MITOCHONDRIA REGULATOR COMPOSITION

Abstract

The present invention provides a mitochondria regulator composition, which comprises a wild bitter gourd extract. The mitochondria regulator composition can regulate the function of mitochondria in a cell, and further regulate the efficiency of adaptive thermogenesis and energy expenditure in a cell.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the priority of Taiwanese Patent Application No. 101129306, filed on Aug. 13, 2012, which is incorporated herewith by reference in its entirety.

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] The present invention relates to a cell regulator, especially relates to a mitochondria regulator.

[0004] 2. The Prior Arts

[0005] No matter at rest or at work, normal function of human organs and tissues must have adenosine triphosphate (abbreviated as ATP) involved. In cells about 90% of the ATP is generated by mitochondria, and oxygen is consumed when mitochondria produces ATP. It is estimated that 90% of the oxygen in the cell are used by mitochondria. Furthermore, when mitochondria metabolize three major nutrients (fatty acids, carbohydrates, and amino acids) efficiently, oxygen will be consumed no matter energy generated or heat generated. Therefore, mitochondria itself is high oxygen consuming organelle and mitochondria is the site with highest frequency of oxidation and reduction reactions in the cell.

[0006] In human cell, skeletal muscle use ATP most frequently. ATP required for muscle fiber contraction is dependent on vigorous oxidative phosphorylation reaction in mitochondria. Therefore, there are more blood vessels around the muscle fibers in order to provide enough oxygen and fuel molecules (i.e., fatty acids, carbohydrates, or amino acids).

[0007] In addition, fatty tissues in the body can be classified into two groups, namely white adipose tissue and brown adipose tissue, according to their mitochondria type, distribution site in the body and color. The white adipose tissue has smaller and less amount of mitochondria, and the fatty acids in the tissue serve as energy source during rest state and oxidative exercise. On the other hand, the brown adipose tissues are mainly distributed in the shoulder, neck and arm of hibernating animals, and have abundant of mitochondria. Because mitochondria contain many cell pigments, these pigments makes brown adipose tissue exhibits brown color.

[0008] Although oxidative metabolism in cellular mitochondria produces ATP, mitochondria in the brown adipose tissue are not designed to produce ATP as a mode of energy output. Especially, there are many thermogenin distributed on the inner membrane of mitochondria in the brown adipose tissue. The thermogenin is a protein that consumes all energy generated by oxidation of fuel molecules, thus no ATP can be generated. Instead, heat is produced and the energy is dissipated. Because the mitochondria in the brown adipose tissue are large and abundant, more heat is produced.

[0009] Therefore, brown adipose tissues rely on the unique heat generation system of mitochondria to oxidize fatty acids at low temperature or during ingestion. Without exercise, hibernating animals and newborn babies can also generate heat to adapt cold environment. Because the central temperature regulation system in the newborn babies is not mature, the heat production mode of brown adipose tissue is especially important to protect the newborn babies from tremble reaction. The thermogenin in the mitochondria of brown adipose tissue is an important factor to keep thermostasis.

[0010] The above thermogenin apply uncoupling reaction to reduce ATP generation in mitochondria, increase basic metabolism consumption and dissipate energy in heat form. Uncoupling protein (abbreviated as UCP) plays an important role as regulator in mitochondrial's uncoupling reaction. UCPs are proteins located in the inner membrane of mitochondria and there are three main expression forms, including UCP1, UCP2, and UCP3. UCP2 and UCP3 are mainly responsible for regulation of reactive oxygen species (ROS) synthesis. The expression levels of UCP2 and UCP3 are far less than that of UCP1 in mammals. UCP1, also called as "thermogenin", is mainly expressed in brown adipose tissue and is mainly responsible for adaptive regulation of heat generation and heat consumption.

[0011] Peroxisome proliferator-activated receptor γ coactivator-1 (PGC1α), tfam (mitochondrial transcription factor A) and NrF1 (nuclear respiratory factor 1) are important transcription regulation factors in mitochondria biosynthesis, wherein PGC1α is a coactivator of PPARγ that mainly distributed in high oxygen consumption tissue, such as heart tissues or brown adipose tissues. PGC1α can regulate mitochondria biosysthesis and energy metabolism. Furthermore, tfam can bind to mitochondria DNA to regulate mitochondria transcription and replication, and NrF1 is also involved in regulation of mitochondria gene transcription. Prior studies have shown that increase of PGC1αquadrature concentration in the muscle can stimulate expression of abovementioned NrF and tfam of mitochondria genes, decrease possibility of obesity owing to aging, and decrease possibility of diabetes, and prolong life.

[0012] The material, bitter gourd, is a common traditional Chinese medicine. However, to the best of our knowledge, the bitter gourd has never been reported in regulation the mitochondria. The mitochondria regulator can modulate mitochondrial related proteins and genes effectively to enhance heat and energy generation efficiency. The mitochondria regulator composition of the present invention can be used as a healthy food composition or pharmaceutical composition for treatment of disease due to deficiency of thermogenin or mitochondria, mitochondrial dysfunction, mitochondria malfunction, or mitochindria dysregulation.

SUMMARY OF THE INVENTION

[0013] However, the prior studies of bitter gourd mainly focused on reduction of blood sugar, anti-oxidation activity, and regulation of immune reaction. The present invention discloses that the bitter gourd has significant ability to regulate biosynthesis of intracellular mitochondria and to improve production of energy and heat.

[0014] Therefore, the present invention provides a mitochondria regulator composition for regulating a mitochondria in a cell, which consisting essentially of a bitter gourd extract. The cells can be a white adipose tissue cell, a brown adipose tissue cell, or a muscle cell. One embodiment of the present invention, the bitter gourd extract of the present invention is used at least 5% of total diet.

[0015] In one example of the present invention, the mitochondria regulator composition can enhance the expression of UCP1 gene (SEQ ID NO:9), PGC1α gene (SEQ ID NO:4), or NrF1 gene (SEQ ID NO:12) in the white adipose tissue cell.

[0016] In another example of the present invention, the mitochondria regulator composition can enhance the expression of PGC1α (SEQ ID NO:4) or NrF1 (SEQ ID NO:12) in the brown adipose tissue cell.

[0017] In another example of the present invention, the mitochondria regulator composition can enhance the expression of PGC1α gene (SEQ ID NO:4) or tfam gene (SEQ ID NO:13) in the muscle cell.

[0018] The present invention also provides a method of regulating a mitochondria in a cell, comprising administering to a subject an effective amount of a bitter gourd extract, wherein the cell can be a white adipose tissue cell, a brown adipose tissue or a muscle cell. In one example of the present invention, the bitter gourd extract is a freeze-dry powder of whole bitter gourd fruit.

[0019] Wherein, the bitter gourd extract can enhance the expression of UCP1 (SEQ ID NO:9), PGC1α (SEQ ID NO:4), or NrF1 (SEQ ID NO:12) to regulate mitochondria activity in the white adipose tissue; can enhance the expression of can enhance PGC1α (SEQ ID NO:4), or NrF1 (SEQ ID NO:12) to regulate mitochondria activity in the brown adipose tissue; and can enhance the expression of PGC1α (SEQ ID NO:4) or tfam (SEQ ID NO:13) to regulate mitochondria activity in the muscle cell.

[0020] Using the bitter gourd extract of the present invention, the function of intracellular mitochondria can be regulated by enhancement of mitochondria biosynthesis and generation of heat, which further leading to regulation of heat generation and energy consumption efficiency.

[0021] The present invention is further explained in the following embodiment illustration and examples. Those examples below should not, however, be considered to limit the scope of the invention, it is contemplated that modifications will readily occur to those skilled in the art, which modifications will be within the spirit of the invention and scope of the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

[0022] FIG. 1A shows the oxygen consumption per gram body weight (VO₂/gBW) of mice in 24 hours.

[0023] FIG. 1B shows a comparison of the area under curve of FIG. 1A.

[0024] FIG. 2A shows CO₂ production per gram body weight (VCO₂/gBW) of mice in 24 hours.

[0025] FIG. 2B shows a comparison of the area under curve of FIG. 2A.

[0026] FIG. 3A shows RQ value of mice in 24 hours.

[0027] FIG. 3B shows a comparison of the area under curve of FIG. 3A.

[0028] FIG. 4A shows gene expression in epididymal white adipose tissue (EWAT).

[0029] FIG. 4B shows gene expression in brown adipose tissue (BAT).

[0030] FIG. 4C shows gene expression in the muscle tissue.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

[0031] The present invention uses mice for study. Mice are divided into two groups, the control group and the experimental group. The diet of the experimental group contains 5% of wild bitter gourd powder, therefore, this group is also named as BGP group. The diet of the control group is a modification of AIN-93G basic diet, therefore, this group is also called Basal group.

[0032] Because increase of mitochondria biosynthesis and increase of heat and energy generation efficiency require consumption of oxygen, mice fed with experimental diet were monitored their oxygen consumption, CO₂ production, and respiratory quotient at week 5. The oxygen consumption, CO₂ production, and respiratory quotient of experimental group were compared with control group to examine if elevation trend was observed. If yes, further analysis of mRNA was conducted to determine if increase of mitochondria biosynthesis and increase of heat and energy generation efficiency contributed to elevation of oxygen consumption, CO₂ production, and respiratory quotient. mRNA analysis was conducted by sampling of white adipose tissue, gastrocnemius, and brown adipose tissue of experimental group mice at 22 week for mRNA and protein analysis. If the BGP group mice fed with diet incorporating 5% wild bitter gourd showed significant elevation of fatty acid oxidation, adapted heat generation, and gene or protein related to mitochondria biosynthesis, the results provided evidences that wild bitter gourd can enhance mitochondria biosynthesis and increase efficiency of heat and energy generation. The above described methods are further explained in the following examples.

[0033] Data of the present invention are presented as means±SD. Differences between the two groups of mice were analyzed by Student's t test. Data was transformed into log or root square before statistic analysis if they are not normally distributed. P value <0.05 was considered significant.

DEFINITION

[0034] The term "regulator" of the present invention is intended to mean capability to enhance or reduce an activity. Therefore, the mitochondria regulator composition of the present invention for use in regulation of mitochondria as described in the specification is intended to mean the use of the mitochondria regulator composition in direct contact with the mitochondria. In further examples, the mitochondria regulator composition of the present invention can be administered an effective amount to an individual when mitochondria require regulation to enhance or increase mitochondria activity.

Example 1

Diet Formulation of Bitter Gourd and Animal Study

[0035] Fresh wild bitter gourd (Cultivar Hualian No. 4) fruits were provided by Hualien District Agricultural Research and Extension Station of Taiwan. This cultivar was specifically bred based on a high PPAR activating activity. Whole fruits (included seeds) were washed, sliced, frozen and lyophilized. They were then grounded to produce the bitter gourd powder (BGP) sample and stored at -20° C. for making the BGP test diet.

[0036] Twelve eight-week old male C57BL/6J mice for animal studies were purchased from the National Laboratory Animal Center (Taipei, Taiwan). Mice were acclimatized for 4 weeks and fed a non-purified diet (Rodent Chow, PMI Nutrition International, Brentwood, Mo. USA) before the experiment. After acclimation, mice were randomly assigned into two groups. The control group (n=6) was fed AIN-93 modified basal diet wherein carbohydrate sources were provided by 50% sucrose (abbreviated as basal group), while the experimental group (n=6) was fed AIN-93 modified basal diet by incorporating 5% (w/w) of a freeze dried powder of bitter gourd (abbreviated as BGP group). Before the experiment began, the experimental mice were acclimated for bitter taste for one week. All experimental mice were housed individually in stainless steel wire cages in an animal room with a 12 hour light and 12 hour dark cycle and constant temperature (22±2° C.). Throughout the acclimation and experimental period, mice had free access to water and diet. Diet was changed twice a week, and each mice body weight was recorded every week.

[0037] The diet formulations described above are shown in Table 1 below. The basal diet was a modification of AIN-93G diet, wherein the original carbohydrate source (62.95% of corn starch) was replaced by mixture of corn starch (Samayang genex, Korea) and sucrose in 12.95:50 ratio. The rest ingredients include casein (ICN, USA), cystine (Wako, Japan), cellulose (JRS, Germany), AIN-93G Vitamin Mix (ICN, USA), AIN-93 Mineral Mix (ICN, USA) and choline (Sigma, USA). To prepare diet, powder materials were mixed well. Then soybean oil (Taiwan Sugar) was added and mixed again. After sieving twice, diet was packaged in double layer sealing bag and stored at -20° C. until use. The BGP diet was formulated by incorporating 5% (w/w) of BGP into the basal diet by slightly adjusting the composition of casein, corn starch, soybean oil and cellulose based on the proximate composition of BGP, i.e., crude protein 4.5%, carbohydrate 54.6%, cellulose 38.2% and crude fat 2.7%.

TABLE-US-00001 TABLE 1 Diet Formulation of Basal Group and BGP Group containing Freeze Dried Powder of Hualien No. 4 Bitter Gourd Composition % Basal Group BGP Group Casein 20 19.775 L-Cystine 0.3 0.3 Corn Starch 12.95 10.22 Sucrose 50 50 Cellulose 5 3.09 Soybean Oil 7 6.865 AIN-93G Vitamin Mix 1 1 AIN-93G Mineral Mix 3.5 3.5 Choline 0.25 0.25 Freeze Dried Powder of Hualien No. 4 Bitter -- 5 Gourd Oligosaccharide -- -- kcal/g 3.948 3.948 fiber/g 0.05 0.05 Energy of carbohydrate/total energy (%) 63.78 63.78 Energy of protein/total energy (%) 20.26 20.26 Lipid energy/total energy (%) 15.96 15.96 1. Diet of AIN-93 Vitamin Mix and AIN-93Mineral Mix are prepared according to formulation described in J. Nutr. 123: 1939-1951 (1993) (Reeves et al., 1993). 2. Diet of BGP group was prepared incorporating bitter gourd powder into basal AIN-93 basal diet by slightly adjusting the compositions.

Example 2

Oxygen Consumption, Carbon Dioxide Production, and Respiratory Quotient Measurement (Metabolic Chamber Study)

[0038] The mice of the example 1 were fed with experimental diet for 5 weeks. The mice were then acclimatized in Oxymax System metabolic chambers (AccuScan Instruments, Inc. Columbus, Ohio USA) for 6 days with free access to the respective diet and water in an animal room kept on a 12 hour light and 12 hour dark cycle (light phase 8:00-20:00; dark phase 20:00-8:00) until steady. After acclimatization, data of the O₂ consumption and CO₂ production of the mice were automatically monitored and recorded for 24 hours on day 7 and the results were expressed as per gram body weight. The respiratory quotients (RQ) were also calculated as VCO₂/VO₂.

[0039] The results showed that the experimental group (the BGP group) at different time point of dark phase (20:00-8:00) showed significant increase of oxygen consumption (FIG. 1A) and CO₂ production (FIG. 2A, p<0.05) per gram body weight. Further calculation of area under curve (abbreviated as AUC) of FIG. 1 and FIG. 2A indicated that the BGP group showed significant increase of oxygen consumption (FIG. 1B) and CO₂ production (FIG. 2B, p<0.05) in the dark phase as compared to basal group. The VCO₂ was further divided by VO₂. The obtained results, respiratory quotient (abbreviated as RQ values), were shown in FIGS. 3A and 3B. The RQ values of the BGP group were 0.8-0.9, whereas the RQ values of the basal group were 0.7-0.8. Compared to the basal group, mice in the BGP group had significantly higher VO₂ and VCO₂ at quite a few time points in the dark phase (p<0.05). However, there is no significant difference (p>0.05) between the BGP group and the basal group in oxygen consumption, CO₂ production, and RQ value when these groups were in the light phase (8:00-20:00).

[0040] Therefore, oxygen consumption, CO₂ production, and RQ value of the BGP group through the dark phase was significantly higher than that of the basal group, indicating that respiratory activity of the BGP group mice was higher in the dark phase and energy and heat generation efficiency of mitochondria in the BGP group mice has been enhanced. This assumption requires further gene expression analysis to provide objective evidences.

Example 3

Gene Expression Analysis

[0041] At the end of 22 week of feeding, mice were feed-deprived at 3 AM in the morning for 16 hours, weigh of body weight and then sacrificed by CO₂ asphyxiation. Excise and collect about 0.1 gram of epididymal white adipose tissue (abbreviated as EWAT), gastrocnemius muscle white adipose tissue and intra scapular brown adipose tissue in sterile 1.5 mL centrifuge tube or foil, then weighed and immediately frozen in liquid nitrogen, and then stored at -80° C. until gene expression analysis.

[0042] The mRNA expression of the following genes in epididymal white adipose tissue, brown adipose tissue (abbreviated as BAT) or muscle cells were analyzed, including PPARα (SEQ ID NO:1), PPARγ (SEQ ID NO:2), PPARδ (SEQ ID NO:3), and PGC1α (SEQ ID NO:4) genes; fatty acid oxidation related genes: CPT1a (SEQ ID NO:5), CPT1b (SEQ ID NO:6), ACD1 (SEQ ID NO:7), and ACS1 (SEQ ID NO:8); adaptive heat generation related gene: uncoupling protein 1 (UCP1 (SEQ ID NO:9)); cholesterol metabolism related gene and glycolysis related genes: SREBP1 (SEQ ID NO:10) and GK (SEQ ID NO:11); and mitochondria biosynthesis genes NrF1 (SEQ ID NO:12) and tfam (SEQ ID NO:13), wherein PCR primer and probes were purchased from Applied Biosystems.

[0043] RNA was isolated using TRIZOL reagent (Invitrogen) according to the instruction. Total RNA (2 μg) was reversed transcribed into cDNA in mixed solution containing 10× Rnt buffer, 100 mM dNTP mix buffer, 10×RT random primer, and MutiScribe® RTase. Total volume of the polymerase chain reaction (PCR) mixture was 25 μL, containing 10 μL cDNA, 12.5 μL TaqMan® Gene Expression Master Mix, 1.25 μL probe/primer reagent mixture and water. PCR and fluorescence analysis was performed using ABI PRISM7000 Gene Sequence Detection System. Amplification conditions 150 were: 2 min at 50° C., 10 min at 95° C. then 40 cycles of 15 s at 95° C. and 1 min at 60° C.

[0044] Referring to FIG. 4A, in the epididymal white adipose tissue, the BGP group showed significant increase (p<0.05) in expression of PPARγ (SEQ ID NO:2), PGC1α (SEQ ID NO:4), fatty acid oxidation gene (CPT1a (SEQ ID NO:5), ACD1 (SEQ ID NO:7)), and uncoupling protein gene 1 UCP1 (SEQ ID NO:9), and Mitochondria biosynthesis gene (NrF1 (SEQ ID NO:12)). Referring to FIG. 4B, in the brown adipose tissue the BGP group showed significant increase (p<0.05) of expression in PPARδ (SEQ ID NO: 3), PGC1α (SEQ ID NO:4) and NrF1 (SEQ ID NO:12) genes. Referring to FIG. 4C, in the gastrocnemius muscle the BGP group also showed significant increase of expression (p<0.05) of PGC1α (SEQ ID NO: 4), ACS1 (SEQ ID NO:8) and tfam (SEQ ID NO:13) genes.

[0045] In summary of the examples above, the results demonstrate that male C57BL/6J mice fed with experimental diet for 22 weeks (the BGP group) show significant increase of oxygen consumption, CO₂ production and AUCs. In the aspect of RQ value, the value of the BGP group is close to 1.0, compared to 0.7 of the Basal group. RQ value is the CO₂ produced (mole)/O₂ consumed (mole) when carbohydrates or fatty acids are metabolized. The RQ value of glucose oxidation is about 1 and RQ value of fatty acid is around 0.7. Therefore, the BGP group shows significant increase of carbohydrate oxidation when in the dieting phase (dark phase).

[0046] Experiments are designed to determine gene expression in gastrocnemius muscle, brown adipose tissue and epidiymal white adipose tissue. The results indicate that BGP group shows significant increase expression of PGC1α (SEQ ID NO: 4), fatty acid metabolism related gene CPT1a (SEQ ID NO: 5) and ACD1 (SEQ ID NO:7), mitochondria biosynthesis gene NrF1 (SEQ ID NO:12) and UCP1 (SEQ ID NO:9) in epididymal white adipose tissue. On the other hand, BGP shows significant increase of expression of PGC1α in gastrocnemius muscle and brown adipose tissue as compared to the control group.

[0047] Because PGC1α (SEQ ID NO:4) can regulate heat generation in brown adipose tissue, mice lack of PGC1α (SEQ ID NO:4) expression will die when exposed at low temperature environment due to low body temperature. On the other hand, increase of PGC1α (SEQ ID NO:4) expression in white adipose tissue can enhance activity of mitochondria and increase expression of UCP1 (SEQ ID NO:9). Therefore, the results demonstrate that BGP group mice have enhanced PGC1α (SEQ ID NO:4) gene expression in muscle cell, enhanced PGC1α (SEQ ID NO:4), NrF1 (SEQ ID NO:12) or tfam (SEQ ID NO:13) gene expression in brown adipose tissue cell, and increased PGC1α (SEQ ID NO:4), NrF1 (SEQ ID NO:12) or tfam (SEQ ID NO:13) in white adipose tissue cell, such that mitochondria biosynthesis in the above tissues also increased. Because of this, the test results of the present invention BGP group mice show higher oxygen consumption in the ingestion phase (dark cycle), CO₂ production, and energy expenditure, i.e., an increase in RQ value.

[0048] Therefore, the mitochondria regulator composition of the present invention can be used as a regulator of mitochondria biosynthesis, or used as an alternative or supplement for control of heat and energy generation. For example, the mitochondria regulator composition of the present invention can be administered an effective amount in treatment of symptoms caused by thermogenin deficiency, the number of mitochondria deficiency, mitochondrial dysfunction, mitochondria malfunction or mitochindria dysregulation; and the mitochondria regulator composition further comprises a pharmaceutical acceptable carrier. In addition, the mitochondria regulator composition of the present invention can be used as a food composition for improvement symptoms of thermogenin deficiency, the number of mitochondria deficiency, mitochondrial dysfunction, mitochondria malfunction or mitochindria dysregulation. The food composition can further contain an additive, wherein the additive can be but not limited to a healthy ingredient, a food ingredient or the combination thereof. The above healthy ingredient can be citric acid, taurine, vitamins, pantothenate, niacin or any other ingredients that may benefit health. The food may be selected from, but not limited to, vegetables, fruits or meats.

Sequence CWU 1

1

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acaaaaacaa acaaacaaaa aaaaacctct cttggtgatg agatgcgctc 2580tctctatctc tctggagtag agaaggcaaa agtgacttcg ctatccaggc agaagggagc 2640tggtcgcctt ggagaacaag agacgagggt gtgatttcat ccagcttctg tttgtaccca 2700gcagaagagc tcacaacact tggttggtct gtggttattg ttgttgttgt tgttattgtt 2760gttgtttcaa agaattaggt ggtaaagtcc cttttcctca gtccctgggg aaagcagtgc 2820tggctacctt caaaagaaac agttgcacaa aggagtctca gacctcatgg actcccggca 2880cccaccctcc aagggggtgg ctacatattt cagagcaggt tgcaccttct acgctcccga 2940cccatcttta gaaaactggc catcttctga cgtcatcatc atttgtgatt aaagaatgat 3000ccagatggac actgccaagg agtcgaggat gtagcccagt ggatggaggg gcttggttcc 3060tggtgccgat ttatggacat ggtggtagat gcctgcaacc ccagcagaag tcagaggtcg 3120ccttcagata cataattaag tgggatgcta gtctgtgccg tgtgagaccc tgtttaaaag 3180agaaaaagat tgctgctgac gaaatgttca aggtcagcat tatgaaaaca ctaataagaa 3240taataataag ggaaaattag cattgggaca tactttaaga tttgcaccct tactgacctt 3300ccccactccc tcctgctctt ccttctcccc tcctccctgt cttctgtcct tcctcaaacc 3360cacttgcccc ctttgtcttc cctccttgct gccaatcaaa ggctctgttg gacagcagtt 3420gctgcaggca gtctgccaag gctcttagga atcagagggc agagcaagtc atcttcatgt 3480atgatcctgg tgagggttga gctcagtcag gaaggagcca gcctttgtgt cacatggcac 3540agccagtcct cagtgcttcc agagggagag ctggtcctat gtttggaagg tcccctagga 3600ggacaggatc ctgttctggt gaatcttaga caaatgccac tcgtaggtga ccttggaaag 3660ggagttttga gtcatgggct ttcgggatag ttgagcattc tgtttgaact cgcctaaaac 3720ttatgaagag tagtcccttg ctgtgtgcct tcagcatgga ccaactgact gacaagttcc 3780gtgtcagtct gcatctgagc tgatgctcag tcgagttcat gcaagtttcg ttctcctgga 3840gcctcgtggg actgccagta agctatccct agagaagcca ggagggacca cagtggcctt 3900ggcttcaaag tcagtgactc tgtgtacatg taccttcctt tatgggaagg atattcacaa 3960tgtggccaca tggtgctagg acctttcagg tcacctagtc agatttctca aggccttagt 4020aacccaagac atgccaggtt aaatactgtg acacacttag gaactgagaa agctggcagc 4080tatgctctgc aaggtgtgtc agtggcatca gccaacagcc caatcagaga tgccaccttg 4140gctcctggag ctctagagca gggttgcaaa gccacttccc agcactgatg gcaaagtctt 4200agtgccagac tccttggaga ccgatgggga ccaggcagcc ttggtgtccc tctgccctgc 4260ctcctgttgt cttcaagagg ctgtgtgacc tagtgaagac acattcgatg tttaagggag 4320ccttaaagat gcacacatgc aaaatttagt catcgactgg actaaggtct atcatggcct 4380cccttttgat cctgtctgcg ggggctcctc cagcccctcc ctccacggca cctctttctg 4440ctggtcctat aggcccttcc ccagaaaaga ttgcttgaag cagaccagaa aaacatggcc 4500cttgggctcc tatacactca gcttgcatct gatcctaaac atgtctcacc ttgagccttt 4560atctaacaca ctatgtcatg ggttatgtta gacactcagc agccagatgc atggaggatg 4620gggacttttg ttctgcatca ttggtttgaa aatgactggc tgaactccag tttaaagttt 4680tcccggtgtc ccctgagatt aaccagcctt tgaccccagg gcctcctaca gccaaaaagc 4740ctgccaccat cactgtatct ctctttaacc tgtgtggcct ttcaagagga gtttccacta 4800gaaaaatcag gaactcccta cagctgctca cccagcatag agagtaggtc ctgttctcct 4860tctacagccc cggggggcgg ggcggggggg tgagaacagg aatctaaacc catcttcaag 4920tagataccac cagcctgatg gccatcttgg cttcctgctg agccaccagg caccactctg 4980tccttggtcc acatttatat ggctgactcc caagaccaga gtaggttaag aatattagag 5040taagagcctg actcaggcca gagatgaccc ttgtctttat ctaaaaacac taaaatctgc 5100atggagaggt tttgatttaa ataagtggac cacgttcctc accgagactc ctctgtgggg 5160ggatgtgtgc tgacatctct ggttttactt cagtggagtg tcctcctggc tcatcaggaa 5220aagatgtatg gtccctaatc aggacagagt gtgagaggct gctgctgcct ggcctgtcac 5280cagcctggga cccctgagga cattttctca acgtcagacc tcagccatct tacttctcag 5340aatcttagtc tgagacatga gaaatggagg ccgttgcttt tctcccaaag gggaacttta 5400gttagggggg gtgggtggtt gaatcgtgag gaacaccttt cagagaatcc tgtgccaacc 5460agaagtggac caaactgcgc ccagggtcag cgtcacgtct tgaccaagca gctggcagca 5520cctgacacct tagtggcgat caagtactac tgttggcaaa aggcaaggag aagcaccgtt 5580ttgtgtcata gcaaccaggc tgtttcgttg tcttttcatg gggtcaaata tgaaaacctt 5640gcagttctat gtagagggag aaataacgct cttctctcac ctctttcccc aacccaaact 5700ccactgcaaa ctcatttatt cggcaaagac aaatgcttca tccctgggtc ccaggtccca 5760ggtggtgagg gcagagcaga ggcaggtggc cctctgggct ccctggttgg cacaaggcac 5820tgggacatct ttcccaggcc cctgggactc agctgtgctt caagtcacac acagagcctg 5880gccctgaaga ccagggagtg attgagtctt tcctggtaaa attgtcactt tgggaaattt 5940cacttaaaaa aaaaaaaaaa aggcggggcc cagccagctc ttttgtcaag cctgaaacta 6000agtgtacctc acaacagacg aacgccactt ggcacccttt ctaggaagat gtcagtatta 6060tccatgttaa gtgtcacgat gttttctgca ctgaatgaaa aagaatgctc ttcatagcta 6120tatcttaata ctgtgatttt taaaacaaaa acaaacaaac aaaccactct gatacaacta 6180gttaactagc ttgtggtcgt gtgtctaatc accgatacct ggagttctct aatccagggt 6240tcagtccagt gtatgttcaa agcctagctc ttgaacctgc tgggcacagc agaagcccaa 6300ataaacaact gcagacagct gccccggggt gtgcacccct cacctgtcac tgtccctaag 6360ctgtgtacaa tctcttccca atgtgtgaat ctgttccttc agtcactttt atttaaaaac 6420aaaaaacaag tgccagccag gtttgactga accatgacag gaaaccgtca actttacatc 6480agtgtttccg tcagggccac tgtgtaggcc tcttaggcta ctgttttaga gaattgttag 6540ctatgaatta ttaccaaaga acggtggcaa tttgagctgt tctgttgagt ctccatgtca 6600tttccaatgt cctggccaca tttctccttg gcgtgtcttc ataactccaa gatccacaat 6660gtcattatca cattggaggc caagggggtg gggtcttaca gacacacctg aggacaggca 6720catttccaaa gcaaggtctg aggcctgctt cctgccactt gctcactact gtccttggtg 6780ccatcctctc agacctgggg atttgcagcc cttcacccct gtgataacag gcctaaatag 6840gaattattga gccgatacca gcatccccac ccccaccccc cagcttgttg tggatacagg 6900gctatccagg acatcaggaa tcagggtgaa cacagaaggg caaatagaat tttctagtca 6960catgagctga ttggttccag gcaattagaa aatggctgta acttaatctt aatttaaaaa 7020aaaaaaaatc gagtctgttt tctccatagg agactgaact gactgtacga gtgatttata 7080tcctgaattt atgggaaccc gtatgtttgg aacgtcctcc tgtaagctga tgaatgtaaa 7140gagttaattt cagggtacag ttttgcctta atggttttaa aaaaaaataa actattttta 7200aaaattaaaa aaaaaa 721621769DNAArtificial sequencePPAR gamma 2caaaacacca gtgtgaatta cagcaaatct ctgttttatg ctgttatggg tgaaactctg 60ggagattctc ctgttgaccc agagcatggt gccttcgctg atgcactgcc tatgagcact 120tcacaagaaa ttaccatggt tgacacagag atgccattct ggcccaccaa cttcggaatc 180agctctgtgg acctctccgt gatggaagac cactcgcatt cctttgacat caagcccttt 240accacagttg atttctccag catttctgct ccacactatg aagacattcc attcacaaga 300gctgacccaa tggttgctga ttacaaatat gacctgaagc tccaagaata ccaaagtgcg 360atcaaagtag aacctgcatc tccaccttat tattctgaaa agacccagct ctacaacagg 420cctcatgaag aaccttctaa ctccctcatg gccattgagt gccgagtctg tggggataaa 480gcatcaggct tccactatgg agttcatgct tgtgaaggat gcaagggttt tttccgaaga 540accatccgat tgaagcttat ttatgatagg tgtgatctta actgccggat ccacaaaaaa 600agtagaaata aatgtcagta ctgtcggttt cagaagtgcc ttgctgtggg gatgtctcac 660aatgccatca ggtttgggcg gatgccacag gccgagaagg agaagctgtt ggcggagatc 720tccagtgata tcgaccagct gaacccagag tctgctgatc tgcgagccct ggcaaagcat 780ttgtatgact catacataaa gtccttcccg ctgaccaaag ccaaggcgag ggcgatcttg 840acaggaaaga caacggacaa atcaccattt gtcatctacg acatgaattc cttaatgatg 900ggagaagata aaatcaagtt caaacatatc acccccctgc aggagcagag caaagaggtg 960gccatccgaa tttttcaagg gtgccagttt cgatccgtag aagccgtgca agagatcaca 1020gagtatgcca aaaatatccc tggtttcatt aaccttgatt tgaatgacca agtgactctg 1080ctcaagtatg gtgtccatga gatcatctac acgatgctgg cctccctgat gaataaagat 1140ggagtcctca tctcagaggg ccaaggattc atgaccaggg agttcctcaa aagcctgcgg 1200aagccctttg gtgactttat ggagcctaag tttgagtttg ctgtgaagtt caatgcactg 1260gaattagatg acagtgactt ggctatattt atagctgtca ttattctcag tggagaccgc 1320ccaggcttgc tgaacgtgaa gcccatcgag gacatccaag acaacctgct gcaggccctg 1380gaactgcagc tcaagctgaa tcacccagag tcctctcagc tgttcgccaa ggtgctccag 1440aagatgacag acctcaggca gatcgtcaca gagcacgtgc agctactgca tgtgatcaag 1500aagacagaga cagacatgag ccttcacccc ctgctccagg agatctacaa ggacttgtat 1560tagcaggaaa gtcccacccg ctgacaacgt gttccttcta ttgattgcac tattattttg 1620agggaaaaaa atctgacacc taagaaattt actgtgaaaa agcatttaaa aacaaaaagt 1680tttagaacat gatctatttt atgcatattg tttataaaga tacatttaca atttactttt 1740aatattaaaa attaccacat tataaaatt 176933238DNAArtificial sequencePPAR delta 3gccgcaggcc gcggcggacc tggggattaa tgggaaaagt tttggcagga gctgggggat 60tctgcggagc ctgcgggacg gcggcagcgg cgcgagaggc ggccgggaca gtgctgtgca 120gcggtgtggg tatgcgcatg ggactcactc agaggctcct gctcactgac agatgaagac 180aaacccacgg taaaggcagt ccatctgcgc tcagacccag atggtggcag agctatgacc 240aggcctgcag gcgccacgcc aagtgggggt cagtcatgga acagccacag gaggagaccc 300ctgaggcccg ggaagaggag aaagaggaag tggccatggg tgacggagcc ccggagctca 360atgggggacc agaacacacg cttccttcca gcagctgtgc agacctctcc cagaattcct 420ccccttcctc cctgctggac cagctgcaga tgggctgtga tggggcctca ggcggcagcc 480tcaacatgga atgtcgggtg tgcggggaca aggcctcggg cttccactac ggggtccacg 540cgtgcgaggg gtgcaagggc ttcttccgcc ggacaatccg catgaagctc gagtatgaga 600agtgcgatcg gatctgcaag atccagaaga agaaccgcaa caagtgtcag tactgccgct 660tccagaagtg cctggcactc ggcatgtcgc acaacgctat ccgctttgga cggatgccgg 720aggccgagaa gaggaagctg gtggcggggc tgactgccag cgaggggtgc cagcacaacc 780cccagctggc cgacctgaag gccttctcta gcacatctac aacgcctacc tgaaaaactt 840caacatgacc aaaaagaagg cccggagcat cctcaccggc aagtccagcc acaacgcacc 900ctttgtcatc cacgacatcg agacactgtg gcaggcagag aagggcctgg tgtggaaaca 960gctggtgaac ggctgccgcc ctacaacgag atcagtgtgc acgtgttcta ccgctgccag 1020tccaccacag tggagacagt ccgagagctc accgagttcg ccaagaacat ccccaacttc 1080agcagcctct tcctcaatga ccaggtgacc ctcctcaagt atggcgtgca cgaggccatc 1140tttgccatgc tggcctccat cgtcaacaaa gacgggctgc tggtggccaa cggcagtggc 1200ttcgtcaccc acgagttctt gcgaagtctc cgcaagccct tcagtgacat cattgagccc 1260aagttcgagt ttgctgtcaa gttcaatgcg ctggagctcg atgacagtga cctggcgctc 1320ttcatcgcgg ccatcattct gtgtggagac cggccaggcc tcatgaatgt gccccaggta 1380gaagccatcc aggacaccat tctgcgggct ctagaattcc atctgcaggt caaccaccct 1440gacagccagt acctcttccc caagctgctg cagaagatgg cagacctgcg gcagctggtc 1500actgagcatg cccagatgat gcagtggcta aagaagacgg agagtgagac cttgctgcac 1560cccctgctcc aggaaatcta caaggacatg tactaaggcc gcagcccagg cctcccctca 1620ggctctgctg ggcccagcca cggactgttc agaggaccag ccacaggcac tggcagtcaa 1680gcagctagag cctactcaca acactccaga cacgtggccc agactcttcc cccaacaccc 1740ccacccccac caaccccccc attcccccaa cccccctccc ccaccccgct ctccccatgg 1800cccgtttcct gtttctcctc agcacctcct gttcttgctg tctccctagc gcccttgctc 1860cccccctttg ccttccttct ctagcatccc cctcctccca gtcctcacat ttgtctgatt 1920cacagcagac agcccgttgg tacgctcacc agcagcctaa aagcagtggg gcctgtgctg 1980gcccagtcct gcctctcctc tctatcccct tcaaagacat gagccatcca aagaaacact 2040acgctctctc tgggcccagc tttccaagaa gcctggcctg gaccaactgc catcccagct 2100tgtggtcacc accacagggt tcctcctcca gagagcaagt gggcagggag cctgggccgg 2160gagccatatt cccaggctgt ctcagcccta ggcacaccac tctctgacac ttcctttctt 2220ctcgccggcg tcctaggtca ttgtcacaga tgacccttgt gctgcctagg agatgacccc 2280tccagatgtc ccctccagat gcggtccaac ggccccactg aagggaaggg ggtagaggca 2340ggccggaagg agcagcggca cacttaggtc ccagggtcag aagctagaca gcgagtgggc 2400aggccctcca tcagcacccc tcctctaccc tgtagcagca tccagactgg cagatcccag 2460taccaggaac tggaccatag ctgttctttc ttctcctggg agatgctggc acacctgccc 2520cccccccccc cttgcagctg ccccggtgta gccatgacac tggctcacct ctcggtcacc 2580acagagtccc tcccattccc tccccaaggc cactggggta cagctatggc cctgttctta 2640ggactggtga tctgtgagca ggcagggata tcctaccagg tcacccctgc cagctcacag 2700gcagagttgc tagggttcct ctgaccctgt cctctctccc actcacttgt accagtagct 2760ctgtggcctt ctcttctttt gcctggctgg tcacctgctc ccatctgctg cttcaagtgg 2820cttgaaactt gctgggtgct cccatactca gccccagccc ggcagatcct gcctctaggc 2880ccataggtga tcagcccagg ctcggctcct gccaacacag aatgctgcca gattccccgc 2940tagcacactc cctgcccctc acctctactg atcaggtctt ggggtgttcc ttgtggggcc 3000cacccaggct gagaatggag ctacatcacc cgccctgccc ccacctgccc agccccgccc 3060aggtctggtg ctgaggatgc agctcctctc agggtctgaa gtctccaaat ctgaaatgta 3120tatttttgct aggagcccca gcttcccgtg tttttaatat aaatagtgta tacagactga 3180cggaacttta aataaatggg aattacgtat ttaagaaaaa aaaaaaaaaa aaaaaaaa 323846464DNAArtificial sequencePGC1 alpha 4gtcatgtgac tggggactgt agtaagacag gtgccttcag ttcactctca gtaaggggct 60ggttgcctgc atgagtgtgt gctgtgtgtc agagtggatt ggagttgaaa aagcttgact 120ggcgtcattc gggagctgga tggcttggga catgtgcagc caagactctg tatggagtga 180catagagtgt gctgctctgg ttggtgagga ccagcctctt tgcccagatc ttcctgaact 240tgacctttct gaacttgatg tgaatgactt ggatacagac agctttctgg gtggattgaa 300gtggtgtagc gaccaatcgg aaatcatatc caaccagtac aacaatgagc ctgcgaacat 360atttgagaag atagatgaag agaatgaggc aaacttgcta gcggttctca cagagacact 420ggacagtctc cccgtggatg aagacggatt gccctcattt gatgcactga cagatggagc 480cgtgaccact gacaacgagg ccagtccttc ctccatgcct gacggcaccc ctccccctca 540ggaggcagaa gagccgtctc tacttaagaa gctcttactg gcaccagcca acactcagct 600cagctacaat gaatgcagcg gtcttagcac tcagaaccat gcagcaaacc acacccacag 660gatcagaaca aaccctgcca ttgttaagac cgagaattca tggagcaata aagcgaagag 720catttgtcaa cagcaaaagc cacaaagacg tccctgctca gagcttctca agtatctgac 780cacaaacgat gaccctcctc acaccaaacc cacagaaaac aggaacagca gcagagacaa 840atgtgcttcg aaaaagaagt cccatacaca accgcagtcg caacatgctc aagccaaacc 900aacaacttta tctcttcctc tgaccccaga gtcaccaaat gaccccaagg gttccccatt 960tgagaacaag actattgagc gaaccttaag tgtggaactc tctggaactg caggcctaac 1020tcctcccaca actcctcctc ataaagccaa ccaagataac cctttcaagg cttcgccaaa 1080gctgaagccc tcttgcaaga ccgtggtgcc accgccaacc aagagggccc ggtacagtga 1140gtgttctggt acccaaggca gccactccac caagaaaggg cccgagcaat ctgagttgta 1200cgcacaactc agcaagtcct cagggctcag ccgaggacac gaggaaagga agactaaacg 1260gcccagtctc cggctgtttg gtgaccatga ctactgtcag tcactcaatt ccaaaacgga 1320tatactcatt aacatatcac aggagctcca agactctaga caactagact tcaaagatgc 1380ctcctgtgac tggcaggggc acatctgttc ttccacagat tcaggccagt gctacctgag 1440agagactttg gaggccagca agcaggtctc tccttgcagc accagaaaac agctccaaga 1500ccaggaaatc cgagcggagc tgaacaagca cttcggtcat ccctgtcaag ctgtgtttga 1560cgacaaatca gacaagacca gtgaactaag ggatggcgac ttcagtaatg aacaattctc 1620caaactacct gtgtttataa attcaggact agccatggat ggcctatttg atgacagtga 1680agatgaaagt gataaactga gctacccttg ggatggcacg cagccctatt cattgttcga 1740tgtgtcgcct tcttgctctt cctttaactc tccgtgtcga gactcagtgt caccaccgaa 1800atccttattt tctcaaagac cccaaaggat gcgctctcgt tcaagatcct tttctcgaca 1860caggtcgtgt tcccgatcac catattccag gtcaagatca aggtccccag gcagtagatc 1920ctcttcaaga tcctgttact actatgaatc aagccactac agacaccgca cacaccgcaa 1980ttctcccttg tatgtgagat cacgttcaag gtcaccctac agccgtaggc ccaggtacga 2040cagctatgaa gcctatgagc acgaaaggct caagagggat gaataccgca aagagcacga 2100gaagcgggag tctgaaaggg ccaaacagag agagaggcag aagcagaaag caattgaaga 2160gcgccgtgtg atttacgttg gtaaaatcag acctgacaca acgcggacag aattgagaga 2220ccgctttgaa gtttttggtg aaattgagga atgcaccgta aatctgcggg atgatggaga 2280cagctatggt ttcatcacct accgttacac ctgtgacgct ttcgctgctc ttgagaatgg 2340atatacttta cgcaggtcga acgaaactga cttcgagctg tacttttgtg gacggaagca 2400atttttcaag tctaactatg cagacctaga taccaactca gacgattttg accctgcttc 2460caccaagagc aagtatgact ctctggattt tgatagttta ctgaaggaag ctcagagaag 2520cttgcgcagg taacgtgttc ccaggctgag gaatgacaga gagatggtca atacctcatg 2580ggacagcgtg tcctttccca agactcttgc aagtcatact

taggaatttc tcctacttta 2640cactctctgt acaaaaataa aacaaaacaa aacaacaata acaacaacaa caacaacaat 2700aacaacaaca accataccag aacaagaaca acggtttaca tgaacacagc tgctgaagag 2760gcaagagaca gaatgataat ccagtaagca cacgtttatt cacgggtgtc agctttgctt 2820tccctggagg ctcttggtga cagtgtgtgt gcgtgtgtgt gtgtgggtgt gcgtgtgtgt 2880atgtgtgtgt gtgtacttgt ttggaaagta catatgtaca catgtgagga cttgggggca 2940cctgaacaga acgaacaagg gcgacccctt caaatggcag catttccatg aagacacact 3000taaaacctac aacttcaaaa tgttcgtatt ctatacaaaa ggaaaataaa taaatataaa 3060ttaaaaggaa agaaaactca caaaccaccc taaaatgaca ctgctgatgc ctgttgtcag 3120cctccggtac cgtcttttca gaaagtgcaa aacccagaaa gtgcaaaacc aacctgcagc 3180aagctctctc tctctcttaa tgtaatcatt acgtgacaat cccgaagaca ctacaggttc 3240catagaactc atatccacct ctctctctct ctctctctct ctctctctct ctctctctct 3300cctctctcct ctctcctctc tccctccctt ctttgccatt gaatctgggt gggagaggat 3360actgcaggca ccagatgcta aactttccta acattttgaa gtttctgtag tttgtccttt 3420gtcctgacac ctatgtatat gttcaaaatg ttgatcttcc actgcagatt ttgaaaagcc 3480ttgttattgg tcaagcgggg agtgtgttca gtggctcctt ctgaggagca gacgcggtgt 3540tacatgagta ctgagagttg agtagaactc tctggatgtg ttcagatagt gtaattgcta 3600cattctctga tgtagttaag tatttacaga tgttaaatgg agtattttta ttttatgtac 3660atactctaca actatgttct tttttgttac agctatgcac tgtaaatgca gccttctttt 3720caaaactgct aaatttttct taatcaagaa tattcaaatg taattatgag gtgaaacaat 3780tattgtacac taacatattt agaagctaaa cttactgctt atatatattt gattgtaaaa 3840aaaaaaaaaa acaaaaccaa caaaacaaaa gacagtgtgt gtgtgtgtgt ccgttgagtg 3900caagtccaac aaaatggcgc ttcacgcaca tccatccctt cttaggtgag cttcaatcta 3960agcatcttgt caacaacaac aaaaatccta ggcccctcaa ggtattaacc acttctgcaa 4020tatttttcca cattttcttg ttgcttgttt ttctttgaag ttttatacac tggatttgtt 4080aggggaatga aattttctca tctaaaattt ttctagacaa tatcatgatt ttatgtaaag 4140tctctcaatg gggaaccatt aagaaatgtt tttattttct ctatcaacag tagatttgaa 4200actagaggtc aaaaaaaatc tttttaaaat gctgttttgt tttaattttt gtgattttaa 4260tttgatacaa aatgctgagg taataattac agtatgattt ttacaatagt caatgtgtgt 4320ctgaagacta tctttgaagc cagtatctct ttcccttggc agagtatgat gatggtattt 4380aatctgtatt ttttacagtt atacatcctg taaaatactg atatttcatt cctttgttta 4440ctaaagagac atatttatca gttgcagata gcctatttat tataaattaa gagatgatga 4500aaataataag gtcagtggag actttctacc cagggtgcat ggcagttgtc aggctggagt 4560gtaccttctt cgtttgggaa actcagctct cgcagaagca gtgttccatc tttcactagc 4620atggcctctg atacgaccat ggtgttgttc ttggtgacat tgcttctgct aaatttaata 4680ttaataataa taaatgtcag aaaaaaaacc ctccattttg agcatcagga tttcatctga 4740gtatggagtc gctgccatgg gagtcactaa actttggagt atgtatttca tttccaaatt 4800gagatgcatt tactgtttgg ctgacatgaa ttttctggaa gatatgatag acctactact 4860taaccgtttt tgtttgtttt tttttctttg ttgttgttgt tttgtttttt gtttttttgt 4920ttttctctct cacccaacac tatcttacaa aatgggtttc acccccaggc caatgcagct 4980aattttgaca gctgcattca tttatcacca gcatattgtg ttctgagtga atccactgtc 5040tgtcctgtcg aatgcttgct caagtgtttg gcttattatt tctaagtaga tagaaagcaa 5100taaataacta tgaaataaaa aagaattgtg ttcacaggtt ctgcgttaca acagtaacac 5160atctttaatc cgcctaattc ttgttctgta ggataaatgc aggtatttta actctttgtg 5220aacgccaaac taaagtttac agtctttctt tctgaatttt gagtatcttc tgttgtagaa 5280taataataaa aagactatta agagcaataa attattttta agaaatcaat atttagtaaa 5340tcctgttatg tgtttaagga ccagatgcgt tctctatttt gcctttaaat ttttgtgatc 5400caactttaaa aacatacgtt gtcttgtttg ccctggatca tggacatgac taaaattttg 5460tggtttcttt tcttacttat caaaagacaa cactacagat ttcatgttga ggattcattg 5520agctctcacc ctctggcctg acaaatcttg ttaccatgaa gatagttttc ctccgtggac 5580ttcaaattgc atctaaaatt agtgaagctt gtgtatctta tgcagacact gtgggtagcc 5640catcaaaata taagctgtaa gctttgttcc tttcattttt ttttttttac ttcttttggg 5700agagaatatt tccaacaaac acatgcaccc caccaacagg ggaggcaaat ttcagcatag 5760atctataaga ctttcagatg accatgggcc attgccttca tgctgtggta agtactacat 5820ctacaatttt ggtacccgaa ctggtgcttt agaaatgcgg ggtttttatt aaaaaaaaaa 5880aaaagaaatg tagcagaata attcttttag tgcagcaact cagtttttgt aaaggactct 5940gagaacactt gggctgtgaa cattcaaagc agcagagagg gaacctggca ctattggggt 6000aaagtgtttg ggtcagttga aaaaaaggaa accttttcat gcctttagat gtgagctaac 6060agtaggtaat gatcatgtgt ccctttttga tggctgtacg aagaacttca atcactgtag 6120tctaagatct gatctataga tgacctagaa tagccatgta atataatgtg atgattctaa 6180atttgtacct atgtgacaga cattttcaat aatgtgaaaa ctgcagattt gatggagcta 6240ctttaagatt tgtaggtgaa agtgtgctac tgttggttga actatgctga agagggaaag 6300tgagtgatta gtttgagccc ttgctggctc ttttccacct gccaattcta catgtattgt 6360tgtggtttta ttcattgtat gaaaattcct gtgatttttt tttaaatgtg cagtacacat 6420cagcctcact gagctaataa agggaaaaga atgtttcaaa tcta 646454331DNAArtificial sequenceCPT1a 5gtcggtgagc ctggcctcgc ccgccccggc ccggactccg ctcgctcatt ccgccgccgc 60cgtctgcaga ctcggtcacc actcaagatg gcagaggctc accaagctgt ggccttccag 120ttcacagtca cccctgatgg catcgatctc cgcctgagcc atgaagccct caaacagatc 180tgcctgtcag ggctgcactc ctggaagaag aagttcatcc gattcaagaa tggcatcatc 240actggtgtgt tccccgcgag tccctccagc tggcttatcg tggtggtggg tgtgatatca 300tccatgcata ccaaagtgga cccctccctg ggcatgattg caaagatcaa tcggacccta 360gacaccactg gccgcatgtc aagccagacg aagaacatcg tgagtggcgt cctctttggc 420acagggctct gggtggcgat catcatgact atgcgctact cgctgaaggt gctgctctcc 480taccatggct ggatgtttgc agagcacggc aaaatgagcc gcagcaccag aatctggatg 540gctatggtca aggtcttctc gggtcgaaag cccatgttgt acagcttcca gacgtctctg 600ccgcgcctgc ctgtcccagc tgtcaaagat accgtgagca ggtacctgga gtctgtgagg 660ccactgatga aggagggaga cttccaacgc atgacagcac tggcccagga ttttgctgtc 720aaccttggac ccaaattgca gtggtatttg aagctaaaat cctggtgggc cacaaattat 780gtgagtgact ggtgggagga atacatctac ctgcggggcc gagggccgat catggttaac 840agcaactact acgccatgga gatgctctac atcaccccaa cccatattca ggcagcgaga 900gctggcaaca ccatccacgc catactgctg tatcgtcgca cggtagaccg tgaggaactc 960aaacctattc gtcttctggg atctacaatt cccctctgct ctgctcagtg ggagcgactc 1020ttcaatactt cccgcatccc tggggaggag acagacacca tccaacacgt caaggacagc 1080aggcacattg tcgtgtacca cagaggccgt tacttcaagg tctggctcta ccatgacggg 1140aggctgctga ggccccgtga gctggagcag cagatgcagc agatcctgga tgacacctca 1200gagccgcagc ccggggaagc caagcttgcc gccctcactg ccgcagacag agtgccctgg 1260gcgaagtgtc ggcagaccta ttttgcacga ggaaaaaata agcaatctct ggatgcggta 1320gaaaaggcag cattcttcgt gacgttggac gaatcggaac agggatatag agaggaggac 1380cctgaggcat ctattgacag ctatgccaaa tctctgctgc atggtagatg tttcgacagg 1440tggtttgaca agtccatcac ctttgttgtc ttcaaaaaca gcaagatagg cataaacgca 1500gagcattcct gggcggacgc gcccatcgtg ggccatctgt gggagtatgt catggccacc 1560gacgtcttcc agctgggcta ctcagaggat ggacactgta aaggagacaa gaaccccaac 1620atccccaaac ccaccaggct acagtgggac attccaggag aatgccagga ggtcatagag 1680acatccctaa gcagtgccag ttttttggca aatgatgtgg acctgcattc cttcccattt 1740gacacctttg gcaaaggctt gatcaagaag tgccggacga gtcccgatgc cttcatccag 1800ctggcactgc agctcgcaca ttacaaggac atgggcaagt tctgcctcac gtatgaggct 1860tccatgactc ggctcttccg agaggggagg acagagactg tacgctcctg cactacggag 1920tcctgcaact ttgtgctggc catgatggac cccacaacaa cggcagagca gaggttcaag 1980ctgttcaaga tagcttgtga aaagcaccag cacctgtacc gcctcgccat gacgggcgct 2040ggcatcgacc gccacctctt ctgcctctat gtggtgtcca agtatctggc agtcgactca 2100cctttcctga aggaggtact gtctgagcca tggaggttgt ccacgagcca gactcctcag 2160cagcaggtgg aactgtttga ctttgagaaa taccctgact atgtgtcctg tggcgggggc 2220tttgggccgg ttgctgatga cggctatggt gtttcctaca ttattgtggg agagaatttc 2280atccacttcc atatttcttc caagttctct agccctgaga cagactcaca ccgctttggg 2340aagcacttga gacaagccat gatggacatt atcaccttgt ttggcctcac cgccaattcc 2400aaaaagtaac tgtcggagcc gcacggaagg aaaatggact ctagtgatac aaaccaaatg 2460aataggtgtt gctcctgacc ataggacagg cagaaaattg ttcttataaa actcagtttt 2520ccttccagaa ggtttaccgt cggtctccct agaacaaccg taggctccac cgtttgactt 2580gtgaccctac tacatccaga gatgccttgg ctccaggaat attgggcaca gtcccccgaa 2640gtcttttgaa tcggctccta atggataaag ggatttaaat gctggtgaat ccctggattt 2700tgggggttgt atcaatatgt gttggaggtg acagacttcc tcagtggtga ccctgtggat 2760acttgggact tgacttcacc caggcagtga gagcatcacc ttgtggaaag agaaagtggc 2820ttcagagcca gtggaggtaa cagctctagc taacacacct gtaacacact aatggaatgg 2880ttaggcctgg ggattaaggt tctgctatga atgacagcca ccatcgcttt gggagtccac 2940atttgactcc acatttcctg gaagcaggat accacctcct cagtgccacc ttcgaaaccc 3000agtgccttaa cgatgggagc ccattggcaa gtggggccat agagaaggct tagcatgtga 3060agcctttggg tggatatgtg agggtgctgc ttcccctcac aagttcctgc atagagatgt 3120ccctaagtaa gcacttcccc caccctagaa gatgaggtcc ctggtggagg gagcgatgca 3180gaatctcatt ggccaccagt tccattaagc aacaaaataa cagatgtgtc cacagaggga 3240agtgaggggc ttggtagtca aaggctacca agttggacac cagctggaga gtgtggcagc 3300cattggcaag gagagtgaga ccctggtcac tgagtcaggc atactgacac aggcagccaa 3360agccttgtca tggcagccag gagatagaga tcctggcaga tacaccaacg ggctcatctt 3420ctaatcccac ccagtcagat tccaaccaga gcaaattcga tagaaggcta ggtcattttg 3480gtgacagact cgggggtctc aagtaatggg tgctttgtac ccaaatacca tccctctgtg 3540agagtgcctt tcttgacaac atccaataga ctgtaaagca actccgtttg gtattccatg 3600taaacatagc ataatggagt ggcctcccct acctgttacc atcctgtcct gacaagttta 3660gctcttcgtg ttttaaatca tgtatttatt ttccagtgcc cctttggcct tgcttgattc 3720ctactcgtgt gctagctgta acagaagtga gggtggggtg gccagaagta cagagaggtg 3780ctggctgaac agctcatgcg tgttttataa gtatccatga atacaaaaaa aagaatcaca 3840cctacaaggg ccaaagtttt tttcctacta aaaacaagaa aacaaaaggc aacataaata 3900tatagcagag acaactgtaa gtcaaagccg cctgaccgcg ctcttaggac tacttgctaa 3960cctctgttac tcggagtatt cctgctagta cccaagtgtg acattcctct ctcaggtctc 4020cagtgtcctt ccttgctgct cctgagcagt taccaatgca attttttact ccttccaagg 4080cagaagagtg ggctttcact gtaagtgttc aaaggaggag gtaagactac tatgtattta 4140atgtggaaca aaacatagtc ttaccgcagc caaggttcga atttggtttt ctaatctgtc 4200cattgcatgt aaataccata tgctgtttgg atataaatct tagaaatgca tgtgtgaacg 4260aatatagctg accattaata aaacattaat cccgcctact aaaaaaaaaa aaaaaaaaaa 4320aaaaaaaaaa a 433162894DNAArtificial sequenceCPT1b 6tgaaggacgt ggggacatgg gccagagagg ccagacccat acaccgacag aagcaaacct 60gagctgtgct gaataaaccc caggatggcg gaagcacacc aggcagtagc tttccagttc 120actgtgaccc cagacggggt cgacttccgg cttagtcggg aggctctgag acacatctac 180ctgtctggaa tcaactcctg gaagaaacgc cttattcgaa tcaagaatgg catccttagg 240ggtgtgtacc ctggcagccc caccagctgg ctggttgttg tcatggcaac agttggttcc 300aactactgca aggtggacat ctccatggga ctggtcgatt gcatccagag atgcctcccg 360gaaaggtatg gccactttgg gaccccacag acagaggcac ttctcagcat ggtcatcttc 420tccaccggag tctgggcgac aggcattttc ttcttccgac aaaccctgaa gctgctgctc 480tcctaccacg ggtggatgtt cgagatgcac agcaagacca gccatgccac caagatctgg 540gctatctgtg tccgtctcct gtccagccgg cggcccatgc tctacagctt ccaaacgtca 600ctgcctaagc ttcctgtccc cagcgtgcca gccacaattc accggtactt ggattctgtg 660cggcccttat tggatgatga agcatattac cgcatggaga cattggccaa ggaattccag 720gacaagactg cccccaggct gcagaaatac ctggtgctca agtcatggtg ggcaactaac 780tatgtgagtg actggtggga agaatatgtc tacctccgaa gcaggagccc cctcatggtg 840aacagcaact attatgccat ggattttgtg cttattaaga acacaaatgt gcaagcagcc 900cgtctaggca atgccgttca cgccatgatc atgtatcgcc gcaaactgga ccgtgaagag 960atcaagccgg tcatggcact gggtatggtg cccatgtgct cctaccagat ggagaggatg 1020ttcaacacta cacgcatccc aggcaaagag acagacttgc tacagcacct ctcagagagc 1080aggcacgtgg ctgtctacca caaaggtcgc ttcttcaagg tctggctcta tgagggctcg 1140cgcctgctca agccccgaga cctggagatg cagttccaga gaatcctcga cgacccttcc 1200ccacctcagc ctggggagga gaagctggca gccctcaccg caggaggaag ggtagagtgg 1260gcagaggcac gtcagacctt cttcagctct ggcaagaaca agatgtctct ggacgccatc 1320gaacgtgctg ctttctttgt gaccctggat gaagattctc attgctacaa ccctgacgat 1380gagaccagtc ttagcctcta cggcaaagcc ttgctccatg gcaactgcta taacaggtgg 1440tttgacaaat ctttcaccct tatctcctgc aagaatggcc tgttaggcct caacaccgaa 1500cactcgtggg cagacgcgcc catcattggg cacctctggg agtttgtcct gggcactgat 1560acctttcacc tgggctacac ggagacagga cactgtgtgg gtgagccaaa caccacgttg 1620ccaccccctc agcggctgcc gtgggacatt cccgagcagt gccgggaagc catcgagaac 1680tcgtaccaag tagccaaggc actggccgat gacgtggagc tctactgctt ccagttctta 1740ccctttggca aaggtcttat caagaagtgt aggaccagcc ccgacgcttt tgtgcagatt 1800gccctacagc tggctcattt ccgggacaaa ggcaagttct gcctgactta cgaggcctcg 1860atgacaagaa tgttccgaga ggggcggact gagactgtgc gttcctgtac caacgagtcc 1920gcagcctttg tgcaggccat gatgaagggg tcccataaga aacaagacct ccaagatctc 1980ttccggaaag cctccgaaaa gcaccaaaac atgtaccgcc tagccatgac aggggctggg 2040atcgaccggc acctcttctg cctttacatc gtctccaagt acttaggagt tagctctcct 2100ttcctggctg aggtactttc tgaaccctgg agcctctcca ccagccagat cccccagttc 2160cagatctgca tgtttgaccc aaaacagtat cccaatcatc tgggtgctgg aggtggcttt 2220ggtcccgtgg cggatgatgg ctacggggtc tcttacatga tcgcaggaga aaacaccatg 2280ttcttccaca tctccagcaa atactcaagt tcagagacga acgcccagcg ctttgggaac 2340cacatccgcc aagcactgtt ggacatcgcc gaacttttca aaatttccaa gacagacagc 2400tgaggaaaag agatacccca gctgccctct ggtccccacc tggtggaaga agaggcctgt 2460ggccagctca caggcataag gggtggcgtg cacacacgcc cagttcggag aacagctctt 2520gaggcagtgc tccccggagg aggcagtgct ccctgggcag atactgctcc tctagggccc 2580ccgctggagg tgggattgga gcagcagggg aattttgatt tttttttttt ttttttggct 2640tggtagatgt taataaaaat aaggctgtat aattcttact tggctgttag gtgcctatgt 2700ttttgttaga gaacgataag gccctttcct gccccagctc agcctaggat ggaggcgatg 2760gaaggggtcg gagaatgttc ataatgggct tcttacctgc tttgaaatgg gtgctcttct 2820tgaataatgc ggacttggag agcgctgtcc aacctctcat gtgcacttgg aataaattct 2880tactttagaa cctt 289471892DNAArtificial sequenceACD1 7gccgccgtcc atcccgccat ggctgcgcgc ctgctcctcc gctccctgcg cgtcctgagc 60gcccgctcgg cgccacgccc gctgccctcc gcccgatgtt ctcattctgg agcagaagcg 120cgtctagaaa ctccttctgc taaaaaatta actgacattg gaatcaggag aatcttttcc 180tcggagcatg acattttccg ggagagtgta aggaagtttt tccaagaaga agtgattcct 240caccacacag aatgggagaa agctggagaa gtgagtagag aggtctggga aaaagctggc 300aagcagggct tgcttggcat caacatcgca gagaaacatg gcggcattgg tggggacttg 360ctctcaacag cagttacttg ggaagagcaa gcgtactcca attgcacagg ccctggcttc 420agcctccact cagatattgt catgccctat attgcgaatt acggcacaaa agaacagatc 480gagaagttca tcccccagat gacggcgggc aagtgtatcg gtgccatagc catgacagag 540cctggggctg gaagtgactt acaaggagta agaacgaacg ccaaaagatc tgggagtgat 600tggattctca atggaagcaa ggtgttcatc actaatggct ggttaagtga tctcgtgatc 660gtcgtggccg tcaccaaccg tgaagctcga tcgcctgccc atggcattag cctctttttg 720gtggaaaacg gaatgaaagg atttatcaag ggccggaagc tgcataagat gggaatgaaa 780gctcaggaca cagcagaact attctttgaa gatgtccgat tgccagctaa tgccttactt 840ggagaagaga ataaaggctt ctactacctc atgcaagagc ttccacagga aaggctctta 900attgctgagt tggcgatttc tgcctgtgag ttcatgtttg aagaaaccag gaactacgtg 960aagcaaagaa aagcttttgg gaaaacagtt gcacacatac agacggtgca gcataaacta 1020gcagaattaa agacacacat atgtgtcacc agagcttttg tggacagctg tctgcagttg 1080catgaaacca aacgtctgga ctccggttct gcttccatgg caaaatactg ggcatctgaa 1140ttacaaaaca gtgtagctta tgaatgtgtg caactccacg gaggctgggg gtacatgtgg 1200gagtacccga ttgcaaaagc ttacgtggat gctcgggtgc agccgatcta cggtggtacc 1260aacgaaataa tgaaagagct gatcgcaaga cagatcgtca gtgacagcta gacatctgcc 1320tacatcctgg aatcctatta catgcagcta atgcggattc taatctactt gagataaagt 1380gtaacctgga aaaggggggg aaatggtaaa gctggtttta tgtatgattg ttacagagaa 1440agaaataaaa tagaattcta aagattaaca cagggagaga gaaatttttg agcccaagag 1500tctaaagttt tgtcatgaaa ggtataacct tttttcatgc atatacagtg aatataaaag 1560attttctaac tgaagagcct tttaatgtct tacttgtctt tcaaattctg aagagcataa 1620gttggctttc attcttaaag ttgaggcaga atttaatatt aataatactt acaagacttt 1680ggaaaggtca aataattgta acttatatga agtcatttca gctacttttt gctccatatt 1740cccccaggac attggttccc accatgttac ccccaacccc atgtttttta aagtaatgaa 1800cagaaccctt cagaaaaaag tggaccgtac tgtatataat gcacatagag gcaattgtgt 1860atcaatatta aaaataaagt aaaacttaaa gc 189283810DNAArtificial sequenceACS1 8ctctttgcat atgcaacgag cgccagcccg gggtgcgcgt ccaggactgc ggctcaacag 60acgctgctca gccggcgccc gggaaacgtc gctgcggttg tggccgcggt cgcgggctcg 120gacgaggagg cggcggcaga gcgggaggct gagccggcag caggcggtcg tccccgtctc 180gcagggcggc cccagcagct gcgtcagggt cctgaggagg tggcgctggg caggagccgc 240tctgaggagc agccaggcct gcgtgggtcg gagcccgcga ttctcattga aatctgttaa 300ttctattttt tgaacactta tgaataacca cgtatcttca acaccatcaa ccatgaagct 360aaaacaaacc atcaacccca tacttttata tttcatacat tttataatat cactctatac 420tattttaaca tacatcccat tttatttttt gtgtgagtca aaacaagaga aaccaaacca 480aattaaagca aaacctgtca gttccaaacc ggactctgca tacagatcta tcaacagtgt 540ggatggcttg gcttcagtgc tgtatcctgg ctgcgataca cttgataaag tctttatgta 600tgcaaaaaac aaatttaaaa acaaaagact attgggaaca cgtgaaattt taaatgagga 660agatgaaata cagccaaatg gaaaaatttt taaaaaggtt attctggggc actataattg 720gctttcctat gaagatgtct tcatccgagc ccttgacttt ggaaatgggt tacaaatgtt 780gggccagaaa ccaaaggcca acatcgccat cttctgtgag accagggctg agtggatgat 840cgctgcacag gcgtgtttta tgtataactt ccagcttgtt acactgtatg ctactctggg 900aggtccagcc attgttcatg gactgaatga gacagaggtg accaacatca ttactagcaa 960agaactcttg caaacaaagc tgaaggatat agtctctttg gtcccacgtc tgcggcatat 1020cattactgtt gatgggaagc ctccaacctg gtctgagttc cccaaaggtg tcattgtaca 1080caccatggct gcagtgcagg ctctaggagt gaaggccaac gtggaaaaga aagctcacag 1140caaaccactg ccctcagata ttgcagtaat catgtacaca agtgggtcca caggaattcc 1200aaagggagtc atgatctcac acagcaacat cattgcttct ataacgggga tggcgagaag 1260gattccaaga ctgggagagg aagatgtgta tattggctac ttgcccctgg cacatgttct 1320agaattaagt gctgagcttg tgtgtctttc tcatggatgc cgaatcggct actcttcacc 1380acagacatta gcagatcagt cttcaaaaat aaaaaaagga agcaaaggag acacatccgt 1440gctgaagcca acactgatgg cagctgttcc ggaaatcatg gatcggatct acaaaaatgt 1500catgaataaa gtgaatgaaa tgagtgcttt tcaacgaaac ttgtttattt tggcatataa 1560ttataagatg gaacagattt caaaagggtg tagtactcca ctgtgtgacc gctttgtttt 1620ccggaatgtc cgaaggctgc tgggtggaaa tattcgcctt ttactgtgtg gtggtgctcc 1680gctttctgca acaacgcagc gattcatgaa tatctgtttc tgctgtcccg ttggtcaggg 1740gtatggactc acagaatcta ctggggctgg aacaattaca gaagtgtggg actacaatac 1800cggcagagtg ggagcaccat tagtttgctg

tgaaatcaaa ttaaagaact gggaggaagg 1860tggctatttt aatactgaca aaccacatcc cagaggtgaa attcttattg gtggccaaaa 1920tgtgacaatg gggtactaca aaaatgaagc aaaaacaaag acagatttct ttgaagatga 1980aaatggacag cggtggctgt gcactggaga tattggagag tttgaccctg acggctgtct 2040gaagatcatt gaccgtaaaa aggaccttgt gaaactacag gcaggagagt acgtttctct 2100cgggaaagta gaggcagctt tgaagaacct cccactgata gataacattt gtgcgtatgc 2160aaacagctac cattcttacg taattgggtt tgttgtgcca aatcaaaagg aacttacaga 2220gctagctaga acaaaaggat ttaaaggaac ttgggaagag ctgtgtaaca gcagcgagat 2280ggaaaatgag gtccttaaag tgctttctga agctgctatt tcagcaagtc tggaaaagtt 2340tgaaattcca ctaaaaatac gtttgagccc tgacccatgg actcccgaaa ctggtctggt 2400gacagatgcc ttcaagttga aacgtaaaga gcttaaaaca cactaccagg cagacattga 2460gcggatgtat ggaagaaaat aattagtttt ggcattggtt tgctacagcg agctcagatc 2520aaataggaaa atacttgaaa tgtatgtctc gggccgaggc aaactccatt cctcatatta 2580aatcccggct gttacttctc actacgtcac catttttaac tgacaggatt agtaaagtat 2640taagacagca aactcgtgtc tgtctgttcc ttcccctgct ccagtttgct tctggcatct 2700gtgactgtgc ttgtcaacag gagacttttt cagaatcgta ctggggaagc agcgatttta 2760cagcctcaag tttttaaaca tgatttatat gttctgtaca gttgttcagt ttgtaacttt 2820ttaaagtttg gatgtataga aggataaata ggaaatataa aaattggtta tttggggggc 2880ttttttactt attgtattta aaaataaaag ggtatcaatg tgaaattatg tacattttaa 2940atgcttatga atcaagtcat tgttgaacaa aagatttgtt gctgtgtaat tattgtcttg 3000tatgcatttg agagaaataa atatactcag acttatgttt taagaaattt cgaatatatg 3060cctgacactg ttgggtttat atacttgctt tttctgttgg ggaaaacagt ttgcttggca 3120ctgcattgaa gtgaaagagc aagtaggggt acataacagt tcactcacag agcagctcac 3180cacagagcag cggtggccat gggtgtggtg gtgggtgagg ggaaccaggg ctctggagtt 3240tcgctcacat cacaaagtac ttgtttagag acatcctagg acagtgttct ctgtgttctc 3300gtatgttgtg tgttggacag ttttgtcctt gttgaaattt aactcttacc tttggagaaa 3360ctttgtaaag gaggggaagt gtgttaatac taggagccga aaatttacca tggttgctgg 3420agagcatttg tgtctgcctg atggcttgcc ttcagaatga ttgtgttaaa atatttttat 3480aaaaatgatt taagtcacgt gtgtatgtgt gcatgcagtg attaaagatg tcagaagggg 3540gcgtctgatc ctctgaaatg agttaaaagc tgtggtgaac caaattctac tttctgtaag 3600actggagcat gctcttaaat gctgagctgt cgttccagca ctctttcaaa ggatttgttt 3660ttctttttta aaaaatagaa tgtaagtaag cttcaatgct tttggaaaga tactaacaat 3720tgtgacttga aatgtcagct taaaaggcag tgtctcacca gtacagtaat ggctgattga 3780acagcaaata aagctggtta gtccgcatca 381091644DNAArtificial sequenceUCP1 9aagtgccggg caatctgggc ttaacgggtc ctccctgccc gagcaagagg aagggacgct 60cacctttgag ctgctccaca gcgccgcctc tgcactggca ctacctagcc caggtggctc 120tgcaggagtc cgaagtcgcg ggtttcgtgc ccgcatcagg caacagtgcc actgttgtct 180tcagggctga gtccttttgt tcttgcactc acgcctctct gccctccaag ccaggatggt 240gaacccgaca acttccgaag tgcaacccac catgggggtc aagatcttct cagccggagt 300ttcagcttgc ctggcagata tcatcacctt cccgctggac actgccaaag tccgccttca 360gatccaaggt gaaggccagg cttccagtac cattaggtat aaaggtgtcc tagggaccat 420caccaccctg gcaaaaacag aaggattgcc gaaactgtac agcggtctgc ctgcgggcat 480tcagaggcaa atcagctttg cctcactcag gattggcctc tacgactcag tccaagagta 540cttctcttca gggagagaaa cacctgcctc tctcggaaac aagatctcag ccggcttaat 600gactggaggt gtggcagtgt tcattgggca gcctacagag gtcgtgaagg tcagaatgca 660agcccagagc catctgcatg ggatcaaacc ccgctacacg gggacctaca atgcttacag 720agttatagcc accacagaaa gcttgtcaac actttggaaa gggacgaccc ctaatctaat 780gagaaatgtc atcatcaatt gtacagagct ggtaacatat gacctcatga agggggccct 840tgtaaacaac aaaatactgg cagatgacgt cccctgccat ttactgtcag ctcttgttgc 900cgggttttgc accacactcc tggcctctcc agtggatgtg gtaaaaacaa gattcatcaa 960ctctctgcca ggacagtacc caagcgtacc aagctgtgcg atgtccatgt acaccaagga 1020aggaccgacg gcctttttca aagggtttgt ggcttctttt ctgcgactcg ggtcctggaa 1080cgtcatcatg tttgtgtgct ttgaacagct gaaaaaagag ctgatgaagt ccagacagac 1140agtggattgt accacataag caacttggag gaagagatac tgaacatcat tgggcttcta 1200tgctgggaga ccacgaataa aaccaaccaa agaaatcaaa tgaacagctc cgttgacttt 1260atttacatta caagatcatt tccagtagag agttttgaaa cctcttttaa ttttttttaa 1320agggaaaact aacacataca catagttttt attcttactg tcttaaagac agaagagcat 1380agcattcact aatattttga gaaaataata cctatataaa gtcctgtatt taactggtct 1440ttggggagag gtgggagtgt atgactgggt ataaagaatt ctgattacag ctcaaactag 1500tgggaaggaa aaattagtcc aaaacccttt acatcgataa acactttaaa aaagaaagct 1560atcaaaaaaa tattgccatt tcatcttatt tattgaccac agttcacagc taatatactc 1620aataaagtat tgctaattcc atct 1644104299DNAArtificial sequenceSREBP1 10agtttccggg gaacttttcc ttaacgtggg cctagtccga agccgggtgg gcgccggcgc 60catggacgag ctggccttcg gtgaggcggc tctggaacag acactggccg agatgtgcga 120actggacaca gcggttttga acgacatcga agacatgctc cagctcatca acaaccaaga 180cagtgacttc ccgggcctgt ttgacgcccc ctatgctggg ggtgagacag gggacacagg 240ccccagcagc ccaggtgcca actctcctga gagcttctct tctgcttctc tggcctcctc 300tctggaagcc ttcctgggag gacccaaggt gacacctgca cccttgtccc ctccaccatc 360ggcacccgct gctttaaaga tgtacccgtc cgtgtccccc ttttcccctg ggcctgggat 420caaagaggag ccagtgccac tcaccatcct acagcctgca gcgccacagc cgtcaccggg 480gaccctcctg cctccgagct tccccgcacc acccgtacag ctcagccctg cgcccgtgct 540gggttactcg agcctgcctt caggcttctc agggaccctt ccaggaaaca ctcagcagcc 600accatctagc ctgccgctgg cccctgcacc aggagtcttg cccacccctg ccctgcacac 660ccaggtccaa agcttggcct cccagcagcc gctgccagcc tcagcagccc ctagaacaaa 720cactgtgacc tcacaggtcc agcaggtccc agttgtactg cagccacact tcatcaaggc 780agactcactg ctgctgacag ctgtgaagac agatgcagga gccaccgtga agactgcagg 840catcagcacc ctggctcctg gcacagccgt gcaggcaggt cccctgcaga ccctggtgag 900tggagggacc atcttggcca cagtaccttt ggttgtggac acagacaaac tgcccatcca 960ccgactcgca gctggcagca aggccctagg ctcagctcag agccgtggtg agaagcgcac 1020agcccacaat gccattgaga agcgctaccg gtcttctatc aatgacaaga ttgtggagct 1080caaagacctg gtggtgggca ctgaagcaaa gctgaataaa tctgctgtct tgcgcaaggc 1140catcgactac atccgcttct tgcagcacag caaccagaag ctcaagcagg agaacctgac 1200cctacgaagt gcacacaaaa gcaaatcact gaaggacctg gtgtcagctt gtggcagtgg 1260aggaggcaca gatgtgtcta tggagggcat gaaacccgaa gtggtggaga cgcttacccc 1320tccaccctca gacgccggct caccctccca gagtagcccc ttgtcttttg gcagcagagc 1380tagcagcagt ggtggtagtg actctgagcc cgacagtcca gcctttgagg atagccaggt 1440caaagcccag cggctgcctt cacacagccg aggcatgctg gaccgctccc gcctggccct 1500gtgtgtactg gcctttctgt gtctgacctg caatcctttg gcctcgcttt tcggctgggg 1560cattctcact ccctctgatg ctacgggtac acaccgtagt tctgggcgca gcatgctgga 1620ggcagagagc agagatggct ctaattggac ccagtggttg ctgccacccc tagtctggct 1680ggccaatgga ctactagtgt tggcctgctt ggctcttctc tttgtctatg gggaacctgt 1740gactaggcca cactctggcc cggctgtaca cttctggaga catcgcaaac aagctgacct 1800ggatttggcc cggggagatt tcccccaggc tgctcaacag ctgtggctgg ccctgcaagc 1860gctgggccgg cccctgccca cctcaaacct ggatctggcc tgcagtctgc tttggaacct 1920catccgccac ctgctccagc gtctctgggt gggccgctgg ctggcaggcc aggccggggg 1980cctgctgagg gaccgtgggc tgaggaagga tgcccgtgcc agtgcccggg atgcggctgt 2040tgtctaccat aagctgcacc agctgcatgc catgggcaag tacacaggag gacatcttgc 2100tgcttctaac ctggcactaa gtgccctcaa cctggctgag tgcgcaggag atgctatctc 2160catggcaaca ctggcagaga tctatgtggc agcggccctg agggtcaaaa ccagcctccc 2220aagagccctg cacttcttga cacgtttctt cctgagcagc gcccgccagg cctgcctagc 2280acagagcggc tcggtgcctc ttgccatgca gtggctctgc caccctgtag gtcaccgttt 2340ctttgtggac ggggactggg ccgtgcacgg tgcccccccg gagagcctgt acagcgtggc 2400tgggaaccca gtggatccgc tggcccaggt gacccggcta ttccgtgaac atctcctaga 2460gcgagcgttg aactgtattg ctcagcccag cccaggggca gctgacggag acagggagtt 2520ctcagatgcc cttggatatc tgcagttgct aaatagctgt tctgatgctg ccggggctcc 2580tgcttgcagt ttctctgtca gctccagcat ggctgccacc actggcccag acccagtggc 2640caagtggtgg gcctcactga cagctgtggt gatccactgg ctgaggcggg atgaagaggc 2700agctgagcgc ttgtacccac tggtagagca tatcccccag gtgctgcagg acactgagag 2760acccctgccc agggcagctc tgtactcctt caaggctgcc cgggctctgc tggaccacag 2820aaaggtggaa tctagcccag ccagcctggc catctgtgag aaggccagtg ggtacctgcg 2880ggacagctta gcctctacac caactggcag ttccattgac aaggccatgc agctgctcct 2940gtgtgatcta cttcttgtgg cccgtaccag tctgtggcag cggcagcagt caccagcttc 3000agtccaggta gctcacggta ccagcaatgg accccaggcc tctgctctgg agctgcgtgg 3060tttccaacat gacctgagca gcctgcggcg gttggcacag agcttccggc ctgctatgag 3120gagggtattc ctacatgagg ccacagctcg gctgatggca ggagcaagtc ctgcccggac 3180acaccagctc ctggatcgca gtctgaggag gagggcaggt tccagtggca aaggaggcac 3240tacagctgag ctggagccac ggcccacatg gcgggagcac accgaggccc tgctgttggc 3300atcctgctat ctgccccctg ccttcctgtc ggctcctggg cagcgaatga gcatgctggc 3360cgaggcggca cgcaccgtag agaagcttgg cgatcaccgg ctactgctgg actgccagca 3420gatgctcctg cgcctgggcg gcggaaccac cgtcacttcc agctagaccc caaagctttc 3480ccttgaggac ctttgtcatt ggctgtggtc ttccagaggg tgagcctgac aagcaatcag 3540gaccatgccg acctctagtg gcagatctgg aaattgcaga ggctgcactg gcccgatggc 3600accctcttgc tctgtaggca ccttagtggc ttttccctag ctgaggctca ccctgggaga 3660cctgtacata gtgtagatcc ggctgggcct ggctccaggg caggcccatg tactactttg 3720acttttgcaa actttatttt cataggttga gaaattttgt acagaatatt aaaaaatgaa 3780attatttata acttcagttt tgtttatctg ggtaggcaga tgtctgcctc agctgattgc 3840tatctttcct ggcttgtcct ttgggaagcc ggacttccca tctgttgtaa ggtgtatttg 3900ctggcttggt gatgctatgt tgagccacct tggccctctg atctcatggc tcataaccct 3960tgaggggcct tgatggtctc agttgttcct ttgccttcca gccctccacc aggtaataac 4020cccgtatatc cagaaacaca cacagttccc tagtcatctc tgtgcaccag cataggcgaa 4080ggatcagggc ccattagtga gtagactggg aaccctgttt gtgtcccccg gccccttccc 4140tctactccca accccttagg gaatctggtc ggcatccaca ggccgcacac ttccaaaaca 4200atcgtggtat ctttattgac tttttttttt ctgaatgcaa tgactgtttt tttttttttt 4260aactcttaag gaaaataaac atcttttaga aacagctcg 4299112245DNAArtificial sequenceGK 11atgctggatg acagagccag gatggaggcc accaagaagg aaaaggtaga gcagatcctg 60gcagagttcc agctgcagga ggaagacctg aagaaggtga tgagccggat gcagaaggag 120atggaccgtg gcctgaagct ggagacccat caggaggcca gtgtaaagat gttgcccacc 180tacgtgcgtt ccaccccaga aggctcagaa gttggagact ttctctcctt agacctggga 240ggaaccaact tcagggtgat gctggtgaaa gtgggggagg gggaggcagg acagtggagc 300gtgaagacga aacaccagat gtattccatc cccgaggacg ccatgacggg cactgcggag 360atgctctttg actacatctc tgagtgcatc tctgacttcc tggacaagca tcagatgaaa 420cacaagaaac tacccctggg cttcaccttc tccttccctg taaggcacga agacatagac 480aagggcatcc tgctcaactg gaccaagggc ttcaaggcct ccggagcaga agggaacaac 540atcgtgggac ttctccgaga tgctatcaag aggagagggg actttgagat ggatgtggtg 600gcaatggtga atgacacggt ggccacaatg atctcctgct actatgaaga ccgccaatgt 660gaggtcggca tgattgtggg caccggctgc aacgcctgct acatggagga gatgcagaat 720gtggagctgg tggaaggcga tgaggggcgc atgtgtgtca acacagagtg gggcgccttc 780gggaactccg gtgagctgga cgagttcctc ctggagtacg accggatggt ggatgagagc 840tcagtgaacc ccggtcagca gctgtacgaa aagatcattg gcggaaagta catgggcgag 900ctggtacgac ttgtgctgct caagctggta gaggagaatc ttctgttcca cggagaggcc 960tcagagcagc tgcgcacacg tggtgctttt gagacccgtt ttgtgtcgca ggtggagagc 1020gactctgggg accgaaggca gatccttaac atcctgagca ctctgggcct tcgaccctct 1080gtcgccgact gcgacattgt gcgccgtgcc tgtgaaagcg tgtccactcg cgccgcccac 1140atgtgctcag caggactagc gggggtcata aatcgcatgc gcgaaagccg cagtgaggac 1200gtgatgcgca tcacggtggg cgtggatggc tccgtgtaca agctgcaccc gagcttcaag 1260gagcggtttc acgccagtgt gcgcaggctg acacccaact gcgaaatcac cttcattgaa 1320tcagaggagg gcagcggcag gggagccgca ctggtctctg cggtggcctg caagaaggct 1380tgcatgctgg gccagtgaaa tccaggcaag gacagggacc tgggttccac ggggactcca 1440caccccacaa atgctcccag tccactaggg caggagacct attctgctgc tacccctgga 1500aaatggggag aggcccctgc aagccaagtc agccagtgag acagccctag ggctctcagc 1560ctggggcaag gggcaagagg atcagcggca ccaaaagcct ttcttgctag aatcaactac 1620agagaaaggt gaagcacact caggtcttgc tctttcagct tctggcctcc cacagctgtg 1680ggtctggcct cccaagggag tgcctcctgg acttgcaatg gcctggcttc cctgggaaca 1740catctccatg gggaggtagc ttcagcagct tggccagacc agacctgggc ccccagaaga 1800gtaagggctg cccagacctg gctgttttct tgcctgtggc tgaagaggct gcaaaaccat 1860gggagaccga ctatctagct acatggaggg gactttccag gccacaaaca ttccagagac 1920agtctccttc atatacctcc acccctgagt ggcttacagt tctgggatga accctcctag 1980gagatgccag aggatagagg cccagagtcc ttgctctagg ggacctgaag gggagcgcct 2040cactctgcac tgttagcagg atggcagctt caacactcac atcagtgatc cgggaagaga 2100agcaagccac ccacagcatc tctccaggaa accacccagg tccctctgtc cctcatccct 2160gtcaggtttc ccagatgcca tgccgccctc tccacaccag cttggaacca tgggggagtt 2220tttaattaaa tatttaaaac tactt 2245123587DNAArtificial sequenceNrF1 12ctcggcggcg gcggcggcgg cagaggcggc agcgctcgcc attgccgctg gtggcaggag 60gctgcgagga gccggcgcgg tcgcagtctc cacggcgcag gcccacggta gcgcagccgc 120tctgaggtcg aatggtatgt ggttcatgta gaccacattt tgtttccctc tcacccattg 180atggacactt gggtagcttc catttttggc tgttgtgaat aatgctgcta tgaacatggg 240tgtgcacaga gctctctgag acgctgcttt cagtccttct ggcagtagat cttcatggag 300gagcacggag tgacccaaac tgaacacatg gctaccatag aagcccatgc agtggcccag 360caagtccagc aggtccatgt agccacgtac actgagcaca gtatgctaag tgctgatgaa 420gactcccctt cctcccccga ggacacttct tatgatgact cggacatcct caactccacg 480gcagctgatg aggtaactgc ccatctggct gctgcaggtc ctgtgggaat ggccgctgct 540gctgctgtgg caacagggaa gaaacggaaa cggcctcatg tgtttgagtc taatccatct 600atccgaaaga gacagcagac acgtttgctt cggaaactca gagccacgtt ggatgagtac 660acgacgcgag tgggacagca agcgattgta ctctgcatct caccctccaa acccaaccct 720gtcttcaagg tgtttggcgc agcacctttg gagaatgtgg tgcgaaagta caagagcatg 780atcctggaag acctcgagtc tgctctggca gaacacgccc ctgcgccaca ggaggttaat 840tcagagctgc cgcctctcac catcgatggg attccagtct ctgtggacaa aatgacccag 900gctcagcttc gggcatttat cccagagatg ctcaagtatt ccacaggtcg ggggaaacca 960ggctggggga aagaaagctg caagcctatc tggtggccag aagatatccc atgggccaat 1020gtccgcagtg atgtccgcac agaagagcaa aaacaaaggg tttcatggac ccaggcatta 1080cggaccatag ttaaaaattg ctataagcaa catgggcggg aggatctttt atatgctttt 1140gaagatcagc aaacacaaac tcaggccacc accacacaca gtatagctca tctcgtacca 1200tcacagaccg tagtacagac cttcagcaac cctgatggca ccgtgtcgct catccaggtt 1260ggtacagggg caacagtagc cacattggct gatgcttcag aactgccaac cacagtcact 1320gttgcccaag tgaattactc tgctgtggct gatggagagg tggaacaaaa ctgggccacg 1380ttacagggcg gtgaaatgac catccagacg acgcaagcat cagaggccac ccaggcggta 1440gcatcactgg cagaagccgc agtggcagct tctcaggaga tgcagcaggg agccactgtc 1500accatggccc tcaacagtga agctgccgcc catgctgtcg ccactctggc ggaagccacc 1560ttacaaggtg ggggacagat agtcctgtct ggggaaaccg cagcagccgt cggagcactt 1620actggagtcc aagatgctaa tggcctggtc cagatccctg tgagcatgta ccagactgtg 1680gtaaccagcc tcgcccaggg caacgggccg gtgcaggtgg ccatggcccc agtgaccacc 1740aggatatcgg acagcgcagt caccatggat ggccaggctg tggaggtggt gaccttggaa 1800cagtagcatg gagctctatc atggcagcgt tttctagtct actgcagaat tttttacatg 1860tttgcagagg tgcaatcaaa tggaattaag tctctcgact tggaaagaaa gttttggtaa 1920ccttttttta agaaggaaga aaggcagcag attttggaat cacacttttt taaagcacca 1980ctctgggatc tggtggaatg aacgccaccg atttcactgt cccaaaaagc caaattgtgg 2040ccagacttct ttgtgcagaa atgtgtgtat acttacgtgt gtgtacgtgt gagtgtgaat 2100atatgtatat gtgtacatat ggacatacac atttacatat atgtataaag tatatatgta 2160catacataca tatgtatgaa acctgcatgg aattacctgt atgaaatcaa ggtgaactgt 2220gggaacaaga acccacccag attcgtgggt ggtagggtac atgaccaaac acagtcacct 2280ggttttcgtt cataccaggg tcatgcattg agctactgac agactcaggc ggaggtgacc 2340acgtccttca ccaaagctgc ctcccagtgg ccgcctagac ctctgctaga ttcaccgaag 2400gaaggaagat ccaggacaca gcgtggtcca gagagtgctt gtgaagtcca gggacagaga 2460gtgcgtgcgc acatgtgcgc tttgccagca gagacacacg gcagctggcc caggtgctga 2520ccttgccaca ggcaggtaaa cgccctgcag gctcctggca ggggcaagaa atcgttcctc 2580agcctccatc ttctcccttc ccaggaaccc tcagtctcac gactattcaa gagttgcttg 2640gttgtaaggt cagtcctgtt acaaactgaa ggtgacagaa gtgttaaggg tctgaggagt 2700gttcatggag caggcgggtg taagtgcagg gtgtgtgtgt gtgtgtgtgt gtgtgtgtat 2760gagtaatgga gaaaatggga agattatagg agagcaaaat aggaaggagg gagaaaactc 2820ttcataaatc agggtgcgcc gtgggaaccg tgttctccag ctgtctgcag ctgtatttca 2880gcagaggaga ctgcctcaca caggacctct gcgcaaaggc tggccgtcac agatgtgtca 2940gaagactctg tgaggacttt tcccaggcac atcctggcgg cacaggcctg ggacagcttt 3000cctgctcaca gtgtggcttg cactgagcag tcattgtcac tgtgagcttc tgtgctttcc 3060agccacaagc cctgagtctc ccgtggctca ttcatctgat gtcttgacaa gccaaatctc 3120cactcctggc gtgcagggac tcttcctcct tcctgccagc cctctcccgt gcgtgatagt 3180gtatttaatg tggtgttttt ggttttttgt tttttaatga gacattaaaa gattcttcat 3240gtcttgctca gcctttgaga aaagtttcca attcttatat ttgcttgttt tatataaaac 3300tattcaatgt tctttgtatg ttcttttctg tatgtgataa gggaggggtg ggaaatttgc 3360atatcaatgt cctggttcta caattggtta cttttttttt ttttttaaac tgtgaagctg 3420tccaggggct ttaaggcccg tgttcctttg tggtgaaata agcctcccga tagtttgaga 3480aattgccaag aagataaaag caagatccca gcagcagagc atggaatctg tgttgttctc 3540cattctgtct aaactgcctc attcaataaa tagtttaatg tggcgac 3587133918DNAArtificial sequencetfam 13aacaagcccc cggagttccc acgctggtag tgtggcagtc cataggcacc gtattgcgtg 60agacgaaccg gacggcgccg ggccatcatt cgtcggcccg agcgatggcg ctgttccggg 120gaatgtggag cgtgctaaaa gcactggggc gcacgggggt cgagatgtgc gcgggctgcg 180ggggtcgcat cccctcgtct atcagtcttg tctgtattcc gaagtgtttt tccagcatgg 240gtagctatcc aaagaaacct atgagttcat accttcgatt ttccacagaa cagctaccca 300aatttaaagc taaacaccca gatgcaaaac tttcagaatt ggttaggaaa attgcagccc 360tgtggaggga gctaccagaa gcagaaaaaa aggtttatga agctgatttt aaagctgagt 420ggaaagcata caaagaagct gtgagcaagt ataaagagca gctaactcca agtcagctga 480tgggtatgga gaaggaggcc cggcagagac ggttaaaaaa gaaagcactg gtaaagagaa 540gagaattaat tttgcttgga aaaccaaaaa gacctcgttc agcatataac atttatgtat 600ctgaaagctt ccaggaggca aaggatgatt cggctcaggg aaaattgaag cttgtaaatg 660aggcttggaa aaatctgtct cctgaggaaa agcaggcata tattcagctt gctaaagatg 720ataggattcg ttacgacaat gaaatgaagt cttgggaaga gcagatggct gaagttggac 780gaagtgatct catccgtcga agtgtgaaac gatccggaga catctctgag cattaagatg 840gaagacggag ttgtcattgg gattaggccc aagaaaccag ttaggtctca aagccttaaa 900gtgtcaaact agaacggata aaggtggtta acctttgaca ttcagatcat ttttctgtag 960ccatggactt tctgttaata ctttgagcct tgacagaaga tgatgctgag ttctgccttt

1020tgcttaagaa ctggaacgga gactgtccat gcatctgcat gcagtggtga atcattctgc 1080atttgatggg ctagatagac tgtgaagtga ctttcacact ggtgacagtt gtgtggtggt 1140tttgtgatgt ttttacactg atgaccgtta catatgggtg tggcccttgg gtcccaggcc 1200ggacctgctc tcccagctgt ggcagagctg tggataactg cattttcaaa gaagctgcca 1260ggctttccta gatgaaatga ttcctagaca taaatcatgt gtaagttgat gtttgtatat 1320aataagcgat tgctgatgtc ctgatagcat tttatagtag taacagagag atttacacat 1380ctttctcaaa ttaagaaatt atgtaccaag tctatgcata ggtttttctt gcatagaata 1440aaaactctaa ttttccaaac atgtttctga aattatgtat tttaagatga accatttggt 1500taacagattt tttttttttc aattttaggt agggacttta gaaattactt ttcatttgag 1560agtattcata gagcttgtgt ggtataaatt tttaaatgag aaaatgtgaa aaacaagtct 1620gcaaagtcag aaatctgaaa gcttatccat gacagctaaa ggcctatgca ggagaaagcc 1680aactgtggtg agccagccag gtccagctca ctaactgctc ttcagggcct actcatcaag 1740aaatggattt atgttctaaa taggttttta aaaaggaaag tatcagtgtg aaaattaata 1800tgatctttag tgtttgtgaa tagaatttct tggaacacag ccacatgctt tcttgggttt 1860gttgtgtgtg ggtgctctgt gctccagaga ctacactggg aaaccacagc atacagggat 1920ggcccttcgc agacagtttg ccaccatggt gtctcacggc cactggccat gcaaggcttt 1980tcctcagatg tccttgatgt ttctgtgata ttgtcaccct atcttggggt catcactggg 2040tccctataag cctaactgtt ctctgtgtta gcaaggaaaa tattctttaa cctggaatcc 2100tggtgtagca cagtacagaa gaccactgtg tggagcgaga ccctcctaat ctttactgtt 2160gcacaggaaa aagtgtcttc cccactttga gctggcaaat cccataagcc cttagagaac 2220tcatggcttc aaccaccaca ccactgagca gatctctgag acacaggaca acagagttca 2280tactcatgta tgttttgtat tgaggaggct tagagattgt acattttggg aaagtaagtt 2340tgcagtcact gaacttgaca aggtaggaac agaagaacgc atggaggaga gatgtaagag 2400ttatatatgt aaaacagggt atttgagctg ggtagaaaac ttgcctagaa tgtacaaggc 2460cttggatcca aatcccagaa ctgcaactct ccccagaaga gataatcaga attttagaga 2520tgaatttaag aaaatataat ttttcccgtg gattggaatt ctgggttgtt ggatggcatg 2580ggtttaagcc atagtttgaa ggtggtggaa ggaggccagt gtgaaccagt gcagtctgtc 2640tttccaaagt gcaaatccag gagagacgtg agctctacac gcccctggtt tctggaaagg 2700aactaactcc aagctgtcct tagaatggag aaaatggtga ctcagagaat tgaccatgtg 2760cttcagagca actcaggagc agcaggcact acagcgatac agggatgccc ggacctctaa 2820gatgtaacta cttagctcct agctttccag gcaccctgca gagtgttcaa ggactcggag 2880ctcagtctgg gaagggaatg ggaaaggtag aggcctgggc ggaagccttc tcatggtact 2940tggttcagtt tggttttcct tgtttgtaaa acaagcttac tgataacatt gtaatctgct 3000ttccatgtcc tgttttctaa cgacagagtc tcttttaagc aaaagcagtt gccagaggat 3060cggggaggtg ttgggaggag ctgaaggcat gcggtgaagc tgcacaagct gacaagggct 3120cagtgctgtt tctacttatt gtcatgtaac tgcaattggg ctgccctgtt ttccagtatc 3180cttaaaaaca acaaacccta gttggtctaa gtgtgaacct ctgaatttaa agctggtgtt 3240agcatacgga tgtacagtag ctagaaagcc ttcctgggtt cacccgcacg cactggacca 3300ccagggggcg ctgaaaccac agctttaatg cagacggagc catagtgccc atcagttctg 3360tttggccata ttataagaat tttcttcctc tgatagcaac cctcctttct cccaggtttt 3420gtttatttgt ttttgtttgt ttgtttgttt gtttgtttgt ttttcgagac agggtttctc 3480tgcgttgccc tgcctgtcct gtaactcact ttgtagacca gctggctgta gactcggaga 3540cctacctcag attaagtgct gagattaaga gcttgcctca ccaccaccat caggcttcct 3600ccctcctctt ccgaatttgc caccagcctg tcactgacaa gtttgcaaat gctaaaacag 3660tgcctgtatg ttttgaagtg taaagaacat atttcttttt ttgtaattga gcttaagaga 3720taaaatgaat gtattactca tttgtaaaac ttcctaagca aaaggtaaaa ttatgcacaa 3780ctggtaacca tcaattgttt atcattcaca aatcaaatat tttcgttatt taaccactga 3840tagtaattca ttataaaacc attcttttgc acagttagga atgctgacca agaaactgca 3900ttatttaaat taaatgct 3918

Claims

1. A composition for the regulation of mitochondria biosynthesis consisting essentially of therapeutically effective amounts of whole bitter gourd fruit extract, corn starch and cellulose.

2-15. (canceled)

Images