Cys Pro Pro Leu Pro 50
55 60Ala Ser Ala Val Leu Ala Pro Glu Leu
Leu His Ala Arg Gly Leu Leu65 70 75
80Pro Arg His Trp Ser His Ala Ser Pro Leu Ser Thr Ser Ser
Ser Ser 85 90 95Ser Arg
Pro Ala Asp Lys Ala Gln Leu Thr Trp Val Asp Lys Trp Ile 100
105 110Pro Glu Ala Ala Arg Pro Tyr Met Ala
Ala Ile Leu Gly Asp Thr Ile 115 120
125Met Val Ala Lys Gly Leu Val Lys Leu Thr Gln Ala Ala Val Glu Thr
130 135 140His Leu Gln His Leu Gly Ile
Gly Gly Glu Leu Ile Met Ala Ala Arg145 150
155 160Ala Leu Gln Ser Thr Ala Val Glu Gln Ile Gly Met
Phe Leu Gly Lys 165 170
175Val Gln Gly Gln Asp Lys His Glu Glu Tyr Phe Ala Glu Asn Phe Gly
180 185 190Gly Pro Glu Gly Glu Phe
His Phe Ser Val Pro His Ala Ala Gly Ala 195 200
205Ser Thr Asp Phe Ser Ser Ala Ser Ala Pro Asp Gln Ser Ala
Pro Pro 210 215 220Ser Leu Gly His Ala
His Ser Glu Gly Pro Ala Pro Ala Tyr Val Ala225 230
235 240Ser Gly Pro Phe Arg Glu Ala Gly Phe Pro
Gly Gln Ala Ser Ser Pro 245 250
255Leu Gly Arg Ala Asn Gly Arg Leu Phe Ala Asn Pro Arg Asp Ser Phe
260 265 270Ser Ala Met Gly Phe
Gln Arg Arg Phe Met Ala Leu Gln Gln Ala Ala 275
280 285Pro Arg Val Phe Gly Leu Leu Gly Arg Ala Pro Val
Ala Leu Gly Gln 290 295 300Ser Gly Ile
Leu Thr Gly Ser Ser Gly Phe Lys Asn Gln Gly Phe Asn305
310 315 320Gly Ser Leu Gln Ser Val Glu
Asn His Val Tyr Ala Gln Ala Phe Ser 325
330 335Thr Ser Ser Gln Glu Glu Gln Ala Ala Pro Ser Ile
Gln Gly Ala Ser 340 345 350Gly
Met Lys Leu Pro Gly Met Ala Gly Ser Met Leu Leu Gly Lys Ser 355
360 365Arg Ser Gly Leu Arg Thr Gly Ser Met
Val Pro Phe Ala Ala Gln Gln 370 375
380Ala Met Asn Met Met Phe Ala Cys Ala Lys Leu Ala Cys Thr Pro Ser385
390 395 400Leu Ile Arg Ala
Gly Ser Arg Val Ala Tyr Arg Pro Ile Ser Ala Ser 405
410 415Val Leu Ser Arg Pro Glu Ala Ser Arg Thr
Gly Glu Gly Ser Thr Val 420 425
430Phe Asn Gly Ala Gln Asn Gly Val Ser Gln Leu Ile Gln Arg Glu Phe
435 440 445Gln Thr Ser Ala Ile Ser Arg
450 455152348PRTArtificial
SequencezmLOC100282174_hsADCK3_hsATP5G3 152Met Ala Leu Leu Arg Ala Ala
Val Ser Glu Leu Arg Arg Arg Gly Arg1 5 10
15Gly Ala Leu Thr Pro Leu Pro Ala Leu Ser Ser Leu Leu
Ser Ser Leu 20 25 30Ser Pro
Arg Ser Pro Ala Ser Thr Arg Pro Glu Pro Asn Asn Pro His 35
40 45Ala Asp Arg Arg His Val Ile Ala Leu Arg
Arg Cys Pro Pro Leu Pro 50 55 60Ala
Ser Ala Val Leu Ala Pro Glu Leu Leu His Ala Arg Gly Leu Leu65
70 75 80Pro Arg His Trp Ser His
Ala Ser Pro Leu Ser Thr Ser Ser Ser Ser 85
90 95Ser Arg Pro Ala Asp Lys Ala Gln Leu Thr Trp Val
Asp Lys Trp Ile 100 105 110Pro
Glu Ala Ala Arg Pro Tyr Met Ala Ala Ile Leu Gly Asp Thr Ile 115
120 125Met Val Ala Lys Gly Leu Val Lys Leu
Thr Gln Ala Ala Val Glu Thr 130 135
140His Leu Gln His Leu Gly Ile Gly Gly Glu Leu Ile Met Ala Ala Arg145
150 155 160Ala Leu Gln Ser
Thr Ala Val Glu Gln Ile Gly Met Phe Leu Gly Lys 165
170 175Val Gln Gly Gln Asp Lys His Glu Glu Tyr
Phe Ala Glu Asn Phe Gly 180 185
190Gly Pro Glu Gly Glu Phe His Phe Ser Val Pro His Ala Ala Gly Ala
195 200 205Ser Thr Asp Phe Ser Ser Ala
Ser Ala Pro Asp Gln Ser Ala Pro Pro 210 215
220Ser Leu Gly His Ala His Ser Glu Gly Pro Ala Pro Ala Tyr Val
Ala225 230 235 240Ser Gly
Pro Phe Arg Glu Ala Gly Phe Pro Gly Gln Ala Ser Ser Pro
245 250 255Leu Gly Arg Ala Asn Gly Arg
Leu Phe Ala Asn Pro Arg Asp Ser Phe 260 265
270Ser Ala Met Gly Phe Gln Arg Arg Phe Met Phe Ala Cys Ala
Lys Leu 275 280 285Ala Cys Thr Pro
Ser Leu Ile Arg Ala Gly Ser Arg Val Ala Tyr Arg 290
295 300Pro Ile Ser Ala Ser Val Leu Ser Arg Pro Glu Ala
Ser Arg Thr Gly305 310 315
320Glu Gly Ser Thr Val Phe Asn Gly Ala Gln Asn Gly Val Ser Gln Leu
325 330 335Ile Gln Arg Glu Phe
Gln Thr Ser Ala Ile Ser Arg 340
345153185PRTArtificial SequencencATP9_zmLOC100282174 153Met Ala Ser Thr
Arg Val Leu Ala Ser Arg Leu Ala Ser Gln Met Ala1 5
10 15Ala Ser Ala Lys Val Ala Arg Pro Ala Val
Arg Val Ala Gln Val Ser 20 25
30Lys Arg Thr Ile Gln Thr Gly Ser Pro Leu Gln Thr Leu Lys Arg Thr
35 40 45Gln Met Thr Ser Ile Val Asn Ala
Thr Thr Arg Gln Ala Phe Gln Lys 50 55
60Arg Ala Met Ala Leu Leu Arg Ala Ala Val Ser Glu Leu Arg Arg Arg65
70 75 80Gly Arg Gly Ala Leu
Thr Pro Leu Pro Ala Leu Ser Ser Leu Leu Ser 85
90 95Ser Leu Ser Pro Arg Ser Pro Ala Ser Thr Arg
Pro Glu Pro Asn Asn 100 105
110Pro His Ala Asp Arg Arg His Val Ile Ala Leu Arg Arg Cys Pro Pro
115 120 125Leu Pro Ala Ser Ala Val Leu
Ala Pro Glu Leu Leu His Ala Arg Gly 130 135
140Leu Leu Pro Arg His Trp Ser His Ala Ser Pro Leu Ser Thr Ser
Ser145 150 155 160Ser Ser
Ser Arg Pro Ala Asp Lys Ala Gln Leu Thr Trp Val Asp Lys
165 170 175Trp Ile Pro Glu Ala Ala Arg
Pro Tyr 180 185154455PRTArtificial
SequencehsADCK3_zmLOC100282174_crATP6_hsATP5G3 154Met Ala Ala Ile Leu Gly
Asp Thr Ile Met Val Ala Lys Gly Leu Val1 5
10 15Lys Leu Thr Gln Ala Ala Val Glu Thr His Leu Gln
His Leu Gly Ile 20 25 30Gly
Gly Glu Leu Ile Met Ala Ala Arg Ala Leu Gln Ser Thr Ala Val 35
40 45Glu Gln Ile Gly Met Phe Leu Gly Lys
Val Gln Gly Gln Asp Lys His 50 55
60Glu Glu Tyr Phe Ala Glu Asn Phe Gly Gly Pro Glu Gly Glu Phe His65
70 75 80Phe Ser Val Pro His
Ala Ala Gly Ala Ser Thr Asp Phe Ser Ser Ala 85
90 95Ser Ala Pro Asp Gln Ser Ala Pro Pro Ser Leu
Gly His Ala His Ser 100 105
110Glu Gly Pro Ala Pro Ala Tyr Val Ala Ser Gly Pro Phe Arg Glu Ala
115 120 125Gly Phe Pro Gly Gln Ala Ser
Ser Pro Leu Gly Arg Ala Asn Gly Arg 130 135
140Leu Phe Ala Asn Pro Arg Asp Ser Phe Ser Ala Met Gly Phe Gln
Arg145 150 155 160Arg Phe
Met Ala Leu Leu Arg Ala Ala Val Ser Glu Leu Arg Arg Arg
165 170 175Gly Arg Gly Ala Leu Thr Pro
Leu Pro Ala Leu Ser Ser Leu Leu Ser 180 185
190Ser Leu Ser Pro Arg Ser Pro Ala Ser Thr Arg Pro Glu Pro
Asn Asn 195 200 205Pro His Ala Asp
Arg Arg His Val Ile Ala Leu Arg Arg Cys Pro Pro 210
215 220Leu Pro Ala Ser Ala Val Leu Ala Pro Glu Leu Leu
His Ala Arg Gly225 230 235
240Leu Leu Pro Arg His Trp Ser His Ala Ser Pro Leu Ser Thr Ser Ser
245 250 255Ser Ser Ser Arg Pro
Ala Asp Lys Ala Gln Leu Thr Trp Val Asp Lys 260
265 270Trp Ile Pro Glu Ala Ala Arg Pro Tyr Met Ala Leu
Gln Gln Ala Ala 275 280 285Pro Arg
Val Phe Gly Leu Leu Gly Arg Ala Pro Val Ala Leu Gly Gln 290
295 300Ser Gly Ile Leu Thr Gly Ser Ser Gly Phe Lys
Asn Gln Gly Phe Asn305 310 315
320Gly Ser Leu Gln Ser Val Glu Asn His Val Tyr Ala Gln Ala Phe Ser
325 330 335Thr Ser Ser Gln
Glu Glu Gln Ala Ala Pro Ser Ile Gln Gly Ala Ser 340
345 350Gly Met Lys Leu Pro Gly Met Ala Gly Ser Met
Leu Leu Gly Lys Ser 355 360 365Arg
Ser Gly Leu Arg Thr Gly Ser Met Val Pro Phe Ala Ala Gln Gln 370
375 380Ala Met Asn Met Met Phe Ala Cys Ala Lys
Leu Ala Cys Thr Pro Ser385 390 395
400Leu Ile Arg Ala Gly Ser Arg Val Ala Tyr Arg Pro Ile Ser Ala
Ser 405 410 415Val Leu Ser
Arg Pro Glu Ala Ser Arg Thr Gly Glu Gly Ser Thr Val 420
425 430Phe Asn Gly Ala Gln Asn Gly Val Ser Gln
Leu Ile Gln Arg Glu Phe 435 440
445Gln Thr Ser Ala Ile Ser Arg 450
455155455PRTArtificial SequencecrATP6 _hsADCK3_zmLOC100282174_hsATP5G3
155Met Ala Leu Gln Gln Ala Ala Pro Arg Val Phe Gly Leu Leu Gly Arg1
5 10 15Ala Pro Val Ala Leu Gly
Gln Ser Gly Ile Leu Thr Gly Ser Ser Gly 20 25
30Phe Lys Asn Gln Gly Phe Asn Gly Ser Leu Gln Ser Val
Glu Asn His 35 40 45Val Tyr Ala
Gln Ala Phe Ser Thr Ser Ser Gln Glu Glu Gln Ala Ala 50
55 60Pro Ser Ile Gln Gly Ala Ser Gly Met Lys Leu Pro
Gly Met Ala Gly65 70 75
80Ser Met Leu Leu Gly Lys Ser Arg Ser Gly Leu Arg Thr Gly Ser Met
85 90 95Val Pro Phe Ala Ala Gln
Gln Ala Met Asn Met Met Ala Ala Ile Leu 100
105 110Gly Asp Thr Ile Met Val Ala Lys Gly Leu Val Lys
Leu Thr Gln Ala 115 120 125Ala Val
Glu Thr His Leu Gln His Leu Gly Ile Gly Gly Glu Leu Ile 130
135 140Met Ala Ala Arg Ala Leu Gln Ser Thr Ala Val
Glu Gln Ile Gly Met145 150 155
160Phe Leu Gly Lys Val Gln Gly Gln Asp Lys His Glu Glu Tyr Phe Ala
165 170 175Glu Asn Phe Gly
Gly Pro Glu Gly Glu Phe His Phe Ser Val Pro His 180
185 190Ala Ala Gly Ala Ser Thr Asp Phe Ser Ser Ala
Ser Ala Pro Asp Gln 195 200 205Ser
Ala Pro Pro Ser Leu Gly His Ala His Ser Glu Gly Pro Ala Pro 210
215 220Ala Tyr Val Ala Ser Gly Pro Phe Arg Glu
Ala Gly Phe Pro Gly Gln225 230 235
240Ala Ser Ser Pro Leu Gly Arg Ala Asn Gly Arg Leu Phe Ala Asn
Pro 245 250 255Arg Asp Ser
Phe Ser Ala Met Gly Phe Gln Arg Arg Phe Met Ala Leu 260
265 270Leu Arg Ala Ala Val Ser Glu Leu Arg Arg
Arg Gly Arg Gly Ala Leu 275 280
285Thr Pro Leu Pro Ala Leu Ser Ser Leu Leu Ser Ser Leu Ser Pro Arg 290
295 300Ser Pro Ala Ser Thr Arg Pro Glu
Pro Asn Asn Pro His Ala Asp Arg305 310
315 320Arg His Val Ile Ala Leu Arg Arg Cys Pro Pro Leu
Pro Ala Ser Ala 325 330
335Val Leu Ala Pro Glu Leu Leu His Ala Arg Gly Leu Leu Pro Arg His
340 345 350Trp Ser His Ala Ser Pro
Leu Ser Thr Ser Ser Ser Ser Ser Arg Pro 355 360
365Ala Asp Lys Ala Gln Leu Thr Trp Val Asp Lys Trp Ile Pro
Glu Ala 370 375 380Ala Arg Pro Tyr Met
Phe Ala Cys Ala Lys Leu Ala Cys Thr Pro Ser385 390
395 400Leu Ile Arg Ala Gly Ser Arg Val Ala Tyr
Arg Pro Ile Ser Ala Ser 405 410
415Val Leu Ser Arg Pro Glu Ala Ser Arg Thr Gly Glu Gly Ser Thr Val
420 425 430Phe Asn Gly Ala Gln
Asn Gly Val Ser Gln Leu Ile Gln Arg Glu Phe 435
440 445Gln Thr Ser Ala Ile Ser Arg 450
455156285PRTArtificial SequencehsADCK3_zmLOC100282174 156Met Ala Ala Ile
Leu Gly Asp Thr Ile Met Val Ala Lys Gly Leu Val1 5
10 15Lys Leu Thr Gln Ala Ala Val Glu Thr His
Leu Gln His Leu Gly Ile 20 25
30Gly Gly Glu Leu Ile Met Ala Ala Arg Ala Leu Gln Ser Thr Ala Val
35 40 45Glu Gln Ile Gly Met Phe Leu Gly
Lys Val Gln Gly Gln Asp Lys His 50 55
60Glu Glu Tyr Phe Ala Glu Asn Phe Gly Gly Pro Glu Gly Glu Phe His65
70 75 80Phe Ser Val Pro His
Ala Ala Gly Ala Ser Thr Asp Phe Ser Ser Ala 85
90 95Ser Ala Pro Asp Gln Ser Ala Pro Pro Ser Leu
Gly His Ala His Ser 100 105
110Glu Gly Pro Ala Pro Ala Tyr Val Ala Ser Gly Pro Phe Arg Glu Ala
115 120 125Gly Phe Pro Gly Gln Ala Ser
Ser Pro Leu Gly Arg Ala Asn Gly Arg 130 135
140Leu Phe Ala Asn Pro Arg Asp Ser Phe Ser Ala Met Gly Phe Gln
Arg145 150 155 160Arg Phe
Gly Gly Met Ala Leu Leu Arg Ala Ala Val Ser Glu Leu Arg
165 170 175Arg Arg Gly Arg Gly Ala Leu
Thr Pro Leu Pro Ala Leu Ser Ser Leu 180 185
190Leu Ser Ser Leu Ser Pro Arg Ser Pro Ala Ser Thr Arg Pro
Glu Pro 195 200 205Asn Asn Pro His
Ala Asp Arg Arg His Val Ile Ala Leu Arg Arg Cys 210
215 220Pro Pro Leu Pro Ala Ser Ala Val Leu Ala Pro Glu
Leu Leu His Ala225 230 235
240Arg Gly Leu Leu Pro Arg His Trp Ser His Ala Ser Pro Leu Ser Thr
245 250 255Ser Ser Ser Ser Ser
Arg Pro Ala Asp Lys Ala Gln Leu Thr Trp Val 260
265 270Asp Lys Trp Ile Pro Glu Ala Ala Arg Pro Tyr Gly
Gly 275 280 285157394PRTArtificial
SequencehsADCK3_zmLOC100282174_crATP6 157Met Ala Ala Ile Leu Gly Asp Thr
Ile Met Val Ala Lys Gly Leu Val1 5 10
15Lys Leu Thr Gln Ala Ala Val Glu Thr His Leu Gln His Leu
Gly Ile 20 25 30Gly Gly Glu
Leu Ile Met Ala Ala Arg Ala Leu Gln Ser Thr Ala Val 35
40 45Glu Gln Ile Gly Met Phe Leu Gly Lys Val Gln
Gly Gln Asp Lys His 50 55 60Glu Glu
Tyr Phe Ala Glu Asn Phe Gly Gly Pro Glu Gly Glu Phe His65
70 75 80Phe Ser Val Pro His Ala Ala
Gly Ala Ser Thr Asp Phe Ser Ser Ala 85 90
95Ser Ala Pro Asp Gln Ser Ala Pro Pro Ser Leu Gly His
Ala His Ser 100 105 110Glu Gly
Pro Ala Pro Ala Tyr Val Ala Ser Gly Pro Phe Arg Glu Ala 115
120 125Gly Phe Pro Gly Gln Ala Ser Ser Pro Leu
Gly Arg Ala Asn Gly Arg 130 135 140Leu
Phe Ala Asn Pro Arg Asp Ser Phe Ser Ala Met Gly Phe Gln Arg145
150 155 160Arg Phe Gly Gly Met Ala
Leu Leu Arg Ala Ala Val Ser Glu Leu Arg 165
170 175Arg Arg Gly Arg Gly Ala Leu Thr Pro Leu Pro Ala
Leu Ser Ser Leu 180 185 190Leu
Ser Ser Leu Ser Pro Arg Ser Pro Ala Ser Thr Arg Pro Glu Pro 195
200 205Asn Asn Pro His Ala Asp Arg Arg His
Val Ile Ala Leu Arg Arg Cys 210 215
220Pro Pro Leu Pro Ala Ser Ala Val Leu Ala Pro Glu Leu Leu His Ala225
230 235 240Arg Gly Leu Leu
Pro Arg His Trp Ser His Ala Ser Pro Leu Ser Thr 245
250 255Ser Ser Ser Ser Ser Arg Pro Ala Asp Lys
Ala Gln Leu Thr Trp Val 260 265
270Asp Lys Trp Ile Pro Glu Ala Ala Arg Pro Tyr Gly Gly Met Ala Leu
275 280 285Gln Gln Ala Ala Pro Arg Val
Phe Gly Leu Leu Gly Arg Ala Pro Val 290 295
300Ala Leu Gly Gln Ser Gly Ile Leu Thr Gly Ser Ser Gly Phe Lys
Asn305 310 315 320Gln Gly
Phe Asn Gly Ser Leu Gln Ser Val Glu Asn His Val Tyr Ala
325 330 335Gln Ala Phe Ser Thr Ser Ser
Gln Glu Glu Gln Ala Ala Pro Ser Ile 340 345
350Gln Gly Ala Ser Gly Met Lys Leu Pro Gly Met Ala Gly Ser
Met Leu 355 360 365Leu Gly Lys Ser
Arg Ser Gly Leu Arg Thr Gly Ser Met Val Pro Phe 370
375 380Ala Ala Gln Gln Ala Met Asn Met Gly Gly385
390158574PRTArtificial
SequencencATP9_zmLOC100282174_spilv1_GNFP_ncATP9 158Met Ala Ser Thr Arg
Val Leu Ala Ser Arg Leu Ala Ser Gln Met Ala1 5
10 15Ala Ser Ala Lys Val Ala Arg Pro Ala Val Arg
Val Ala Gln Val Ser 20 25
30Lys Arg Thr Ile Gln Thr Gly Ser Pro Leu Gln Thr Leu Lys Arg Thr
35 40 45Gln Met Thr Ser Ile Val Asn Ala
Thr Thr Arg Gln Ala Phe Gln Lys 50 55
60Arg Ala Met Ala Leu Leu Arg Ala Ala Val Ser Glu Leu Arg Arg Arg65
70 75 80Gly Arg Gly Ala Leu
Thr Pro Leu Pro Ala Leu Ser Ser Leu Leu Ser 85
90 95Ser Leu Ser Pro Arg Ser Pro Ala Ser Thr Arg
Pro Glu Pro Asn Asn 100 105
110Pro His Ala Asp Arg Arg His Val Ile Ala Leu Arg Arg Cys Pro Pro
115 120 125Leu Pro Ala Ser Ala Val Leu
Ala Pro Glu Leu Leu His Ala Arg Gly 130 135
140Leu Leu Pro Arg His Trp Ser His Ala Ser Pro Leu Ser Thr Ser
Ser145 150 155 160Ser Ser
Ser Arg Pro Ala Asp Lys Ala Gln Leu Thr Trp Val Asp Lys
165 170 175Trp Ile Pro Glu Ala Ala Arg
Pro Tyr Met Thr Val Leu Ala Pro Leu 180 185
190Arg Arg Leu His Thr Arg Ala Ala Phe Ser Ser Tyr Gly Arg
Glu Ile 195 200 205Ala Leu Gln Lys
Arg Phe Leu Asn Leu Asn Ser Cys Ser Ala Val Arg 210
215 220Arg Tyr Gly Thr Gly Phe Ser Asn Asn Leu Arg Ile
Lys Lys Leu Lys225 230 235
240Asn Ala Phe Gly Val Val Arg Ala Asn Ser Thr Lys Ser Thr Ser Thr
245 250 255Val Thr Thr Ala Ser
Pro Ile Lys Tyr Asp Ser Ser Phe Val Gly Lys 260
265 270Thr Gly Gly Glu Ile Phe His Asp Met Met Leu Lys
His Asn Val Lys 275 280 285His Val
Phe Gly Tyr Pro Gly Gly Ala Ile Leu Pro Val Phe Asp Ala 290
295 300Ile Tyr Arg Ser Pro His Phe Glu Phe Ile Leu
Pro Arg His Glu Gln305 310 315
320Ala Ala Gly His Ala Val Ser Gly Glu Gly Asp Ala Thr Tyr Gly Lys
325 330 335Leu Thr Leu Lys
Phe Ile Cys Thr Thr Gly Lys Leu Pro Val Pro Trp 340
345 350Pro Thr Leu Val Thr Thr Leu Thr Tyr Gly Val
Gln Cys Phe Ser Arg 355 360 365Tyr
Pro Asp His Met Lys Gln His Asp Phe Phe Lys Ser Ala Met Pro 370
375 380Glu Gly Tyr Val Gln Glu Arg Thr Ile Phe
Phe Lys Asp Asp Gly Asn385 390 395
400Tyr Lys Thr Arg Ala Glu Val Lys Phe Glu Gly Asp Thr Leu Val
Asn 405 410 415Arg Ile Glu
Leu Lys Gly Ile Asp Phe Lys Glu Asp Gly Asn Ile Leu 420
425 430Gly His Lys Leu Glu Tyr Asn Tyr Asn Ser
His Asn Val Tyr Ile Met 435 440
445Ala Asp Lys Gln Lys Asn Gly Ile Lys Val Asn Phe Lys Ile Arg His 450
455 460Asn Ile Glu Asp Gly Ser Val Gln
Leu Ala Asp His Tyr Gln Gln Asn465 470
475 480Thr Pro Ile Gly Asp Gly Pro Val Leu Leu Pro Asp
Asn His Tyr Leu 485 490
495Ser Thr Gln Ser Ala Leu Ser Lys Asp Pro Asn Glu Met Ala Ser Thr
500 505 510Arg Val Leu Ala Ser Arg
Leu Ala Ser Gln Met Ala Ala Ser Ala Lys 515 520
525Val Ala Arg Pro Ala Val Arg Val Ala Gln Val Ser Lys Arg
Thr Ile 530 535 540Gln Thr Gly Ser Pro
Leu Gln Thr Leu Lys Arg Thr Gln Met Thr Ser545 550
555 560Ile Val Asn Ala Thr Thr Arg Gln Ala Phe
Gln Lys Arg Ala 565 570159810PRTArtificial
SequencencATP9_zmLOC100282174_spilv1_lcSirt5_
osP0644B06.24-2_hsATP5G2_ncATP9 159Met Ala Ser Thr Arg Val Leu Ala Ser
Arg Leu Ala Ser Gln Met Ala1 5 10
15Ala Ser Ala Lys Val Ala Arg Pro Ala Val Arg Val Ala Gln Val
Ser 20 25 30Lys Arg Thr Ile
Gln Thr Gly Ser Pro Leu Gln Thr Leu Lys Arg Thr 35
40 45Gln Met Thr Ser Ile Val Asn Ala Thr Thr Arg Gln
Ala Phe Gln Lys 50 55 60Arg Ala Met
Ala Leu Leu Arg Ala Ala Val Ser Glu Leu Arg Arg Arg65 70
75 80Gly Arg Gly Ala Leu Thr Pro Leu
Pro Ala Leu Ser Ser Leu Leu Ser 85 90
95Ser Leu Ser Pro Arg Ser Pro Ala Ser Thr Arg Pro Glu Pro
Asn Asn 100 105 110Pro His Ala
Asp Arg Arg His Val Ile Ala Leu Arg Arg Cys Pro Pro 115
120 125Leu Pro Ala Ser Ala Val Leu Ala Pro Glu Leu
Leu His Ala Arg Gly 130 135 140Leu Leu
Pro Arg His Trp Ser His Ala Ser Pro Leu Ser Thr Ser Ser145
150 155 160Ser Ser Ser Arg Pro Ala Asp
Lys Ala Gln Leu Thr Trp Val Asp Lys 165
170 175Trp Ile Pro Glu Ala Ala Arg Pro Tyr Met Thr Val
Leu Ala Pro Leu 180 185 190Arg
Arg Leu His Thr Arg Ala Ala Phe Ser Ser Tyr Gly Arg Glu Ile 195
200 205Ala Leu Gln Lys Arg Phe Leu Asn Leu
Asn Ser Cys Ser Ala Val Arg 210 215
220Arg Tyr Gly Thr Gly Phe Ser Asn Asn Leu Arg Ile Lys Lys Leu Lys225
230 235 240Asn Ala Phe Gly
Val Val Arg Ala Asn Ser Thr Lys Ser Thr Ser Thr 245
250 255Val Thr Thr Ala Ser Pro Ile Lys Tyr Asp
Ser Ser Phe Val Gly Lys 260 265
270Thr Gly Gly Glu Ile Phe His Asp Met Met Leu Lys His Asn Val Lys
275 280 285His Val Phe Gly Tyr Pro Gly
Gly Ala Ile Leu Pro Val Phe Asp Ala 290 295
300Ile Tyr Arg Ser Pro His Phe Glu Phe Ile Leu Pro Arg His Glu
Gln305 310 315 320Ala Ala
Gly His Ala Met Arg Lys Arg Ser Leu Arg Cys His Leu Trp
325 330 335Ser Ala Asn Ala Ser Leu Ser
Pro Arg Lys Asp Glu Val Thr Ser Arg 340 345
350Lys Glu Ser Glu Asn Leu Val Lys Gly Lys Lys Asn Lys Lys
Ser His 355 360 365Leu His Leu Leu
Leu Phe Thr Ala Ser Lys Ile Gly Thr Asp Ser Val 370
375 380Phe Asp Val Gln Lys Ser Lys Glu Cys Cys Lys Glu
Leu Gly Leu Leu385 390 395
400Phe Thr Ser Leu Ile His Ser Ile Gly Ser Phe Pro Phe Asp Glu Glu
405 410 415Pro Lys Ala Ala Ala
Val Phe Leu Pro Gly Ser Leu Pro Gln Leu Thr 420
425 430Val Leu Val Leu Ala Pro Gly Ser Gly Ser Cys Pro
Thr Gly Lys Ser 435 440 445Thr Pro
His Leu Ala Ala Ser Gly Arg Asn Ala Glu Leu Leu Arg Pro 450
455 460Gln Asn Ser Met Ile Val Arg Gln Phe Thr Cys
Arg Gly Thr Ile Ser465 470 475
480Ser His Leu Cys Ala His Leu Arg Lys Pro His Asp Ser Arg Asn Met
485 490 495Ala Arg Pro Met
Ala Leu Leu Leu Arg His Ser Pro Lys Leu Arg Arg 500
505 510Ala His Ala Ile Leu Gly Cys Glu Arg Gly Thr
Val Val Arg His Phe 515 520 525Ser
Ser Ser Thr Cys Ser Ser Leu Val Lys Glu Asp Thr Val Ser Ser 530
535 540Ser Asn Leu His Pro Glu Tyr Ala Lys Lys
Ile Gly Gly Ser Asp Phe545 550 555
560Ser His Asp Arg Gln Ser Gly Lys Glu Leu Gln Asn Phe Lys Val
Ser 565 570 575Pro Gln Glu
Ala Ser Arg Ala Ser Asn Phe Met Arg Ala Ser Lys Tyr 580
585 590Gly Met Pro Ile Thr Ala Asn Gly Val His
Ser Leu Phe Ser Cys Gly 595 600
605Gln Val Val Pro Ser Arg Cys Phe Met Pro Glu Leu Ile Leu Tyr Val 610
615 620Ala Ile Thr Leu Ser Val Ala Glu
Arg Leu Val Gly Pro Gly His Ala625 630
635 640Cys Ala Glu Pro Ser Phe Arg Ser Ser Arg Cys Ser
Ala Pro Leu Cys 645 650
655Leu Leu Cys Ser Gly Ser Ser Ser Pro Ala Thr Ala Pro His Pro Leu
660 665 670Lys Met Phe Ala Cys Ser
Lys Phe Val Ser Thr Pro Ser Leu Val Lys 675 680
685Ser Thr Ser Gln Leu Leu Ser Arg Pro Leu Ser Ala Val Val
Leu Lys 690 695 700Arg Pro Glu Ile Leu
Thr Asp Glu Ser Leu Ser Ser Leu Ala Val Ser705 710
715 720Cys Pro Leu Thr Ser Leu Val Ser Ser Arg
Ser Phe Gln Thr Ser Ala 725 730
735Ile Ser Arg Asp Ile Asp Thr Ala Met Ala Ser Thr Arg Val Leu Ala
740 745 750Ser Arg Leu Ala Ser
Gln Met Ala Ala Ser Ala Lys Val Ala Arg Pro 755
760 765Ala Val Arg Val Ala Gln Val Ser Lys Arg Thr Ile
Gln Thr Gly Ser 770 775 780Pro Leu Gln
Thr Leu Lys Arg Thr Gln Met Thr Ser Ile Val Asn Ala785
790 795 800Thr Thr Arg Gln Ala Phe Gln
Lys Arg Ala 805 810160459PRTHomo sapiens
160Met Leu Lys Leu Ile Val Pro Thr Ile Met Leu Leu Pro Leu Thr Trp1
5 10 15Leu Ser Lys Lys His Met
Ile Trp Ile Asn Thr Thr Thr His Ser Leu 20 25
30Ile Ile Ser Ile Ile Pro Leu Leu Phe Phe Asn Gln Ile
Asn Asn Asn 35 40 45Leu Phe Ser
Cys Ser Pro Thr Phe Ser Ser Asp Pro Leu Thr Thr Pro 50
55 60Leu Leu Met Leu Thr Thr Trp Leu Leu Pro Leu Thr
Ile Met Ala Ser65 70 75
80Gln Arg His Leu Ser Ser Glu Pro Leu Ser Arg Lys Lys Leu Tyr Leu
85 90 95Ser Met Leu Ile Ser Leu
Gln Ile Ser Leu Ile Met Thr Phe Thr Ala 100
105 110Thr Glu Leu Ile Met Phe Tyr Ile Phe Phe Glu Thr
Thr Leu Ile Pro 115 120 125Thr Leu
Ala Ile Ile Thr Arg Trp Gly Asn Gln Pro Glu Arg Leu Asn 130
135 140Ala Gly Thr Tyr Phe Leu Phe Tyr Thr Leu Val
Gly Ser Leu Pro Leu145 150 155
160Leu Ile Ala Leu Ile Tyr Thr His Asn Thr Leu Gly Ser Leu Asn Ile
165 170 175Leu Leu Leu Thr
Leu Thr Ala Gln Glu Leu Ser Asn Ser Trp Ala Asn 180
185 190Asn Leu Met Trp Leu Ala Tyr Thr Met Ala Phe
Met Val Lys Met Pro 195 200 205Leu
Tyr Gly Leu His Leu Trp Leu Pro Lys Ala His Val Glu Ala Pro 210
215 220Ile Ala Gly Ser Met Val Leu Ala Ala Val
Leu Leu Lys Leu Gly Gly225 230 235
240Tyr Gly Met Met Arg Leu Thr Leu Ile Leu Asn Pro Leu Thr Lys
His 245 250 255Met Ala Tyr
Pro Phe Leu Val Leu Ser Leu Trp Gly Met Ile Met Thr 260
265 270Ser Ser Ile Cys Leu Arg Gln Thr Asp Leu
Lys Ser Leu Ile Ala Tyr 275 280
285Ser Ser Ile Ser His Met Ala Leu Val Val Thr Ala Ile Leu Ile Gln 290
295 300Thr Pro Trp Ser Phe Thr Gly Ala
Val Ile Leu Met Ile Ala His Gly305 310
315 320Leu Thr Ser Ser Leu Leu Phe Cys Leu Ala Asn Ser
Asn Tyr Glu Arg 325 330
335Thr His Ser Arg Ile Met Ile Leu Ser Gln Gly Leu Gln Thr Leu Leu
340 345 350Pro Leu Met Ala Phe Trp
Trp Leu Leu Ala Ser Leu Ala Asn Leu Ala 355 360
365Leu Pro Pro Thr Ile Asn Leu Leu Gly Glu Leu Ser Val Leu
Val Thr 370 375 380Thr Phe Ser Trp Ser
Asn Ile Thr Leu Leu Leu Thr Gly Leu Asn Met385 390
395 400Leu Val Thr Ala Leu Tyr Ser Leu Tyr Met
Phe Thr Thr Thr Gln Trp 405 410
415Gly Ser Leu Thr His His Ile Asn Asn Met Lys Pro Ser Phe Thr Arg
420 425 430Glu Asn Thr Leu Met
Phe Met His Leu Ser Pro Ile Leu Leu Leu Ser 435
440 445Leu Asn Pro Asp Ile Ile Thr Gly Phe Ser Ser 450
455161174PRTHomo sapiens 161Met Met Tyr Ala Leu Phe Leu
Leu Ser Val Gly Leu Val Met Gly Phe1 5 10
15Val Gly Phe Ser Ser Lys Pro Ser Pro Ile Tyr Gly Gly
Leu Val Leu 20 25 30Ile Val
Ser Gly Val Val Gly Cys Val Ile Ile Leu Asn Phe Gly Gly 35
40 45Gly Tyr Met Gly Leu Met Val Phe Leu Ile
Tyr Leu Gly Gly Met Met 50 55 60Val
Val Phe Gly Tyr Thr Thr Ala Met Ala Ile Glu Glu Tyr Pro Glu65
70 75 80Ala Trp Gly Ser Gly Val
Glu Val Leu Val Ser Val Leu Val Gly Leu 85
90 95Ala Met Glu Val Gly Leu Val Leu Trp Val Lys Glu
Tyr Asp Gly Val 100 105 110Val
Val Val Val Asn Phe Asn Ser Val Gly Ser Trp Met Ile Tyr Glu 115
120 125Gly Glu Gly Ser Gly Leu Ile Arg Glu
Asp Pro Ile Gly Ala Gly Ala 130 135
140Leu Tyr Asp Tyr Gly Arg Trp Leu Val Val Val Thr Gly Trp Thr Leu145
150 155 160Phe Val Gly Val
Tyr Ile Val Ile Glu Ile Ala Arg Gly Asn 165
170162318PRTHomo sapiens 162Met Pro Met Ala Asn Leu Leu Leu Leu Ile Val
Pro Ile Leu Ile Ala1 5 10
15Met Ala Phe Leu Met Leu Thr Glu Arg Lys Ile Leu Gly Tyr Met Gln
20 25 30Leu Arg Lys Gly Pro Asn Val
Val Gly Pro Tyr Gly Leu Leu Gln Pro 35 40
45Phe Ala Asp Ala Met Lys Leu Phe Thr Lys Glu Pro Leu Lys Pro
Ala 50 55 60Thr Ser Thr Ile Thr Leu
Tyr Ile Thr Ala Pro Thr Leu Ala Leu Thr65 70
75 80Ile Ala Leu Leu Leu Trp Thr Pro Leu Pro Met
Pro Asn Pro Leu Val 85 90
95Asn Leu Asn Leu Gly Leu Leu Phe Ile Leu Ala Thr Ser Ser Leu Ala
100 105 110Val Tyr Ser Ile Leu Trp
Ser Gly Trp Ala Ser Asn Ser Asn Tyr Ala 115 120
125Leu Ile Gly Ala Leu Arg Ala Val Ala Gln Thr Ile Ser Tyr
Glu Val 130 135 140Thr Leu Ala Ile Ile
Leu Leu Ser Thr Leu Leu Met Ser Gly Ser Phe145 150
155 160Asn Leu Ser Thr Leu Ile Thr Thr Gln Glu
His Leu Trp Leu Leu Leu 165 170
175Pro Ser Trp Pro Leu Ala Met Met Trp Phe Ile Ser Thr Leu Ala Glu
180 185 190Thr Asn Arg Thr Pro
Phe Asp Leu Ala Glu Gly Glu Ser Glu Leu Val 195
200 205Ser Gly Phe Asn Ile Glu Tyr Ala Ala Gly Pro Phe
Ala Leu Phe Phe 210 215 220Met Ala Glu
Tyr Thr Asn Ile Ile Met Met Asn Thr Leu Thr Thr Thr225
230 235 240Ile Phe Leu Gly Thr Thr Tyr
Asp Ala Leu Ser Pro Glu Leu Tyr Thr 245
250 255Thr Tyr Phe Val Thr Lys Thr Leu Leu Leu Thr Ser
Leu Phe Leu Trp 260 265 270Ile
Arg Thr Ala Tyr Pro Arg Phe Arg Tyr Asp Gln Leu Met His Leu 275
280 285Leu Trp Lys Asn Phe Leu Pro Leu Thr
Leu Ala Leu Leu Met Trp Tyr 290 295
300Val Ser Met Pro Ile Thr Ile Ser Ser Ile Pro Pro Gln Thr305
310 315163957DNAHomo sapiens 163atacccatgg ccaacctcct
actcctcatt gtacccattc taatcgcaat ggcattccta 60atgcttaccg aacgaaaaat
tctaggctat atacaactac gcaaaggccc caacgttgta 120ggcccctacg ggctactaca
acccttcgct gacgccataa aactcttcac caaagagccc 180ctaaaacccg ccacatctac
catcaccctc tacatcaccg ccccgacctt agctctcacc 240atcgctcttc tactatgaac
ccccctcccc atacccaacc ccctggtcaa cctcaaccta 300ggcctcctat ttattctagc
cacctctagc ctagccgttt actcaatcct ctgatcaggg 360tgagcatcaa actcaaacta
cgccctgatc ggcgcactgc gagcagtagc ccaaacaatc 420tcatatgaag tcaccctagc
catcattcta ctatcaacat tactaataag tggctccttt 480aacctctcca cccttatcac
aacacaagaa cacctctgat tactcctgcc atcatgaccc 540ttggccataa tatgatttat
ctccacacta gcagagacca accgaacccc cttcgacctt 600gccgaagggg agtccgaact
agtctcaggc ttcaacatcg aatacgccgc aggccccttc 660gccctattct tcatagccga
atacacaaac attattataa taaacaccct caccactaca 720atcttcctag gaacaacata
tgacgcactc tcccctgaac tctacacaac atattttgtc 780accaagaccc tacttctaac
ctccctgttc ttatgaattc gaacagcata cccccgattc 840cgctacgacc aactcataca
cctcctatga aaaaacttcc taccactcac cctagcatta 900cttatatgat atgtctccat
acccattaca atctccagca ttccccctca aacctaa 95716423DNAArtificial
SequenceND1-F primer 164gaggctctgt ctggtatctt gaa
2316518DNAArtificial SequenceND1-R primer
165gtcggggcgg tgatgtag
1816620DNAArtificial SequenceGAPDH-F primer 166cctgtacgcc aacacagtgc
2016720DNAArtificial
SequenceGAPDH-R primer 167atactcctgc ttgctgatcc
201681041DNAArtificial SequenceCOX10-opt_ND1
168atggccgcat ctccgcacac tctctcctca cgcctcctga caggttgcgt aggaggctct
60gtctggtatc ttgaaagaag aactatgccc atggccaacc tgctgctgct gatcgtgccc
120atcctgatcg ccatggcctt cctgatgctg accgagcgca agatcctggg ctacatgcag
180ctgcgcaagg gccccaacgt ggtgggcccc tacggcctgc tgcagccctt cgccgacgcc
240atgaagctgt tcaccaagga gcccctgaag cccgccacca gcaccatcac cctgtacatc
300accgccccca ccctggccct gaccatcgcc ctgctgctgt ggacccccct gcccatgccc
360aaccccctgg tgaacctgaa cctgggcctg ctgttcatcc tggccaccag cagcctggcc
420gtgtacagca tcctgtggag cggctgggcc agcaacagca actacgccct gatcggcgcc
480ctgcgcgccg tggcccagac catcagctac gaggtgaccc tggccatcat cctgctgagc
540accctgctga tgagcggcag cttcaacctg agcaccctga tcaccaccca ggagcacctg
600tggctgctgc tgcccagctg gcccctggcc atgatgtggt tcatcagcac cctggccgag
660accaaccgca cccccttcga cctggccgag ggcgagagcg agctggtgag cggcttcaac
720atcgagtacg ccgccggccc cttcgccctg ttcttcatgg ccgagtacac caacatcatc
780atgatgaaca ccctgaccac caccatcttc ctgggcacca cctacgacgc cctgagcccc
840gagctgtaca ccacctactt cgtgaccaag accctgctgc tgaccagcct gttcctgtgg
900atccgcaccg cctacccccg cttccgctac gaccagctga tgcacctgct gtggaagaac
960ttcctgcccc tgaccctggc cctgctgatg tggtacgtga gcatgcccat caccatcagc
1020agcatccccc cccagaccta a
10411691041DNAArtificial SequenceCOX10-ND1 169atggccgcat ctccgcacac
tctctcctca cgcctcctga caggttgcgt aggaggctct 60gtctggtatc ttgaaagaag
aactatgccc atggccaacc tcctactcct cattgtaccc 120attctaatcg caatggcatt
cctaatgctt accgaacgaa aaattctagg ctatatgcaa 180ctacgcaaag gccccaacgt
tgtaggcccc tacgggctac tacaaccctt cgctgacgcc 240atgaaactct tcaccaaaga
gcccctaaaa cccgccacat ctaccatcac cctctacatc 300accgccccga ccttagctct
caccatcgct cttctactat ggacccccct ccccatgccc 360aaccccctgg tcaacctcaa
cctaggcctc ctatttattc tagccacctc tagcctagcc 420gtttactcaa tcctctggtc
agggtgggca tcaaactcaa actacgccct gatcggcgca 480ctgcgagcag tagcccaaac
aatctcatat gaagtcaccc tagccatcat tctactatca 540acattactaa tgagtggctc
ctttaacctc tccaccctta tcacaacaca agaacacctc 600tggttactcc tgccatcatg
gcccttggcc atgatgtggt ttatctccac actagcagag 660accaaccgaa cccccttcga
ccttgccgaa ggggagtccg aactagtctc aggcttcaac 720atcgaatacg ccgcaggccc
cttcgcccta ttcttcatgg ccgaatacac aaacattatt 780atgatgaaca ccctcaccac
tacaatcttc ctaggaacaa catatgacgc actctcccct 840gaactctaca caacatattt
tgtcaccaag accctacttc taacctccct gttcttatgg 900attcgaacag catacccccg
attccgctac gaccaactca tgcacctcct atggaaaaac 960ttcctaccac tcaccctagc
attacttatg tggtatgtct ccatgcccat tacaatctcc 1020agcattcccc ctcaaaccta a
1041
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