藏汉民族及3个不同地域的藏族群体线粒体基因组的比较研究：探查自然选择在基因组的印记
|
摘要
在人类漫长的进化历程(evolutionary process),自然选择究竟在人类基因组留下怎样的痕迹,是我们今天一直想解开的秘密。自达尔文的进化论学说问世以来,人类对自己朦胧的过去一直怀有强烈的好奇心和探索的欲望。但由于知识和技术瓶颈的限制,人类了解和探索自身奥秘的愿望一直没能实现。随着人类基因组计划(HGP)、国际单体型图计划(HapMap)的完成和基因组测序技术的日趋成熟,为人类探索自身的研究提供了大量的知识积累和技术平台的支撑,使人类进化历史的研究以新的起点重新提到科学研究的议事日程,使在基因组水平上探索自然选择作用的研究不断涌现。但由于核基因组易发生重组,破坏自然选择的效应,因此使结果的分析和解释变得复杂起来。另外,在研究人类的进化历史时遇到的另一个难题是难于区分自然选择和人口学(demography)事件,例如种群扩散(population expansion)、瓶颈效应(population bottlenecks)、群体结构(population structure)等因素所产生的效应。所以,关于自然选择对人类基因组变异的影响,依然众说纷纭,莫衷一是。mtDNA是独立于核基因组以外的遗传物质,具有较高的拷贝数、缺乏重组、较高的突变率和母系(单亲)遗传等特点。例如缺乏重组意味着有利的突变体由于“搭载效应”(genetic hitchhiking)而使其频率增加,并迅速地在该群体得到富集:母系遗传可促使有利的突变迅速地形成分离、表达,上述特性有利于一些重要的生物学特征如选择的效应等较易被检测。所以,mtDNA是研究人类起源和进化、具有巨大潜力的研究工具。
以往的研究显示mtDNA具有严格的区域(地区)变异的特性,传统的观点将其归因于遗传漂变(genetic drift),自然选择对形成特征性mtDNA变异的作用一直没有得到证明。本研究旨在通过藏汉民族及不同地域的藏族群体mtDNA全序列的比较研究,探查是否存在线粒体基因组存在自然选择、存在何种选择及构成选择的因素。
在本研究中,我们选择40例世居在西藏的藏族群体为研究对象,并以50例汉族群体为对照,对其mtDNA进行全序列测定;对3个不同地域藏族群体线粒体基因组的ATP6、ATP8和Cyt b基因约2kb的区域进行测序研究。应用AppliedBiosystems 3730 DNA自动测序仪对mtDNA进行双向序列测定;采用phredPhrap16.0,Network,DnaSP 4.20.2和SPSS 15.0等软件对基因组数据进行分析。应用SSPro和SSPro8软件对蛋白质的二级结构进行预测;PDB格式的alpha碳原子坐标通过3Dpro计算获得,进一步通过MaxSprout补全其它原子的坐标;利用Rasmol和Swiss-pdbviewer显示并比较结构。单点突变引起蛋白稳定性的改变通过Cheng等开发的基于SVM算法进行预测。利用RNAfold软件包对变异引起的RNA结构改变进行模拟分析。
研究发现,90例藏汉群体属Macrohaplogroup M和N,归类到13个Haplogroups,除M9以外,其它Haplogroup在两个种族之间没有显著性差异。主成份分析显示,第一(PC1)和第二主成份(PC2)分别占总变异的41.3%和10.7%,2个主成份对总变异的贡献率占52.0%。进一步的分析显示,在主成份图上,藏汉群体分别位于不同的象限,第一和第二主成份分别占77.1%和10.1%,2个主成份对总变异的贡献率占87.2%,表现出鲜明的地域特点。藏汉群体mtDNA全序列比对分析发现18个显著性差异的变异位点,其中5个位点是我们首次报道(http://www.mitomap.org),有8个位点变异后被定义在Internal branch。我们对藏族群体中占优势的7个突变所致结构的变化进行结构预测和分析,发现突变后ND2 G4491A,CO2 G7697A,tRNA alanine T5628C和12S rRNA A1041G的结构发生显著变化,其稳定性增加,在能量学上意味着是一种适应性选择。另外,对5个D-loop区突变进行了单体型构建和分析,发现16145位点倾向于和16255、16284组合,16234倾向于和16316组合。我们对40例藏族、50例汉族、144例南亚和48例东亚群体的13个蛋白编码基因进行非同义(nonsynonymous/N)和同义替换(synonymous/S)分析并比较它们之间的差异,发现在40例藏族群体中,ATP6,ATP8和Cyt b基因的N/S比值较大(均大于1),并且Cyt b基因在藏族和南亚群体之间N/S有显著性的差异。
另外,我们对3个不同地域藏族群体线粒体基因组的ATP6、ATP8和Cyt b基因约2kb区域的进行测序研究;应用Taijma's D检验、Fu和Li's D与F检验3种方法进行中性检验,发现随着海拔的增加,3个基因的全序列、ATP6和ATP8基因逐渐偏离中性模式,在ATP6基因出现显著性差异。通过N/S选择分析发现,在西藏群体ATP6基因可能存在适应性选择,并且随着海拔的增高呈现出适应性选择增强的趋势;Cyt b基因则受到纯化选择,并且随着海拔的降低,纯化选择的作用逐渐增大。
通过对藏汉群体mtDNA全序列和不同地域的藏族群体的ATP6、ATP8和Cyt b基因约2kb区域的测序研究,提示在西藏群体ATP6,ATP8,ND2(G4491A),CO2(G7697A),tRNA alanine(T5628C)和12S rRNA(A1041G)基因可能存在适应性选择。其选择的主要因素应该是该群体所处的特殊的地理环境(如高海拔、高寒、低氧等),即不同的地理环境有直接的选择作用。
During the long period of human evolutionary process,it currently leaves a puzzle for what signature of natural selection casts in human genome.Since the appearance of Darwin's Evolution Theory,the intense curiosity and exploring desire possess human beings for their ambiguous past.The limitations underlying knowledge and technique hamper the process of exploring human's mystery.The competition of Human Genome Project and HapMap as well as the maturity of biotechnology in sequencing put the investigation of human evolution from a brand-new standpoint on the agenda.The analysis and explanation on most results of these studies regarding natural selection,however,remain complexity,mainly due to high recombination rate of nuclear genome which can destroy the effects of natural selection.In addition, another puzzle encountered in the investigation of human evolutionary history is to distinguish natural selection from demography,such as the effects of population expansion,population bottlenecks,population structures and so on.Forasmuch, results of most of these studies regarding natural selection remain controversial,with no consensus on their implications.Human mitochondrial DNA(mtDNA),the extra-nuclear genetic material,is characterized by high copy numbers,lack of recombination,high mutation rate and inheritance through purely maternal lines.For example,maternal inheritance can enhance the rapid segregation,expression and adaptive selection of beneficial mtDNA mutation;lack of recombination means that the beneficial mutation can accumulated with the genetic hitchhiking of mtDNA haplotype.Therefore,all these characteristics of mtDNA offer the potentials of investigating human origin and evolution.
Previous studies indicated that mtDNA sequences bore strong geographic variation, which was traditionally attributed to the hypothesis of genetic drift.However,the effect of selection on characteristic variation in mtDNA has not yet been proved.The aim in this study by compared between Tibetan and Han populations,and Tibetans in different zones is to detect the signature for natural selection in mitochondrial genome, meaning which and what are the factors for natural selection.
In this study,we focused on 40 Tibetans who generationally resided in Tibet and 50 Han Chinese from Beijing to thoroughly decipher and compare the mtDNA whole sequences between the two populations and the mtDNA sequences(～2 kb) of ATP6, ATP8 and Cyt b genes between the three zone Tibetans.The mtDNA sequences were performed using Applied Biosystems 3730 DNA sequencer.Data in mtDNA were analyzed using softwares phredPhrap 16.0,Network,DnaSP 4.20.2 and SPSS 15.0. The SSPro and SSPro8 softwares were used to predict the protein secondary structure; the 3Dpro software was used to calculate the alpha carbon atom coordinate in PDB format,further the MaxSprout was used to fill the coordinates of other atoms,and finally Rasmol and Swiss-pdbviewer softwares were adopted to compare the structure. The protein stability variation caused by single-locus mutation was predicted by aid of SVM algorithm which was developed by Cheng et al.The structure changes of RNA conferred by mutation were simulated using the RNAfold software.
Our results showed that all the pooled 90 studied subjects pertained to the Macrohaplogroup M and N,and were classified into 13 haplogroups.No differences were observed among all haplogroups between the two populations except for M9 haplogroup.Principal component analysis indicated that the first and second principal components(PC1 and PC2) respectively accounted for 41.3%and 10.7%of the total variance with the added contribution of 52.0%.Further analysis indicated that the Tibetan and Han populations pitched different quadrants,and PC1 and PC2 respectively accounted for 77.1%and 10.1%of the total variance with a total contribution of 87.2%,suggesting obvious geographic differences.
A total of 18 variants were detected by comparing the mtDNA whole sequences between Tibetan and Han populations;of those 5 variants were reported firstly in current study(http://www.mitomap.org) and 8 variants were defined at the internal branch.After predicting the structure changes conferred by the 7 dominated variants in Tibetans,we found that the structures of ND2 G4491A,CO2 G7697A,tRNA alanine T5628C and 12S rRNA A1041G changed significantly after mutation and the stability was increased,meaning the existence of adaptive selection in bioenergetics. Additionally,we constructed the haplotypes of 5 variants harboring D-loop region, and founded that 16145 locus preferred to be combined with the 16255 and 16284 loci, as well as 16234 with 16316.After comparing the replacement of nonsynonumous(N) versus synonymous(S) of 13 peptide-encoded genes among 40 Tibetans,50 Han subjects,144 south Asians and 48 east Asians,we found that the N/S values of the ATP6,ATP8,and Cyt b genes were relatively large(greater than 1) among Tibetans. Significant difference was found for Cyt b gene between Tibetans and south Asians.
In addition,we compared the sequences(～2 kb) of three ATP6,ATP8 and Cyt b genes among Tibetans in three different zones and found that the D or F value was negative using Tajima's D test,Fu and Li's D test and F test,which significant difference was found for ATP6 gene by Fu and Li's F test.We further performed N/S (nonsynonymous(N) versus synonymous(S)) substitutions analysis for these three zones and it provides evidence for the existence of adaptive selection in ATP6 gene and the adaptive selection trend was increased with the increase of altitudes,whereas for the existence of purifying selection in Cyt b gene and the purifying selection trend was increased with the decrease of altitudes.
The analyses of the mtDNA whole sequences and sequences(～2 kb) of three ATP6, ATP8 and Cyt b genes provide clues for the existence of adaptive selection for ATP6, ATP8,ND2(G4491A),CO2(G7697A),tRNA alanine(T5628c) and 12S rRNA (A1041G) genes in Tibetans.The primary factor of natural selection should be the special geographical environment(e.g.,high-altitude,hypoxia,extreme cold) which this Tibetan locates,namely the different geographical environment has the direct selective action on variation of mtDNA.
以往的研究显示mtDNA具有严格的区域(地区)变异的特性,传统的观点将其归因于遗传漂变(genetic drift),自然选择对形成特征性mtDNA变异的作用一直没有得到证明。本研究旨在通过藏汉民族及不同地域的藏族群体mtDNA全序列的比较研究,探查是否存在线粒体基因组存在自然选择、存在何种选择及构成选择的因素。
在本研究中,我们选择40例世居在西藏的藏族群体为研究对象,并以50例汉族群体为对照,对其mtDNA进行全序列测定;对3个不同地域藏族群体线粒体基因组的ATP6、ATP8和Cyt b基因约2kb的区域进行测序研究。应用AppliedBiosystems 3730 DNA自动测序仪对mtDNA进行双向序列测定;采用phredPhrap16.0,Network,DnaSP 4.20.2和SPSS 15.0等软件对基因组数据进行分析。应用SSPro和SSPro8软件对蛋白质的二级结构进行预测;PDB格式的alpha碳原子坐标通过3Dpro计算获得,进一步通过MaxSprout补全其它原子的坐标;利用Rasmol和Swiss-pdbviewer显示并比较结构。单点突变引起蛋白稳定性的改变通过Cheng等开发的基于SVM算法进行预测。利用RNAfold软件包对变异引起的RNA结构改变进行模拟分析。
研究发现,90例藏汉群体属Macrohaplogroup M和N,归类到13个Haplogroups,除M9以外,其它Haplogroup在两个种族之间没有显著性差异。主成份分析显示,第一(PC1)和第二主成份(PC2)分别占总变异的41.3%和10.7%,2个主成份对总变异的贡献率占52.0%。进一步的分析显示,在主成份图上,藏汉群体分别位于不同的象限,第一和第二主成份分别占77.1%和10.1%,2个主成份对总变异的贡献率占87.2%,表现出鲜明的地域特点。藏汉群体mtDNA全序列比对分析发现18个显著性差异的变异位点,其中5个位点是我们首次报道(http://www.mitomap.org),有8个位点变异后被定义在Internal branch。我们对藏族群体中占优势的7个突变所致结构的变化进行结构预测和分析,发现突变后ND2 G4491A,CO2 G7697A,tRNA alanine T5628C和12S rRNA A1041G的结构发生显著变化,其稳定性增加,在能量学上意味着是一种适应性选择。另外,对5个D-loop区突变进行了单体型构建和分析,发现16145位点倾向于和16255、16284组合,16234倾向于和16316组合。我们对40例藏族、50例汉族、144例南亚和48例东亚群体的13个蛋白编码基因进行非同义(nonsynonymous/N)和同义替换(synonymous/S)分析并比较它们之间的差异,发现在40例藏族群体中,ATP6,ATP8和Cyt b基因的N/S比值较大(均大于1),并且Cyt b基因在藏族和南亚群体之间N/S有显著性的差异。
另外,我们对3个不同地域藏族群体线粒体基因组的ATP6、ATP8和Cyt b基因约2kb区域的进行测序研究;应用Taijma's D检验、Fu和Li's D与F检验3种方法进行中性检验,发现随着海拔的增加,3个基因的全序列、ATP6和ATP8基因逐渐偏离中性模式,在ATP6基因出现显著性差异。通过N/S选择分析发现,在西藏群体ATP6基因可能存在适应性选择,并且随着海拔的增高呈现出适应性选择增强的趋势;Cyt b基因则受到纯化选择,并且随着海拔的降低,纯化选择的作用逐渐增大。
通过对藏汉群体mtDNA全序列和不同地域的藏族群体的ATP6、ATP8和Cyt b基因约2kb区域的测序研究,提示在西藏群体ATP6,ATP8,ND2(G4491A),CO2(G7697A),tRNA alanine(T5628C)和12S rRNA(A1041G)基因可能存在适应性选择。其选择的主要因素应该是该群体所处的特殊的地理环境(如高海拔、高寒、低氧等),即不同的地理环境有直接的选择作用。
During the long period of human evolutionary process,it currently leaves a puzzle for what signature of natural selection casts in human genome.Since the appearance of Darwin's Evolution Theory,the intense curiosity and exploring desire possess human beings for their ambiguous past.The limitations underlying knowledge and technique hamper the process of exploring human's mystery.The competition of Human Genome Project and HapMap as well as the maturity of biotechnology in sequencing put the investigation of human evolution from a brand-new standpoint on the agenda.The analysis and explanation on most results of these studies regarding natural selection,however,remain complexity,mainly due to high recombination rate of nuclear genome which can destroy the effects of natural selection.In addition, another puzzle encountered in the investigation of human evolutionary history is to distinguish natural selection from demography,such as the effects of population expansion,population bottlenecks,population structures and so on.Forasmuch, results of most of these studies regarding natural selection remain controversial,with no consensus on their implications.Human mitochondrial DNA(mtDNA),the extra-nuclear genetic material,is characterized by high copy numbers,lack of recombination,high mutation rate and inheritance through purely maternal lines.For example,maternal inheritance can enhance the rapid segregation,expression and adaptive selection of beneficial mtDNA mutation;lack of recombination means that the beneficial mutation can accumulated with the genetic hitchhiking of mtDNA haplotype.Therefore,all these characteristics of mtDNA offer the potentials of investigating human origin and evolution.
Previous studies indicated that mtDNA sequences bore strong geographic variation, which was traditionally attributed to the hypothesis of genetic drift.However,the effect of selection on characteristic variation in mtDNA has not yet been proved.The aim in this study by compared between Tibetan and Han populations,and Tibetans in different zones is to detect the signature for natural selection in mitochondrial genome, meaning which and what are the factors for natural selection.
In this study,we focused on 40 Tibetans who generationally resided in Tibet and 50 Han Chinese from Beijing to thoroughly decipher and compare the mtDNA whole sequences between the two populations and the mtDNA sequences(～2 kb) of ATP6, ATP8 and Cyt b genes between the three zone Tibetans.The mtDNA sequences were performed using Applied Biosystems 3730 DNA sequencer.Data in mtDNA were analyzed using softwares phredPhrap 16.0,Network,DnaSP 4.20.2 and SPSS 15.0. The SSPro and SSPro8 softwares were used to predict the protein secondary structure; the 3Dpro software was used to calculate the alpha carbon atom coordinate in PDB format,further the MaxSprout was used to fill the coordinates of other atoms,and finally Rasmol and Swiss-pdbviewer softwares were adopted to compare the structure. The protein stability variation caused by single-locus mutation was predicted by aid of SVM algorithm which was developed by Cheng et al.The structure changes of RNA conferred by mutation were simulated using the RNAfold software.
Our results showed that all the pooled 90 studied subjects pertained to the Macrohaplogroup M and N,and were classified into 13 haplogroups.No differences were observed among all haplogroups between the two populations except for M9 haplogroup.Principal component analysis indicated that the first and second principal components(PC1 and PC2) respectively accounted for 41.3%and 10.7%of the total variance with the added contribution of 52.0%.Further analysis indicated that the Tibetan and Han populations pitched different quadrants,and PC1 and PC2 respectively accounted for 77.1%and 10.1%of the total variance with a total contribution of 87.2%,suggesting obvious geographic differences.
A total of 18 variants were detected by comparing the mtDNA whole sequences between Tibetan and Han populations;of those 5 variants were reported firstly in current study(http://www.mitomap.org) and 8 variants were defined at the internal branch.After predicting the structure changes conferred by the 7 dominated variants in Tibetans,we found that the structures of ND2 G4491A,CO2 G7697A,tRNA alanine T5628C and 12S rRNA A1041G changed significantly after mutation and the stability was increased,meaning the existence of adaptive selection in bioenergetics. Additionally,we constructed the haplotypes of 5 variants harboring D-loop region, and founded that 16145 locus preferred to be combined with the 16255 and 16284 loci, as well as 16234 with 16316.After comparing the replacement of nonsynonumous(N) versus synonymous(S) of 13 peptide-encoded genes among 40 Tibetans,50 Han subjects,144 south Asians and 48 east Asians,we found that the N/S values of the ATP6,ATP8,and Cyt b genes were relatively large(greater than 1) among Tibetans. Significant difference was found for Cyt b gene between Tibetans and south Asians.
In addition,we compared the sequences(～2 kb) of three ATP6,ATP8 and Cyt b genes among Tibetans in three different zones and found that the D or F value was negative using Tajima's D test,Fu and Li's D test and F test,which significant difference was found for ATP6 gene by Fu and Li's F test.We further performed N/S (nonsynonymous(N) versus synonymous(S)) substitutions analysis for these three zones and it provides evidence for the existence of adaptive selection in ATP6 gene and the adaptive selection trend was increased with the increase of altitudes,whereas for the existence of purifying selection in Cyt b gene and the purifying selection trend was increased with the decrease of altitudes.
The analyses of the mtDNA whole sequences and sequences(～2 kb) of three ATP6, ATP8 and Cyt b genes provide clues for the existence of adaptive selection for ATP6, ATP8,ND2(G4491A),CO2(G7697A),tRNA alanine(T5628c) and 12S rRNA (A1041G) genes in Tibetans.The primary factor of natural selection should be the special geographical environment(e.g.,high-altitude,hypoxia,extreme cold) which this Tibetan locates,namely the different geographical environment has the direct selective action on variation of mtDNA.
引文
1. Ruiz-Pesini E, Lott M, Procaccio V, Poole JC, Brandon MC, Mishmar D, Yi C, Kreuziger J, Baldi P, Wallace DC (2007) An enhanced MITOMAP with a global mtDNA mutational phylogeny. Nucleic Acids Res 35:823-828
2. Sun C, Kong QP, Zhang YP (2007) The role of climate in human mitochondrial DNA evolution: A reappraisal. Genomics 89: 338-342
3. Harpending HC, Batzer M, Gueven M, Jorde LB, Rogers AR, Sherry ST (1998) Genetic traces of ancient demography. Proc NatlAcad Sci USA 95:1961-1967
4. Mishmar D, Ruiz-Pesini E, Golik P, Macaulay V, Clark AG, Hosseini S, Brandon M,Easley K, Chen E, Brown MD, Sukernik R, Olckers A, Wallace DC (2003) Natural selection shaped regional mtDNA variation in humans. Proc Natl Acad Sci USA 100:171-176
5. Ruiz-Pesini E, Mishmar D, Brandon M, Procaccio V, Wallace DC (2004) Effects of Purifying and Adaptive Selection on Regional Variation in Human mtDNA. Science 303:223-226
6. Kivisild T, Shen P, Wall DP, Do B, Sung R, Davis K, Passarino G, Underhill PA, Scharfe C, Torroni A, et al (2006)The role of selection in the evolution of human mitochondrial genomes. Genetics 172:373-387
7. Meiklejohn CD, Montooth KL, Rand DM (2007) Positive and negative selection on the mitochondrial genome. Trends Genet 23: 259-263
8. Elson JL, Turnbull, Howell N (2004) Comparative genomic and the evolution of human mitochondrial DNA: assessing the effect of selection.Am J Hum Genet 74: 229-238
9. Ayala FJ (1995) The myth of eve: molecular biology and human origins. Science 270:1930-1936
10. Qian YP, Qian BZ, Su B, Yu JK, Ke YH, Chu ZT, Shi L, Lu DR, Chu JY, Jin L(2000) Multiple origins of Tibetan Y chromosomes. Hum Genet 106: 453-454
11. Yao YG, Zhang YP (2002) Phylogeographic analysis of mtDNA variation in four ethnic populations from Yunnan Province: new data and a reappraisal. J Hum Genet 47: 311-318
12. Chu JY, Huang W, Kuang SQ, Wang JM, Xu JJ, Chu ZT, Yang ZQ, LinKQ, Li P, Wu M, et al (1998) Genetic relationship of population in China. Proc Natl Acad Sci USA 95:11763-11768
13. Yao YG, Kong QP, Bandelt HJ, Kivisild T, Zhang YP (2002) Phylogeographic differentiation of mitochondrial DNA in Han Chinese.Am J Hum Genet 70: 635-651
14. Ewing B, Green P (1998) Base-calling of automated sequencer traces using phred. II.Error probabilities. Genome Res 8:186-194
15. Ewing B, Hillier L, Wendl MC, Green P (1998) Base-calling of automated sequencer traces using phred. I. Accuracy assessment. Genome Res 8:175-185
16. Gordon D, Abajian C, Green P (1998) Consed: a graphical tool for sequence finishing.Genome research 8:195-202
17. Andrews RM, Kubacka I, Chinnery PF, Lightowlers RN, Turnbull DM, Howell N (1999) Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat genet 23:147
18. Kong QP, Bandelt HJ, Sun C, Yao YG, Salas A, Achilli A, Wang CY, Zhong L, Zhu CL,Wu SF (2006) Updating the East Asian mtDNA phylogeny: a prerequisite for the identification of pathogenic mutations. Hum mol genet 15:2076-2086.
19. Wen B, Xie XH, Gao S, Li H, Song XF, Qian TZ, Xiao CJ, Jin JZ, Su B, Lu DR, et al (2004) Analyses of genetic structure of Tibeto-Burman population reveals sex-biased admixture in Southern Tibeto-Burmans.Am J Hum Genet 74: 856-865
20. Ji YL, Jia XY, Zhang QJ, Yao YG (2007) mtDNA haplogroup distribution in Chinese patients with Leber's hereditary optic neuropathy and G11778A mutation. Biochem Bioph Res Co 364: 238-242
21. Pollastri G, Przybylski D, Rost B, Baldi P (2002) Improving the prediction of protein secondary structure in three and eight classes using recurrent neural networks and profiles.Proteins 47:228-235
22. Cheng J, Randall AZ, Sweredoski MJ, Baldi P (2005) SCRATCH: a protein structure and structural feature prediction server. Nucleic Acids Res 33: 72-76
23. Holm L, Sander C (1991) Database algorithm for generating protein backbone and side-chain co-ordinates from a C alpha trace application to model building and detection of co-ordinate errors. J Mol Biol 218:183-194
24. Sayle RA, Milner-White EJ (1995) RASMOL: biomolecular graphics for all. Trends Biochem Sci 20:374
25. Guex N, Peitsch MC (1997) SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis 18:2714-2723
26. Cheng J, Randall A, Baldi P (2006) Prediction of Protein Stability Changes for Single-Site Mutations Using Support Vector Machines. Proteins 62:1125-1132
27. Hofacher IL, Fontana W, Stadler PF, Bonhoeffer S, Tacker M, Schuster P (1994) Fast folding and comparison of RNA secondary structure. Monatshefte f. Chemite 125:167-188
28. Rozas J, Sanchez-DelBarrio JC, Messeguer X, Rozas R (2003) DnaSP, DNA polymorphism analyses by the coalescent and other methods. Bioinformatics 19:2496-2497
29. Kong QP, Yao YG, Sun C, Bandelt HJ, Zhu CL, Zhang YP (2003) Phylogeny of east Asian mitochondrial DNA lineages inferred from complete sequences.Am J Hum Genet 73: 671-676
30. Yao YG, Kong QP, Man XY, Bandelt HJ, Zhang YP (2003) Reconstructing the evolutionary history of China: a caveat about inferences drawn from ancient DNA. Mol Biol Evol 20: 214-219
31. Mitchell AL, Elson JL, Howell N, Taylor RW, Turnbull DM (2006) Sequence variation in mitochondrial complex I genes: mutation or polymorphism?J Med Genet 43:175-179
32. Liu SM, Zhou X, Zheng F, LI X, Liu F, Zhang HM, Xie Y (2007) Novel mutations found in mitochondrial diabetes in Chinese Han population. Diabetes Res Clin Pr 76: 425-435
33. Kong QP, Yao YG, Liu M, Shen SP, Chen C, Zhu CL, Palanichamy, Zhang YP (2003) Mitochondrial DNA sequence polymorphisms of five ethnic populations from northern China. Hum Genet 113: 391-405
34. Yao YG, Salas A, Bravi CM, Bandelt HJ (2006) A reappraisal of complete mtDNA variation in East Asian families with hearing impairment. Hum Genet 119: 505-515
35. Ingman M, Gyllensten U (2001) Analysis of the complete human mtDNA genome: methodology and inferences for human evolution. J Hered 92: 454-461
36. Yao YG, Nie L, Harpending H, Fu YX, Yuan ZG, Zhang YP (2002) Genetic relationship of Chinese ethnic populations revealed by mtDNA sequence diversity. Am J Phys Anthropol 118: 63-76
37. Ruiz-Pesini E, Wallace DC (2006) Evidence for adaptive selection acting on the tRNA and rRNA genes of human mitochondrial DNA. Hum Mutat 27:1072-1081
38. Ingman M, Kaessmann H, Paabo S, Gyllensten U (2000) Mitochondrial genome variation and the origin of modern humans. Nature 408:708-713
39. Ho SYW, Phillips MJ, Cooper A, Drummond A (2005) Time dependence of molecular rate estimates and systematic overestimation of recent divergence times. Mol Biol Evol 22:1561-1568
40. Moilanen JS, Majamaa K (2003) Phylogenetic network and physicochemical properties of nonsynonymous mutations in the protein-coding genes of human mitochondrial DNA. Mol biol Evol 20: 1195-1210
41. Zhu GP, Golding GB,Dean AM (2005) The selective cause of an ancient adaptation.Science 307: 1279-1282
42. KitazumeY, Mutoh M, Shiraki M, Koyama N (2006) Involvement of Lys-308 in the FAD-dependent oxidase activity of NADH dehydrogenase from an alkaliphilic Bacillus.Res Microbiol 157:956-959
43. Cardol P, Lapaille M, Minet P, Franck F, Matagne RF, Remacle C (2006) ND3 and ND4L subunits of mitochondrial complex I, both nucleus encoded in Chlamydomonas reinhardtii, are required for activity and assembly of the enzyme. Eukaryot Cell 5:1460-1467
44. Ugalde C, Hinttala R, Timal S, Smeets R, Rodenburg RJT, Uusimaa J, van Heuvel LP,Nijtmans LGJ, Majamaa K, Smeitink JAM (2007) Mutated ND2 impairs mitochondrial complex I assembly and leads to Leigh Syndrome. Mol Genet Metab 90: 10-14
45. Ballana E, Morales E, Rabionet R, Montserrat B, Ventayol M, Bravo O, Gasparini P,Estivill X (2006) Mitochondrial 12S rRNA gene mutations affect RNA secondary structure and lead to variable penetrance in hearing impairment. Biochem Bioph Res Co 341:950-957
46. Vilmi T, Moilanen JS, Finnila S, Majamaa K (2005) Sequence variation in the tRNA genes of human mitochondrial DNA. J Mol Evol 60:587-597
47. Maca-Meyer N, Gonzalez AM, Larruga JM, Flores C, Cabrera VM (2001) Major genomic mitochondrial lineages delineate early human expansions. BMC Genet 2: 13
48. Liu SM, Zhou X, Zheng F, LI X, Liu F, Zhang HM, Xie Y (2007) Novel mutations found in mitochondrial diabetes in Chinese Han population. Diabetes Res Clin Pr 76: 425—435
49. Sciacco M, Prelle A, Fagiolari G, Bordoni A, Crimi M, Di Fonzo A, Ciscato P, Lamperti C,D'Adda E, Jann S, Bresolin N, Comi G P, Moggio M (2005) A case of CPT deficiency,homoplasmic mtDNA mutation and ragged red fibers at muscle biopsy. J Neuro Sci 239:21-24
50. Tanaka M, Takeyasu T, Fuku N, Li-Jun G, Kurata M (2004) Mitochondrial genome single nucleotide polymorphisms and their phenotypes in the Japanese. Ann NY Acad Sci 1011:7-20
51. Lehtonen MS, Moilanen JS, Majamaa, K (2003) Increased variation in mtDNA in patients with familial sensorineural hearing impairment. Hum Genet 113: 220-227
52. Zhao L, Wang Q, Qian Y, Li R, Cao J, Hart LC, Zhai S, Han D, Young WY, Guan MX (2005) Clinical evaluation and mitochondrial DNA sequence analysis in two Chinese families with aminoglycoside-induced and non-syndromic hearing loss.Biochem Bioph Res Co 336:967-973
53.Li R,Qu J,Zhou X,Tong Y,Hu Y,Qian Y,Lu F,Mo JQ,West C E,Guan M.X(2006)The mitochondrial tRNA(Thr)A15951G mutation may influence the phenotypic expression of the LHON-associated ND4 Gl1778A mutation in a Chinese family.Gene 376:79-86
54.Yoneyama H,Hara T,Kato Y,Yamori T Matsuura ET,Koike K(2005) Nucleotide sequence variation is frequent in the mitochondrial DNA displacement loop region of individual human tumor ceils.Mol Cancer Res 3:14-20
55.Tan DJ,Chang JL,Liu LL,Bail RK,Wang YF,Yeh KT,Wong LJC(2006) Significance of somatic mutations and content alteration of mitochondrial DNA in esophageal cancer.BMC Cancer 6:93-103
56.Bosley TM,Constantinescu CS,Tench CR,Abu-Amero KK(2007) Mitochondrial changes in leukocytes of patients with optic neuritis.Mol Vision 13:1516-1528
57.Torroni A,Miller JA,Moore LG,Zamudio S,Zhuang J,Droma T,Wallace DC(1994)Mitochondrial DNA analysis in Tibet:implications for the origin of the Tibetan population and its adaptation to high altitude.Am J Phys Anthropol 93:189-199.
58.Xu SQ,Yang YZ,Zhou J,Jing GE,Chen YT,Wang J,Yang HM,Yu J,Zheng XG,Ge RL (2005) A mitochondrial genome sequence of the Tibetan antelope(Pantholops hodgsonii).Genomics Proteomics Bioinformatics 3:5-17
59.Popadin K,Polishchuk LV,Mamirova L,Knorre D,Gunbin K(2007) Accumulation of slightly deleterious mutations in mitochondrial protein-coding genes of large versus small mammals.Proc Natl Acad Sci USA 104:13390-13395
60.Yoshino M,Murakami K,Katsumata Y,Takabayashi A,Mori S(1986) Changes in plasma phosphate with the stimulation of anaerobic metabolism in rats during hypoxic-anoxic states.Comp Biochem Physiol A 85:455-457
61.Yoshino M,Kato K,Murakami K,Katsumata Y,Tanaka M,Mori S(1990) Shift of anaerobic to aerobic metabolism in the rats acclimatized to hypoxia.Comp Biochem Physiol A 97:341-344
62.Koch HJ,Raschka C(2005) Influence of moderate altitude on blood lactate and heart rate in a standardized exercise test in healthy volunteers.Acta Physiol Hung 92:139-146
63.Yang Z,Nielsen R,Goldman N,Pedersen AMK(2000) Codon-substitution model for heterogeneous selection pressure at amino acid sites.Genetics 155:431-449
64.Kimura M 1983 The neutral theory of molecular evolution.Cambridge University Press, Cambrige.
65. Schoener TW, Losos JB, Spiller DA (2005) Island biogeography of populations: an introduced species transforms survival patterns. Science 310:1807-1809
66. Losos JB, Schoener TW, Langerhans RB, Spiller DA (2006) Rapid temporal reversal in predator-driven natural selection. Science 314: 1111
67. Zhang C, Bailey DK, Awad T, Liu GY, Xing GL, Cao MQ, Valmeekam V, Retief J,Matsuzaki H, Margaret T, et al (2006) A whole genome long-range haplotype (WGLRH) test for detecting imprints of positive selection in human population. Bioinformatics 22:2122-2128
68. Carlson CS, Thomas DJ, Eberle MA, Swanson JE, Livingston RJ, Rieder MJ, Nickerson DA (2006) Genomic regions exhibiting positive selection identified from dense genotype data. Genome Res 15:1553-1565
69. Ponting CP, Lunter G (2006) Signature of adaptive evolution within human non-coding sequence. Hum Mol Genet 15:170-175
70. Richard SM, Bailliet G, Paez GL, Bianchi MS, Peltomaki P, Bianchi NO (2000) Nuclear and mitochondrial genome instability in human breast cancer. Cancer Res 60: 4231-4237
71. Matoba S, Kang JG, Patino WD, Wragg A, Boehm M, Gavrilova O, Hurley PJ, Bunz F,Hwang PM (2006) p53 regulates mitochondrial respiration. Science 312:1650-1653
72. Yu BP, Chung HY (2006) Adaptive mechanisms to oxidative stress during aging. Mech Ageing Dev 127: 436-443
73. Tower J (2006) Sex-specific regulation of ageing and apoptosis. Mech Ageing Dev 127:705-718
74. Saxena R, de Bakker PIW, Singer K, Mootha V, Burtt N, Hirschhorn JN, Gaudet D,Isomaa B, Daly MJ, Groop L, Ardlie KG, Altshuler D (2006) Comprehensive association testing of common mitochondrial DNA variation in metabolic disease.Am J Hum Genet 79: 54-61
75. Irminger-Finger I (2007) Science of cancer and ageing. J Clin Oncol 25:1844-1851
1. Ayala FJ. The myth of eve: molecular biology and human origins. Science, 1995, 270(5244): 1930-1936.
2. Bamshad M, Wooding SP. Signatures of natural selection in the human genome. Nature Rev Genet, 2003, 4 (2): 99-111.
3. Ingman M, Kaessmann H, Paabo S, Gyllensten U. Mitochondrial genome variation and the origin of modern humans. Nature, 2000,408 (6813): 708-713.
4. Sabeti PC, Reich DE, Higgins JM, Levine HZP, Richter DJ, Schaffner SF, Gabriel SB, Platko JV, Patterson NJ, McDonald GJ, Ackerman HC, Campbell SJ, Altshuler D,Cooperk R, Kwiatkowski D, Ward R, Lander ES. Detecting recent positive selection in the human genome from haplotype structure. Nature, 2002,419 (6909): 832-837.
5. The International HapMap Consortium. A haplotype map of the human genome. Nature,2005, 437 (7063): 1299-1320.
6. The International HapMap Consortium. A second generation human haplotype map of over 3.1 million SNPs. Nature, 2007,449 (7164): 851-861.
7. Jiang Z, Tang H, Ventura M, Cardone MF, Marques-Bonet T, She X, Pevzner PA,Eichler EE. Ancestral reconstruction of segmental duplications reveals punctuated cores of human genome evolution. Nat Genet, 2007,39 (11): 1361-1368.
8. Hawks J, Wang ET, Cochran GM, Harpending HC, Moyzis RK. Recent acceleration of human adaptive evolution. Proc NatlAcad Sci USA, 2007,104 (52): 20753-20758.
9. Sabeti PC, Varilly P, Fry B, Lohmueller J, Hostetter E, Cotsapas C, Xie X, Byrne EH,McCarroll SA, Gaudet R. Genome-wide detection and characterization of positive selection in human populations. Nature, 2007,449 (7164): 913-918.
10. Nielsen R, Hellmann I, Hubisz M, Bustamante C, Clark AG Recent and ongoing selection in the human genome. Nature Rev Genet, 2007, 8 (11): 857-868.
11. Barreiro LB, Laval G, Quach H, Patin E, Quintana-Murci L. Natural selection has driven population differentiation in modern humans. Nat Genet, 2008,40 (3): 340-345.
12. Eriksson A, Fernstrom P, Mehlig B, Sagitov S. An Accurate Model for Genetic Hitchhiking. Genetics, 2008,178 (1): 439-451.
13. Kim PM, Korbel JO, Gerstein MB. Positive selection at the protein network periphery:evaluation in terms of structural constraints and cellular context. Proc Natl Acad Sci USA,2007,104 (51): 20274-20279.
14. Yang Z, Nielsen R. Mutation-selection models of codon substitution and their use to estimate selective strengths on codon usage. Mol Biol Evol, 2008, 25 (3): 568-579.
15. Myles S, Tang K, Somel M, Green RE, Kelso J, Stoneking M. Identification and analysis of genomic regions with large between-population differentiation in humans.Ann Hum Genet, 2008, 72 (Pt 1): 99-110.
16. Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, Higgins J,DeFelice M, Lochner A, Faggart M, Liu-Cordero SN, Rotimi C, Adeyemo A, Cooper R,Ward R, Lander ES, Daly MJ, Altshuler D. The Structure of Haplotype Blocks in the Human Genome. Science, 2002,296 (5576): 2225-2229.
17. Ennis S. Linkage disequilibrium as a tool for detecting signatures of natural selection.Methods Mol Bio, 2007, 376: 59-70.
18. Freudenberg J, Fu YH, Ptacek LJ. Enrichment of HapMap recombination hotspot predictions around human nervous system genes: evidence for positive selection? Europe J Hum Genet, 2007,15 (10): 1071-1078.
19. Kato M, Miya F, Kanemura Y, Tanaka T, Nakamura Y, Tsunoda T. Recombination rates of genes expressed in human tissues. Hum Mol Genet, 2008,17 (4): 577-586.
20. Mishmar D, Ruiz-Pesini E, Golik P, Macaulay V, Clark AG, Hosseini S, Brandon M, Easley K, Chen E, Brown MD, Sukernik RI, Olckers A, Wallace DC. Natural selection shaped regional mtDNA variation in humans. Proc NatlAcad Sci USA, 2003,100 (1):171-176.
21. Ruiz-Pesini E, Mishmar D, Brandon M, Procaccio V, Wallace DC. Effects of Purifying and Adaptive Selection on Regional Variation in Human mtDNA. Science, 2004,303(5655): 223-226.
22. Kivisild T, Shen P, Wall DP, Do B, Sung R, Davis K, Passarino G, Underhill PA, Scharfe C, Torroni A, Scozzari R, Modiano D, Coppa A, de Knijff P, Feldman M, Cavalli-Sforza LL, Oefner PJ. The role of selection in the evolution of human mitochondrial genomes.Genetics, 2006,172 (1): 373-387.
23. Elson JL, Turabull DM, Howell N. Comparative genomic and the evolution of human mitochondrial DNA: assessing the effect of selection. Am J Hum Genet, 2004,74 (2):229-238.
24. Meiklejohn CD, Montooth KL, Rand DM. Positive and negative selection on the mitochondrial genome. Trends Genet, 2007, 23 (6): 259-263.
25. Weir CL, Cockerham CC. Estimating F-statistics for the analysis of population structure.Evolution, 1984,38:1358-1370.
26. Nielsen R. Molecular signatures of natural selection.Ann Rev Genet, 2005, 39:197-218.
27. Kimura M. Evolutionary rate at the molecular level. Nature, 1968, 217 (5129): 624-626.
28. Kimura M. Neutral Theory of Molecular Evolution (Cambridge Univ. Press, Cambridge,UK, 1985).
29. Akey JM, Zhang G, Zhang K, Jin L, Shriver MD. Interrogating a High-Density SNP Map for Signatures of Natural Selection. Genome Res, 2002,12 (12): 1805-1814.
30. Ewing B, Green P. Base-calling of automated sequencer traces using phred. II. Error probabilities. Genome Res, 1998, 8 (3): 186-194.
31. Ewing B, Hillier L, Wendl MC, Green P. Base-calling of automated sequencer traces using phred. I. Accuracy assessment. Genome Res, 1998, 8 (3): 175-185.
32. Andrews RM, Kubacka I, Chinnery PF, Lightowlers RN, Turnbull DM, Howell N.Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nature Genet, 1999,23 (2): 147.
33. Tajima, F. Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics, 1989,123 (3): 585-95.
34. Fu YX, Li WH. Statistical tests of neutrality of mutations. Genetics, 1993,133 (3):693-709.
35. Rozas J, Sanchez-DelBarrio JC, Messeguer X, Rozas R. DNA polymorphism analyses by the coalescent and other methods. Bioinformatics, 2003,19 (18): 2496-2497.
36. Zeng K, Fu YX, Shi S, Wu CI. Statistical tests for detecting positive selection by utilizing high-frequency variants. Genetics, 2006,174 (3): 1431-1439.
37. Fay JC, Wu CI. Hitchhiking under positive Darwinian selection. Genetics, 2000,155 (3):1405-1413.
38. Fu YX. Statistical tests of neutrality of mutations against population growth, hitchhiking and background selection. Genetics, 1997,147 (2): 915-925.
39. Zeng K, Shi S, Wu CI. Compound tests for the detection of hitchhiking under positive selection.Mol BiolEvol, 2007, 24 (8): 1898-1908.
1.Basu A,Lenka N,Mullick J,Avadhani NG.Regulation of murine cytochrome oxidase Vb gene expression in different tissues and during myogenesis.Role of a YY-1factor-binding negative enhancer.J Biol Chem,1997,272(9):5899-5908.
2.Hatefi Y.The mitochondrial electron transport and oxidative phosphorylation system.Annu Rev Biochem,1985,54:1015-1069.
3.Scarpulla RC.Nuclear control of respiratory gene expression in mammalian cells.J Cell Biochem,2006,97(4):673-683.
4.Ackerman SH,Tzagoloff A.Function,structure,and biogenesis of mitochondrial ATP synthase.Prog Nucleic Acid Res Mol Biol,2005,80:95-133.
5. Caruso F, Villa R, Rossi M, Pettinari C, Paduano F, Pennati M, Daidone MG, Zaffaroni N.Mitochondria are primary targets in apoptosis induced by the mixed phosphine gold species chlorotriphenylphosphine-1,3-bis (diphenylphosphino) propanegold (I) in melanoma cell lines. Biochem Pharmacol, 2007,73(6): 773-781.
6. McKenzie M, Liolitsa D, Hanna MG Mitochondrial disease: mutations and mechanisms. Neurochem Res, 2004, 29(3): 589-600.
7. Brandon M, Baldi P, Wallace DC. Mitochondrial mutations in cancer. Oncogene, 2006,25 (34): 4647-4662.
8. Modica-Napolitano JS, Kulawiec M, Singh KK. Mitochondria and human cancer. Curr MolMed, 2007, 7(1): 121-131.
9. Bonawitz ND, Clayton DA, Shadel GS. Initiation and beyond: multiple functions of the human mitochondrial transcription machinery. Mol Cell, 2006,24(6): 813-825.
10. Li K, Neufer PD, Williams RS. Nuclear responses to depletion of mitochondrial DNA in human cells.Am J Physiol Cell Physiol, 1995, 269(5 Pt 1): C1265-C1270.
11. Wallace DC. A mitochondrial paradigm of metabolic and degenerative diseases, aging,and cancer: a dawn for evolutionary medicine.Annu Rev Genet, 2005, 39: 359-407.
12. Calvo S, Jain M, Xie X, Sheth SA, Chang B, Goldberger OA, Spinazzola A, Zeviani M,Carr SA, Mootha VK. Systematic identification of human mitochondrial disease genes through integrative genomics. Nat Genet, 2006,38(5): 576-582.
13. Poyton RO, McEwen JE. Crosstalk between nuclear and mitochondrial genomes.Annu Rev Biochem, 1996, 65: 563-607.
14. Allen S, Balabanidou V, Sideris DP, Lisowsky T, Tokatlidis K. Erv1 mediates the mia40-dependent protein import pathway and provides a functional link to the respiratory chain by shuttling electrons to cytochrome c. J Mol Biol, 2005,353(5): 937-944.
15. Saraste M. Oxidative phosphorylation at the fin de siecle. Science, 1999, 283(5407):1488-1493.
16. Glick B, Schatz G Import of proteins into mitochondria.Annu Rev Genet, 1991, 25:21-44.
17. Liu Z, Butow RA. Mitochondrial retrograde signaling.Annu Rev Genet, 2006,40:159-185.
18. Neupert W. Protein import into mitochondria.Annu Rev Biochem, 1997,66: 863-917.
19. Koehler CM. New developments in mitochondrial assembly. Annu Rev Cell Dev Biol,2004, 20: 309-335.
20. Khalimonchuk O, Rodel G. Biogenesis of cytochrome c oxidase. Mitochondrion, 2005, 5(6): 363-388.
21. Li H, Wang JM, Wilhelmsson H, Hansson A, Thore'n P, Duffy J, Rustin P, Larsson NG Genetic modification of survival in tissuespecific knockout mice with mitochondrial cardiomyopathy.Proc Natl Acad Sci USA, 2000, 97(7): 3467-3472.
22. Scarpulla RC. Transcriptional Paradigms in Mammalian Mitochondrial Biogenesis and Function.Physiol Rev, 2008, 88(2): 611-638.
23. Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM. Acold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell, 1998, 92(6):829-839.
24. Lin J, Tarr PT, Yang R, Rhee J, Puigserver P, Newgard CB, Spiegelman BM. PGC-1beta in the regulation of hepatic glucose and energy metabolism. J Biol Chem, 2003,278(33):30843-30848.
25. Norrbom J, Sundberg CJ, Ameln H, Kraus WE, Jansson E, Gustafsson T. PGC-1alpha mRNA expression is influenced by metabolic perturbation in exercising human skeletal muscle.J Appl Physiol, 2004, 96(1): 189-194.
26. Houten SM, Auwerx J. PGC-lalpha: turbocharging mitochondria. Cell, 2004,119(1):5-7.
27. Liu Z, Butow RA. A transcriptional switch in the expression of yeast tricarboxylic acid cycle genes in response to a reduction or loss of respiratory function. Mol Cell Biol, 1999,19(10): 6720-6728.
28. Amuthan G, Biswas G, Ananadatheerthavarada HK, Vrjayasarathy C, Shephard HM,Avadhani NG Mitochondrial stress-induced calcium signaling, phenotypic changes and invasive behavior in human lung carcinoma A549 cells. Oncogene, 2002, 21(51):7839-7849.
29. Zhao Q, Wang J, Levichkin IV, Stasinopoulos S, Ryan MT, Hoogenraad NJ. Amitochondrial specific stress response in mammalian cells. EMBO J, 2002, 21:4411-4419.
30. Garesse R, Vallejo CG Animal mitochondrial biogenesis and function: a regulatory cross-talk between two genomes. Gene, 2001,263(1-2): 1-16.
31. Scarpulla RC. Transcriptional activators and coactivators in the nuclear control of mitochondrial function in mammalian cells. Gene, 2002,286(1): 81-89.
32. Scarpulla RC. Nuclear activators and co-activators in mammalian mitochondrial biogenesis. Biochim Biophys Acta, 2002,1576(1-2): 1-14.
33. Kelly DP, Scarpulla RC. Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev, 2004,18(4): 357-368.
34. Cam H, Balciunaite E, Blais A, Spektor A, Scarpulla RC, Young R, Kluger Y, Dynlacht BD. A common set of gene regulatory networks links metabolism and growth inhibition.Mol Cell, 2004,16(3): 399-411.
35. Dhar SS, Ongwijitwat S, Wong-Riley MT. Nuclear respiratory factor 1 regulates all ten nuclear-encoded subunits of cytochrome c oxidase in neurons. J Biol Chem, 2008, 283(6):3120-3129.
36. Blesa JR, Prieto-Ruiz JA, Abraham BA, Harrison BL, Hegde AA, Hernandez-Yago J.NRF-1 is the major transcription factor regulating the expression of the human TOMM34 gene. Biochem Cell Biol, 2008, 86(1): 46-56.
37. Ongwijitwat S, Wong-Riley MT. Is nuclear respiratory factor 2 a master transcriptional coordinator for all ten nuclear-encoded cytochrome c oxidase subunits in neurons? Gene,2005, 360(1): 65-77.
38. Larsson NG, Wang J, Wilhelmsson H, Oldfors A, Rustin P, Lewandoski M, Barsh GS,Clayton DA. Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice. Nat Genet, 1998,18(3): 231-236.
39. Ongwijitwat S, Liang HL, Graboyes EM, Wong-Riley MT. Nuclear respiratory factor 2 senses changing cellular energy demands and its silencing down-regulates cytochrome oxidase and other target gene mRNAs. Gene, 2006,374: 39-49.
40. Hayashi R, Ueda T, Farwell MA, Takeuchi N. Nuclear respiratory factor 2 activates transcription of human mitochondrial translation initiation factor 2 gene. Mitochondrion,2007,7(3): 195-203.
41. Borras C, Sastre J, Garcia-Sala D, Lloret A, Pallardo FV, Vina J. Mitochondria from females exhibit higher antioxidant gene expression and lower oxidative damage than males. Free Radic Biol Med, 2003,34(5): 546-552.
42. Vina J, Borras C, Gambini J, Sastre J, Pallardo FV. Why females live longer than males: control of longevity by sex hormones. Sci Aging Knowledge Environ 2005: pe17.
43. Mattingly KA, Ivanova MM, Riggs KA, Wickramasinghe NS, Barch MJ, Klinge CM Estradiol stimulates transcription of nuclear respiratory factor-1 and increases mitochondrial biogenesis. Mol Endocrinol, 2008,22(3): 609-622.
44. Huss JM, Kelly DP. Nuclear receptor signaling and cardiac energetics. Circ Res, 2004,95(6): 568-578.
45. Luo J, Sladek R, Carrier J, Bader JA, Richard D, Giguere V. Reduced fat mass in mice lacking orphan nuclear receptor estrogen- related receptor a. Mol Biol Cell, 2003,23(22): 7947-7956.
46. Mootha VK, Handschin C, Arlow D, Xie X, St Pierre J, Sihag S, Yang W, Altshuler D,Puigserver P, Patterson N, Willy PJ, Schulman IG, Heyman RA, Lander ES, Spiegelman BM. Erralpha and Gabpa/b specify PGC-1alpha-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle. Proc Natl Acad Sci USA, 2004,101(17): 6570-6575.
47. Schreiber SN, Emter R, Hock MB, Knutti D, Cardenas J, Podvinec M, Oakeley EJ, Kralli A. The estrogen-related receptor alpha (ERRalpha) functions in PPARgamma coactivator lalpha (PGC-lalpha)-induced mitochondrial biogenesis. Proc NatlAcad Sci USA, 2004,101(17): 6472-6477.
48. Handschin C, Kobayashi YM, Chin S, Seale P, Campbell KP, Spiegelman BM.PGC-1alpha regulates the neuromuscular junction program and ameliorates Duchenne muscular dystrophy. Genes Dev, 2007, 21(7): 770-783.
49. Barish GD, Narkar VA, Evans RM. PPAR delta: a dagger in the heart of the metabolic syndrome.J Clin Invest, 2006,116(3): 590-597.
50. Vega RB, Kelly DP. A role for estrogen-related receptor alpha in the control of mitochondrial fatty acid beta-oxidation during brown adipocyte differentiation. J Biol Chem, 1997,272(50): 31693-31699.
51. Gopalakrishnan L, Scarpulla RC. Differential regulation of respiratory chain subunits by a CREB-dependent signal transduction pathway. Role of cyclic AMP in cytochrome c and COXIV gene expression. J Biol Chem, 1994,269(1): 105-113.
52. Vercauteren K, Pasko RA, Gleyzer N, Marino VM, Scarpulla RC. PGC-1-related coactivator (PRC): immediate early expression and characterization of a CREB/NRF-1 binding domain associated with cytochrome c promoter occupancy and respiratory growth. Mol Cell Biol, 2006,26(20): 7409-7419.
53. Herzig RP, Scacco S, Scarpulla RC. Sequential serum-dependent activation of CREB and NRF-1 leads to enhanced mitochondrial respiration through the induction of cytochrome c. J Biol Chem, 2000,275(17): 13134-13141.
54. Evans MJ, Scarpulla RC. Interaction of nuclear factors with multiple sites in the somatic cytochrome c promoter. Characterization of upstream NRF-1, ATF and intron Sp1 recognition sites.J Biol Chem, 1989,264(24): 14361-14368.
55. Li R, Luciakova K, Nelson BD. Expression of the human cytochrome c1 gene is controlled through multiple Sp1-binding sites and an initiator region. Eur J Biochem,1996,241(2): 649-656.
56. Li R, Hodny Z, Luciakova K, Barath P, Nelson BD. Sp1 activates and inhibits transcription from separate elements in the proximal promoter of the human adenine nucleotide translocase 2 (ANT2) gene.J Biol Chem, 1996, 271(31): 18925-18930.
57. Zaid A, Li R, Luciakova K, Barath P, Nery S, Nelson BD.On the role of the general transcription factor Spl in the activation and repression of diverse mammalian oxidative phosphorylation genes.J Bioenerg Biomembr, 1999,31(2): 129-135.
58. Morrish F, Giedt C, Hockenbery D. C-MYC apoptotic function is mediated by NRF-1 target genes. Genes Dev, 2003,17(2): 240-255.
59. Li F, Wang Y, Zeller KI, Potter JJ, Wonsey DR, O'Donnell KA, Kim JW, Yustein JT, Lee LA, Dang CV. Myc stimulates nuclearly encoded mitochondrial genes and mitochondrial biogenesis. Mol Cell Biol, 2005, 25(14): 6225-6234.
60. Adhikary S, Eilers M.Transcriptional regulation and transformation by Myc proteins. Nat Rev Mol Cell Biol, 2005, 6(8): 635-645.
61. Lin J, Handschin C, Spiegelman BM. Metabolic control through the PGC-1 family of transcription coactivators. Cel lMetab, 2005,1(6): 361-370.
62. Puigserver P, Spiegelman BM. Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator.Endocr Rev, 2003, 24(1): 78-90.
63. Wu H, Kanatous SB, Thurmond FA, Gallardo T, Isotani E, Bassel-Duby R, Williams RS.Regulation of mitochondrial biogenesis in skeletal muscle by CaMK. Science, 2002,296(5566): 349-352.
64. Andersson U, Scarpulla RC. PGC-1-related coactivator, a novel, serum-inducible coactivator of nuclear respiratory factor 1-dependent transcription in mammalian cells.Mol Cell Biol, 2001,21(11): 3738-3749.
65. Kressler D, Schreiber SN, Knutti D, Kralli A. The PGC-1-related protein PERC is a selective coactivator of estrogen receptor a. J Biol Chem, 2002, 277(16): 13918-13925
66. Lin J, Wu H, Tarr PT, Zhang CY, Wu Z, Boss O, Michael LF, Puigserver P, Isotani E,Olson EN, Lowell BB, Bassel-Duby R, Spiegelman BM. Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature, 2002, 418(6899):797-801.
67. Puigserver P, Adelmant G, Wu Z, Fan M, Xu J, O'Malley B, Spiegelman BM. Activation of PPARgamma coactivator-1 through transcription factor docking. Science, 1999,286(5443): 1368-1371.
68. Monsalve M, Wu Z, Adelmant G, Puigserver P, Fan M, Spiegelman BM. Direct coupling of transcription and mRNA processing through the thermogenic coactivator PGC-1. Mol Cell, 2000,6(2): 307-316.
69. Ristevski S, O'Leary DA, Thornell AP, Owen MJ, Kola I, Hertzog PJ. The ETS transcription factor GABPa is essential for early embryogenesis. Mol Cell Biol, 2004,24(13): 5844-5849.
70. Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, Puigserver P,Carlsson E, Ridderstrale M, Laurila E, Houstis N, Daly MJ, Patterson N, Mesirov JP,Golub TR, Tamayo P, Spiegelman B, Lander ES, Hirschhorn JN, Altshuler D, Groop LC.PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet, 2003,34(3): 267-273
71. Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S,Lowell B, Scarpulla RC, Spiegelman BM. Mechanisms controlling mitochondrial biogenesis and function through the thermogenic coactivator PGC-1. Cell, 1999, 98(1):115-124.
72. Gleyzer N, Vercauteren K, Scarpulla RC. Control of mitochondrial transcription specificity factors (TFB1M and TFB2M) by nuclear respiratory factors (NRF-1 and NRF-2) and PGC-1 family coactivators. Mol Cell Biol, 2005, 25(4): 1354-1366.
73. Biswas G, Adebanjo OA, Freedman BD, Anandatheerthavarada HK, Vijayasarathy C,Zaidi M, Kotlikoff M, Avadhani NG Retrograde Ca2+ signaling in C2C12 skeletal myocytes in response to mitochondrial genetic and metabolic stress: a novel mode of inter-organelle crosstalk. EMBOJ, 1999,18: 522-533.
74. Huss JM, Kelly DP. Nuclear receptor signaling and cardiac energetics. Circ Res, 2004,95(6): 568-578.
75. Ojuka EO, Jones TE, Han DH, Chen M, Wamhoff BR, Sturek M, Holloszy JO.Intermittent increases in cytosolic Ca2+ stimulate mitochondrial biogenesis in muscle cells.Am J Physiol Endocrinol Metab, 2002, 283(5): E1040-E1045.
76. Puigserver P, Rhee J, Lin J, Wu Z, Yoon JC, Zhang CY, Krauss S, Mootha VK, Lowell BB, Spiegelman BM. Cytokine stimulation of energy expenditure through p38 MAP kinase activation of PPARγ coactivator-1. Mol Cell, 2001, 8 (5): 971-982.
77. Knutti D, Kressler D, Kralli A. Regulation of the transcriptional coactivator PGC-1 via MAPK-sensitive interaction with a repressor. Proc NatlAcad Sci USA, 2001, 98 (17):9713-9718
78. Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P. Nutrient control of glucose homeostasis through a complex of PGC-1a and SIRT1. Nature, 2005,434 (7029): 113-118.
79. Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance.Physiol Rev, 2004, 84 (1): 277-359.
80. Akimoto T, Pohnert SC, Li P, Zhang M, Gumbs C, Rosenberg PB, Williams RS, Yan Z.Exercise stimulates PGC-la transcription in skeletal muscle through activation of the p38 MAPK pathway.J Biol Chem, 2005, 280 (20): 19587-19593.
81. Russell AP, Hesselink MK, Lo SK, Schrauwen P. Regulation of metabolic transcriptional co-activators and transcription factors with acute exercise. FASEB J, 2005,19(8):986-988.
82. Wright DC, Han DH, Garcia-Roves PM, Geiger PC, Jones TE, Holloszy JO.Exercise-induced mitochondrial biogenesis begins before the increase in muscle PGC-1a expression.J Biol Chem, 2007,282(1): 194-199.
83. Leone TC, Lehman JJ, Finck BN, Schaeffer PJ, Wende AR, Boudina S, Courtois M,Wozniak DF, Sambandam N, Bernal-Mizrachi C, Chen Z, Holloszy JO, Medeiros DM,Schmidt RE, Saffitz JE, Abel ED, Semenkovich CF, Kelly DP. PGC-la deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis. PLoS Biol, 2005,3(4): e101.
84. Lin J, Wu PH, Tarr PT, Lindenberg KS, St-Pierre J, Zhang CY, Mootha VK, Jager S,Vianna CR, Reznick RM, Cui L, Manieri M, Donovan MX, Wu Z, Cooper MP, Fan MC,Rohas LM, Zavacki AM, Cinti S, Shulman GI, Lowell BB, Krainc D, Spiegelman BM.Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-la null mice. Cell, 2004,119(1): 121-135.
85. Meirhaeghe A, Crowley V, Lenaghan C, Lelliott C, Green K, Stewart A, Hart K, Schinner S, Sethi JK, Yeo G, Brand MD, Cortright RN, O'Rahilly S, Montague C, Vidal-Puig AJ.Characterization of the human, mouse and rat PGC1 β (peroxisome-proliferator-activated receptor-gamma co-activator 1β) gene in vitro and in vivo. Biochem J, 2003,373(Pt 1):155-165.
86. Lin J, Puigserver P, Donovan J, Tan P, Spiegelman BM. Peroxisome proliferator-activated receptor gamma coactivator 1beta (PGC-18), a novel PGC-1-related transcription coactivator associated with host cell factor. J Biol Chem,2002, 277(3): 1645-1648.
87. St-Pierre J, Lin J, Krauss S, Tarr PT, Yang R, Newgard CB, Spiegelman BM.Bioenergetic analysis of peroxisome proliferator-activated receptor gamma coactivators lalpha and lbeta (PGC-la and PGC-1β) in muscle cells.J Biol Chem, 2003,278(29): 26597-26603.
88. Arany Z, Lebrasseur N, Morris C, Smith E, Yang W, Ma Y, Chin S, Spiegelman BM. The transcriptional coactivator PGC-lbeta drives the formation of oxidative type IK fibers in skeletal muscle. Cell Metab, 2007,5(1): 35-46.
89. Sonoda J, Mehl IR, Chong LW, Nofsinger RR, Evans RM. PGC-lbeta controls mitochondrial metabolism to modulate circadian activity, adaptive thermogenesis, and hepatic steatosis. Proc Natl Acad Sci U S A, 2007,104(12): 5223-5228.
90. Arany Z, He H, Lin J, Hoyer K, Handschin C, Toka O, Ahmad F, Matsui T, Chin S, Wu PH, Rybkin II, Shelton JM, Manieri M, Cinti S, Schoen FJ, Bassel-Duby R, Rosenzweig A, Ingwall JS, Spiegelman BM. Transcriptional coactivator PGC-1a controls the energy state and contractile function of cardiac muscle. Cell Metab, 2005,1(4): 259-271.
91. Lee SS, Pineau T, Drago J, Lee EJ, Owens JW, Kroetz DL, Fernandez-Salguero PM,Westphal H, Gonzalez FJ. Targeted disruption of the alpha isoform of the peroxisome proliferatoractivated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators. Mol Cell Biol, 1995,15(6): 3012-3022.
92. Fisher RP, Clayton DA. Purification and characterization of human mitochondrial transcription factor 1. Mol Cell Biol, 1988, 8(8): 3496-3509.
93. Fisher RP, Lisowsky T, Parisi MA, Clayton DA. DNA wrapping and bending by a mitochondrial high mobility group-like transcriptional activator protein.J Biol Chem,1992,267(5): 3358-3367.
94. Parisi MA, Clayton DA. Similarity of human mitochondrial transcription factor 1 to high mobility group proteins. Science, 1991,252(5008): 965-969.
95. Antoshechkin I, Bogenhagen DF, Mastrangelo IA. The HMGbox mitochondrial transcription factor xl-mtTFA binds DNA as a tetramer to activate bidirectional transcription.EMBO J, 1997,16 (11):3198-3206.
96. Dairaghi DJ, Shadel GS, Clayton DA. Addition of a 29 residue carboxyl-terminal tail converts a simple HMG box-containing protein into a transcriptional activator.J Mol Biol, 1995,249(1): 11-28.
97. Alam TI, Kanki T, Muta T, Ukaji K, Abe Y, Nakayama H, Takio K, Hamasaki N, Kang D.Human mitochondrial DNAis packaged with TFAM. Nucleic Acids Res, 2003,31(6):1640-1645.
98. Kaufman BA, Durisic N, Mativetsky JM, Costantino S, Hancock MA, Grutter P,Shoubridge EA. The mitochondrial transcription factor TFAM coordinates the assembly of multiple DNA molecules into nucleoid-like structures. Mol Biol Cell, 2007,18(9): 3225-3236.
99. Garstka HL, Schmitt WE, Schultz J, Sogl B, Silakowski B, Perez-Martos A, Montoya J,Wiesner RJ. Import of mitochondrial transcription factor A (TEAM) into rat liver mitochondria stimulates transcription of mitochondrial DNA. Nucleic Acids Res, 2003,31(17): 5039-5047.
100.Ekstrand MI, Falkenberg M, Rantanen A, Park CB, Gaspari M, Hultenby K, Rustin P,Gustafsson CM, Larsson NG Mitochondrial transcription factor A regulates mtDNA copy number in mammals. Hum Mol Genet, 2004,13(9): 935-944.
101.McCulloch V, Seidel-Rogol BL, Shadel GS. A human mitochondrial transcription factor is related to RNA adenine methyltransferases and binds S-adenosylmethionine. Mol Cell Biol, 2002, 22(4): 1116-1125.
102.Falkenberg M, Gaspari M, Rantanen A, Trifunovic A, Larsson NG, Gustafsson CM.Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA.Nat Genet, 2002,31(3): 289-294.
103.McCulloch V, Shadel GS. Human mitochondrial transcription factor Bl interacts with the C-terminal activation region of hmtTFA and stimulates transcription independently of its RNA methyltransferase activity. Mol Cell Biol, 2003,23(16): 5816-5824.
104.Seidel-Rogol BL, McCulloch V, Shadel GS. Human mitochondrial transcription factor B1 methylates ribosomal RNA at a conserved stem-loop. Nat Genet, 2003,33(1): 23-24.
105.Cotney J, Wang Z, Shadel GS. Relative abundance of the human mitochondrial transcription system and distinct roles for h-mtTFB1 and h-mtTFB2 in mitochondrial biogenesis and gene expression. Nucleic Acids Res, 2007,35(12): 4042-4054.
106.Vanlerberghe GC, Robson CA, Yip JY. Induction of mitochondrial alternative oxidase in response to a cell signal pathway down-regulating the cytochrome pathway prevents programmed cell death. Plant Physiol, 2002,129(4): 1829-1842.
107.Christianson TW, Clayton DA. In vitro transcription of human mitochondrial DNA:accurate termination requires a region of DNA sequence that can function bidirectionally.Proc Natl Acad Sci USA, 1986,83(17): 6277-6281.
108.Daga A, Micol V, Hess D, Aebersold R, Attardi G Molecular characterization of the transcription termination factor from human mitochondria. J Biol Chem, 1993, 268(11):8123-8130.
109.Fernandez-Silva P, Martinez-Azorin F, Micol V, Attardi G The human mitochondrial transcription termination factor (mTERF) is a multizipper protein but binds to DNA as a monomer, with evidence pointing to intramolecular leucine zipper interactions. EMBO J, 1997,16(5): 1066-1079.
110.Asin-Cayuela J, Helm M, Attardi G Amonomer-to-trimer transition of the human mitochondnal transcription termination factor (mTERF) is associated with a loss of in vitro activity.J Biol Chem, 2004, 279(15): 15670-15677.
111.Kruse B, Narasimhan N, Attardi G Termination of transcription in human mitochondria:identification and purification of a DNA binding protein factor that promotes termination.Cell, 1989,58(2): 391-397.
112.Chen Y, Zhou G, Yu M, He Y, Tang W, Lai J, He J, Liu W, Tan D. Cloning and functional analysis of human mTERFL encoding a novel mitochondrial transcription termination factor-like protein. Biochem Biophys Res Commun, 2005, 337(4): 1112-1118.
113.Parikh VS, Morgan MM, Scott R, Clements LS, Butow RA. The mitochondrial genotype can influence nuclear gene expression in yeast. Science, 1987, 235(4788): 576-580.
114.Sekito T, Thornton J, Butow RA. Mitochondria-to-Nuclear Signaling Is Regulated by the Subcellular Localization of the Transcription Factors Rtg1p and Rtg3p. Mol Biol Cell,2000,11(6): 2103-2115.
115.Rothermel BA, Thornton JL, Butow RA. Rtg3p, a basic helix-loop-helix/Ieucine zipper protein that functions in mitochondrial-induced changes in gene expression, contains independent activation domains.J Biol Chem, 1997,272(32): 19801-19807.
116.Koonin EV. Yeast protein controlling inter-organelle communication is related to bacterial phosphatases containing the Hsp 70-type ATP-binding domain. Trends Biochem Sci, 1994,19(4): 156-157
117.Liu Z, Sekito T, Spirek M, Thornton J, Butow RA. Retrograde signaling is regulated by the dynamic interaction between Rtg2p and Mkslp. Mol Cell, 2003,12(2): 401-411.
118.Liu Z, Spirek M, Thornton J, Butow RA. A novel degron-mediated degradation of the RTG pathway regulator, Mkslp, by SCFGrr1. Mol Biol Cell, 2005,16(10): 4893-4904
119.Sekito T, Liu Z, Thornton J, Butow RA. RTG-dependent mitochondria-to-nucleus signaling is regulated by MKS1 and is linked to formation of yeast prion [URE3]. Mol Biol Cell, 2002,13(3): 795-804.
120.Dilova I, Aronova S, Chen JC, Powers T. Tor signaling and nutrient-based signals converge on Mkslp phosphorylation to regulate expression of Rtgl.Rtg3p-dependent target genes.J Biol Chem, 2004,279(45): 46527-46535.
121.Matsuura A, Anraku Y. Characterization of the MKS1 gene, a new negative regulator of the Ras-cyclic AMP pathway in Saccharomyces cerevisiae. Mol Gen Genet, 1993,238(1-2): 6-16.
122.Edskes HK,Wickner RB. A protein required for prion generation: [URE3] induction requires the Ras-regulated Mks1 protein. Proc Natl Acad Sci USA, 2000,97(12):6625-6629.
123.Kroemer G, Reed JC. Mitochondrial control of cell death. Nat Med, 2000, 6(5): 513-519.
124.Leone TC, Lehman JJ, Finck BN, Schaeffer PJ, Wende AR, Boudina S, Courtois M,Wozniak DF, Sambandam N, Bernal-Mizrachi C, Chen Z, Holloszy JO, Medeiros DM,Schmidt RE, Saffitz JE, Abel ED, Semenkovich CF, Kelly DP. PGC-1a deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis. PLoS Biol, 2005, 3(4): e101.
125.Liu Z, Sekito T, Epstein CB, Butow RA. RTG-dependent mitochondria to nucleus signaling is negatively regulated by the seven WD-repeat protein Lst8p. EMBO J, 2001,20(24): 7209-7219.
126.Reinke A, Anderson S, McCaffery JM, Yates J 3rd, Aronova S, Chu S, Fairclough S,Iverson C, Wedaman KP, Powers T. TOR complex 1 includes a novel component, Tco89p (YPL180w), and cooperates with Ssd1p to maintain cellular integrity in Saccharomyces cerevisiae. J Biol Chem, 2004,279(15): 14752-14762.
127.Chen EJ, Kaiser CA. LST8 negatively regulates amino acid biosynthesis as a component of the TOR pathway. J Cell Biol, 2003,161(2): 333-347.
128.Dougherty MK, Morrison DK. Unlocking the code of 14-3-3. J Cell Sci, 2004,117(Pt 10): 1875-1884.
129.Tzivion G, Avruch J. 14-3-3 proteins: active cofactors in cellular regulation by serine/threonine phosphorylation.J Biol Chem, 2002,277(5): 3061-3064.
130.Gelperin D, Weigle J, Nelson K, Roseboom P, Irie K, Matsumoto K, Lemmon S. 14-3-3 proteins: potential roles in vesicular transport and Ras signaling in Saccharomyces cerevisiae. Proc Natl Acad Sci USA, 1995,92(25): 11539-11543.
131.van Heusden GP, Griffiths DJ, Ford JC, Chin-A-Woeng TF, Schrader PA, Carr AM,Steensma HY. The 14-3- 3 proteins encoded by theBMHlandBMH2genes are essential in the yeast Saccharomyces cerevisiae and can be replaced by a plant homologue. Eur J Biochem, 1995, 229(1): 45-53.
132.van Heusden GP, Steensma HY. 14-3-3 Proteins are essential for regulation of RTG3-dependent transcription in Saccharomyces cerevisiae. Yeast, 2001,18(16):1479-1491
133.Butow RA, Avadhani NG Mitochondrial signaling: the retrograde response. Mol Cell,2004,14(1): 1-15.
1.Smith AV,Thomas DJ,Munro HM,et al.Sequence features in regions of weak and strong linkage disequilibrium.Genome Res.,2005;15(11):1519-1534
2.Wall JD,Pritchard JK.Haplotype blocks and linkage disequilibrium in the human genome.Nat Rev Genet,2003,4(8):587-597
3.Anderson EC,Slatkin M.Population-genetic basis of haplotype blocks in the 5q31region.Am J Hum Genet,2004,74:40-49
4.Verhoeven KJ,Simonsen KL.Genomic haplotype blocks may not accurately reflect spatial variation in historic recombination intensity.Mol Biol Evol,2005;22(3):735-740
5.Dawson E,Abecasis GR,Bumpstead S,et al.A first-generation linkage disequilibrium map of human chromosome 22.Nature,2002,418:544-548
6.Clark AG.Inference of haplotypes from PCR-amplified samples of diploid population.Mol Biol Evol,1990,7:111-122
7.Niu T.Algorithms for inferring haplotypes.Genet Epidemiol,2004;27(4):334-347
8.Adams AM,Hudson RR.Maximum-Likelihood Estimation of Demographic Parameters Using the Frequency Spectrum of Unlinked Single-Nucleotide Polymorphisms.Genetics,2004;168(3):1699-1712
9.Meligkotsidou L,Feamhead P.Maximum-Likelihood Estimation of Coalescence Times in Genealogical Trees.Genetics,2005;171(4):2073-2084
10.Tregouet DA,Escolano S,Tiret L,et al.A new algorithm for haplotype-based association analysis:the stochastic-EM algorithm.Ann Hum Genet,2004,68(Pt 2):165-177
11.Sha Q,Dong J,Jiang R,et al.Haplotype sharing transmission/disequilibrium tests that allow for genotyping errors.Genet Epidemiol,2005,28(4):341-351
12.Yang Y,Zhang J,Hoh J,et al.Efficiency of single-nucleotide polymorphism haplotype estimation from pooled DNA. Proc NatlAcad Sci USA, 2003,100(12):7225-7230
13. Zhang Q, Zhao Y, Chen G, Xu Y. Estimate haplotype frequencies in pedigrees. BMC Bioinformatics, 2006,7(Suppl 4):S5 doi:10.1186/1471-2105-7-S4-S5
14. Liu PY, Lu Y and Deng HW. Accurate haplotype inference for multiple linked single-nucleotide polymorphisms using sibship data. Genetics, 2006,174:499-509
15. Stephens M, Smith NJ, Donnelly P. A new statistical method for haplotype reconstruction from population data.Am J Hum Genet, 2001, 68(4):978-989
16. Stephens M, Donnelly P. A comparison of bayesian methods for haplotype reconstruction from population genotype data. Am J Hum Genet, 2003,73(5): 1162-1169
17. Chung RH, Gusfield D. Perfect phylogeny haplotyper: haplotype inferral using a tree model. Bioinformatics, 2003,19(6):780-781
18. Halperin E, Eskin E. Haplotype reconstruction from genotype data using Imperfect Phylogeny. Bioinformatics, 2004, 20(12):1842-1849
19. Niu T, Qin ZS, Xu X, Liu JS. Bayesian haplotype inference for multiple linked single-nucleotide polymorphisms.Am J Hum Genet, 2002, 70(1):157-169
20. Beaumont MA, Rannala B. The Bayesian revolution in genetics. Nat Rev Genet, 2004,5(4):251-261
21. Li SS, Chen JJH and Zhao LP. Empirical vs Bayesian approach for estimating haplotypes from genotypes of unrelated individuals. BMC Genetics, 2007,8:2 doi:10.1186/1471-2156-8-2
22. Lunn DJ, Whittaker JC and Best N. A Bayesian toolkit for genetic association studies.Genetic Epidemiology, 2006,30:231-247
23. Lee PH, Shatkay H. BNTagger: improved tagging SNP selection using Bayesian networks. Bioinformatics, 2006,22(14):e211-e219
24. Qin ZS, Niu T and Liu JS. Partition-ligation-expectation-maximization algorithm for haplotype inference with single nucleotide polymorphisms. Am J Hum Genet, 2002,71(5):1242-1247
25. Sabeti PC, Reich DE, Higgins, et al. Detecting recent positive selection in the human genome from haplotype. Nature, 2002,419:832-837
26. Becker T, Knapp M. Comment on "The impact of genotyping error on haplotype reconstruction and frequency estimation." Eur J Hum Genet, 2003,11(9):637
27. Sobel E, Lange K. Descent graphs in pedigree analysis: application to haplotyping,location scores, and marker-sharing statistics. Am J Hum Genet, 1996,58(6):1323-1337
28. Schaid DJ, McDonnell SK, Wang L, et al. Caution on pedigree haplotype inference with software that assumes linkage equilibrium.Am J Hum Genet, 2002,71(4):992-995
29. Qian D, Beckmann L. Minimum-recombinant haplotyping in pedigrees. Am J Hum Genet, 2002,70(6):1434-1445
30. Kirk KM, Cardon LR. The impact of genotyping error on haplotype reconstruction and frequence estimation. Eur J Hum Genet, 2002,10(10):616-622
31. Zou G, Pan D, Zhao H. Genotyping error detection through tightly linkage markers.Genetics, 2003,164(3):1161-1173
32. Zhou G, Zhai Y, Dong X, et al. Variants in TNFRSF5 locus and association analysis with hepatitis B virus(HBV) infection. Hum Mutat, 2004, 23(1):99-100
33. Kang H, Qin ZS, Niu T, Liu JS. Incorporating genotyping uncertainty in haplotype inference for single-nucleotide polymorphisms.Am J Hum Genet,2004,74(3):495-510
34. Yang Y, Zhang J, Hoh J, et al. Efficiency of single-nucleotide polymorphism haplotype estimation from pooled DNA. Proc NatlAcad Sci USA, 2003,100(12):7225-7230
35. Ito T, Chiku S, Inoue E, et al. Estimation of haplotype frequencies, linkage disequilibrium measures, and combination of haplotype copies in each pool by use of pooled DNA data. Am J Hum Genet, 2003,72(2):384-398
36. De La Vega FM, Isaac H, Collins A, et al. The linkage disequilibrium maps of three human chromosomes across four populations reflect their demographic history and a common underlying recombination pattern. Genome Res, 2005; 15(4): 454-462
37. Falush D, Stephens M, Pritchard JK. Inference of Population Structure Using Multilocus Genotype Data: Linked Loci and Correlated Allele Frequencies. Genetics, 2003; 164(4):1567-1587
38. Zhang K, Calabrese P, Nordborg M, et al. Haplotype block structure and its applications in association studies: Power and study design. Am J Hum Genet, 2002, 71(6):1386-1394.
39. Reich DE, Schaffner SF, Daly MJ, et al. Human genome sequence variation and the influence of gene history, mutation and recombination. Nat Genet,2002,32(1):135-142
40. Ding K, Zhou K, Zhang J, et al. The Effect of Haplotype-Block Definitions on Inference of Haplotype-Block Structure and htSNPs Selection. Mol Biol Evol, 2005; 22(1):148-159
41. Koivisto M, Perola M, Varilo T, et al. An MDL method for finding haplotype blocks and for estimating the strength of haplotype block boundaries. Pac Symp Biocomput, 2003,8:502- 513
42. Patil N, Berno AJ, Hinds DA, et al. Block of limited haplotype diversity revealed by high-resolution scanning of human chromosome 21. Science, 2001, 294:1719-1723
43. Zhang K, Deng M, Chen T, et al. A dynamic programming algorithm for haplotype block partitioning. Proc NatlAcad Sci USA., 2002,99(11): 7335-7339
44. Zhang J, Rowe WL, Struewing JP, et al. HapScope: a software system for automated and visual analysis of functionally annotated haplotypes. Nucleic Acids Res, 2002,30(23):5213-5221
45. Zhang K, Jin L. HaploBlockFinder: haplotype block analyses. Bioinformatics, 2003,19(10):1300-1301.
46. Zhang K, Sun F, Waterman MS, et al. Haplotype block partition with limited resources and applications to human chromosome 21 haplotype data. Am J Hum Genet, 2003,73(1):63-73
47. Ke X, Durrant C, Morris AP, et al. Efficiency and consistency of haplotype tagging of dense SNP maps in multiple samples. Hum Mol Genet, 2004; 13(21): 2557-2565
48. Gabriel SB, Schaffner SF, Nguyen H, et al. The structure of haplotype blocks in the human genome. Science, 2002, 296: 2225-2229
49. Daly MJ, Rioux JD, Schaffner SF, et al. High-resolution haplotype structure in the human genome. Nat Genet, 2001, 29(2): 229-232
50. Ueda H, Howson JM, Esposito L, et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature, 2003,423:506-511
51. Lai E, Bowman C, Bansal A, et al. Medical applications of haplotype-based SNP maps:learning to walk before we run. Nat Genet, 2002, 32(3): 353
52. Bonnen PE, Wang PJ, Kimmel M, et al. Haplotype and linkage disequilibrium architecture for human cancer-associated genes. Genome Res, 2002,12(12): 1846-1853
53. Trikka D, Fang Z, Renwick A, et al. Complex SNP-based haplotypes in three human helicases: implications for cancer association studies. Genome Res., 2002, 12(4):627-639
54. Haiman CA, Strain DO, Pike MC, et al. A comprehensive haplotype analysis of CYP19 and breast cancer risk: the multiethnic cohort. Hum Mol Genet, 2003,12(20): 2679-2692
2. Sun C, Kong QP, Zhang YP (2007) The role of climate in human mitochondrial DNA evolution: A reappraisal. Genomics 89: 338-342
3. Harpending HC, Batzer M, Gueven M, Jorde LB, Rogers AR, Sherry ST (1998) Genetic traces of ancient demography. Proc NatlAcad Sci USA 95:1961-1967
4. Mishmar D, Ruiz-Pesini E, Golik P, Macaulay V, Clark AG, Hosseini S, Brandon M,Easley K, Chen E, Brown MD, Sukernik R, Olckers A, Wallace DC (2003) Natural selection shaped regional mtDNA variation in humans. Proc Natl Acad Sci USA 100:171-176
5. Ruiz-Pesini E, Mishmar D, Brandon M, Procaccio V, Wallace DC (2004) Effects of Purifying and Adaptive Selection on Regional Variation in Human mtDNA. Science 303:223-226
6. Kivisild T, Shen P, Wall DP, Do B, Sung R, Davis K, Passarino G, Underhill PA, Scharfe C, Torroni A, et al (2006)The role of selection in the evolution of human mitochondrial genomes. Genetics 172:373-387
7. Meiklejohn CD, Montooth KL, Rand DM (2007) Positive and negative selection on the mitochondrial genome. Trends Genet 23: 259-263
8. Elson JL, Turnbull, Howell N (2004) Comparative genomic and the evolution of human mitochondrial DNA: assessing the effect of selection.Am J Hum Genet 74: 229-238
9. Ayala FJ (1995) The myth of eve: molecular biology and human origins. Science 270:1930-1936
10. Qian YP, Qian BZ, Su B, Yu JK, Ke YH, Chu ZT, Shi L, Lu DR, Chu JY, Jin L(2000) Multiple origins of Tibetan Y chromosomes. Hum Genet 106: 453-454
11. Yao YG, Zhang YP (2002) Phylogeographic analysis of mtDNA variation in four ethnic populations from Yunnan Province: new data and a reappraisal. J Hum Genet 47: 311-318
12. Chu JY, Huang W, Kuang SQ, Wang JM, Xu JJ, Chu ZT, Yang ZQ, LinKQ, Li P, Wu M, et al (1998) Genetic relationship of population in China. Proc Natl Acad Sci USA 95:11763-11768
13. Yao YG, Kong QP, Bandelt HJ, Kivisild T, Zhang YP (2002) Phylogeographic differentiation of mitochondrial DNA in Han Chinese.Am J Hum Genet 70: 635-651
14. Ewing B, Green P (1998) Base-calling of automated sequencer traces using phred. II.Error probabilities. Genome Res 8:186-194
15. Ewing B, Hillier L, Wendl MC, Green P (1998) Base-calling of automated sequencer traces using phred. I. Accuracy assessment. Genome Res 8:175-185
16. Gordon D, Abajian C, Green P (1998) Consed: a graphical tool for sequence finishing.Genome research 8:195-202
17. Andrews RM, Kubacka I, Chinnery PF, Lightowlers RN, Turnbull DM, Howell N (1999) Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat genet 23:147
18. Kong QP, Bandelt HJ, Sun C, Yao YG, Salas A, Achilli A, Wang CY, Zhong L, Zhu CL,Wu SF (2006) Updating the East Asian mtDNA phylogeny: a prerequisite for the identification of pathogenic mutations. Hum mol genet 15:2076-2086.
19. Wen B, Xie XH, Gao S, Li H, Song XF, Qian TZ, Xiao CJ, Jin JZ, Su B, Lu DR, et al (2004) Analyses of genetic structure of Tibeto-Burman population reveals sex-biased admixture in Southern Tibeto-Burmans.Am J Hum Genet 74: 856-865
20. Ji YL, Jia XY, Zhang QJ, Yao YG (2007) mtDNA haplogroup distribution in Chinese patients with Leber's hereditary optic neuropathy and G11778A mutation. Biochem Bioph Res Co 364: 238-242
21. Pollastri G, Przybylski D, Rost B, Baldi P (2002) Improving the prediction of protein secondary structure in three and eight classes using recurrent neural networks and profiles.Proteins 47:228-235
22. Cheng J, Randall AZ, Sweredoski MJ, Baldi P (2005) SCRATCH: a protein structure and structural feature prediction server. Nucleic Acids Res 33: 72-76
23. Holm L, Sander C (1991) Database algorithm for generating protein backbone and side-chain co-ordinates from a C alpha trace application to model building and detection of co-ordinate errors. J Mol Biol 218:183-194
24. Sayle RA, Milner-White EJ (1995) RASMOL: biomolecular graphics for all. Trends Biochem Sci 20:374
25. Guex N, Peitsch MC (1997) SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis 18:2714-2723
26. Cheng J, Randall A, Baldi P (2006) Prediction of Protein Stability Changes for Single-Site Mutations Using Support Vector Machines. Proteins 62:1125-1132
27. Hofacher IL, Fontana W, Stadler PF, Bonhoeffer S, Tacker M, Schuster P (1994) Fast folding and comparison of RNA secondary structure. Monatshefte f. Chemite 125:167-188
28. Rozas J, Sanchez-DelBarrio JC, Messeguer X, Rozas R (2003) DnaSP, DNA polymorphism analyses by the coalescent and other methods. Bioinformatics 19:2496-2497
29. Kong QP, Yao YG, Sun C, Bandelt HJ, Zhu CL, Zhang YP (2003) Phylogeny of east Asian mitochondrial DNA lineages inferred from complete sequences.Am J Hum Genet 73: 671-676
30. Yao YG, Kong QP, Man XY, Bandelt HJ, Zhang YP (2003) Reconstructing the evolutionary history of China: a caveat about inferences drawn from ancient DNA. Mol Biol Evol 20: 214-219
31. Mitchell AL, Elson JL, Howell N, Taylor RW, Turnbull DM (2006) Sequence variation in mitochondrial complex I genes: mutation or polymorphism?J Med Genet 43:175-179
32. Liu SM, Zhou X, Zheng F, LI X, Liu F, Zhang HM, Xie Y (2007) Novel mutations found in mitochondrial diabetes in Chinese Han population. Diabetes Res Clin Pr 76: 425-435
33. Kong QP, Yao YG, Liu M, Shen SP, Chen C, Zhu CL, Palanichamy, Zhang YP (2003) Mitochondrial DNA sequence polymorphisms of five ethnic populations from northern China. Hum Genet 113: 391-405
34. Yao YG, Salas A, Bravi CM, Bandelt HJ (2006) A reappraisal of complete mtDNA variation in East Asian families with hearing impairment. Hum Genet 119: 505-515
35. Ingman M, Gyllensten U (2001) Analysis of the complete human mtDNA genome: methodology and inferences for human evolution. J Hered 92: 454-461
36. Yao YG, Nie L, Harpending H, Fu YX, Yuan ZG, Zhang YP (2002) Genetic relationship of Chinese ethnic populations revealed by mtDNA sequence diversity. Am J Phys Anthropol 118: 63-76
37. Ruiz-Pesini E, Wallace DC (2006) Evidence for adaptive selection acting on the tRNA and rRNA genes of human mitochondrial DNA. Hum Mutat 27:1072-1081
38. Ingman M, Kaessmann H, Paabo S, Gyllensten U (2000) Mitochondrial genome variation and the origin of modern humans. Nature 408:708-713
39. Ho SYW, Phillips MJ, Cooper A, Drummond A (2005) Time dependence of molecular rate estimates and systematic overestimation of recent divergence times. Mol Biol Evol 22:1561-1568
40. Moilanen JS, Majamaa K (2003) Phylogenetic network and physicochemical properties of nonsynonymous mutations in the protein-coding genes of human mitochondrial DNA. Mol biol Evol 20: 1195-1210
41. Zhu GP, Golding GB,Dean AM (2005) The selective cause of an ancient adaptation.Science 307: 1279-1282
42. KitazumeY, Mutoh M, Shiraki M, Koyama N (2006) Involvement of Lys-308 in the FAD-dependent oxidase activity of NADH dehydrogenase from an alkaliphilic Bacillus.Res Microbiol 157:956-959
43. Cardol P, Lapaille M, Minet P, Franck F, Matagne RF, Remacle C (2006) ND3 and ND4L subunits of mitochondrial complex I, both nucleus encoded in Chlamydomonas reinhardtii, are required for activity and assembly of the enzyme. Eukaryot Cell 5:1460-1467
44. Ugalde C, Hinttala R, Timal S, Smeets R, Rodenburg RJT, Uusimaa J, van Heuvel LP,Nijtmans LGJ, Majamaa K, Smeitink JAM (2007) Mutated ND2 impairs mitochondrial complex I assembly and leads to Leigh Syndrome. Mol Genet Metab 90: 10-14
45. Ballana E, Morales E, Rabionet R, Montserrat B, Ventayol M, Bravo O, Gasparini P,Estivill X (2006) Mitochondrial 12S rRNA gene mutations affect RNA secondary structure and lead to variable penetrance in hearing impairment. Biochem Bioph Res Co 341:950-957
46. Vilmi T, Moilanen JS, Finnila S, Majamaa K (2005) Sequence variation in the tRNA genes of human mitochondrial DNA. J Mol Evol 60:587-597
47. Maca-Meyer N, Gonzalez AM, Larruga JM, Flores C, Cabrera VM (2001) Major genomic mitochondrial lineages delineate early human expansions. BMC Genet 2: 13
48. Liu SM, Zhou X, Zheng F, LI X, Liu F, Zhang HM, Xie Y (2007) Novel mutations found in mitochondrial diabetes in Chinese Han population. Diabetes Res Clin Pr 76: 425—435
49. Sciacco M, Prelle A, Fagiolari G, Bordoni A, Crimi M, Di Fonzo A, Ciscato P, Lamperti C,D'Adda E, Jann S, Bresolin N, Comi G P, Moggio M (2005) A case of CPT deficiency,homoplasmic mtDNA mutation and ragged red fibers at muscle biopsy. J Neuro Sci 239:21-24
50. Tanaka M, Takeyasu T, Fuku N, Li-Jun G, Kurata M (2004) Mitochondrial genome single nucleotide polymorphisms and their phenotypes in the Japanese. Ann NY Acad Sci 1011:7-20
51. Lehtonen MS, Moilanen JS, Majamaa, K (2003) Increased variation in mtDNA in patients with familial sensorineural hearing impairment. Hum Genet 113: 220-227
52. Zhao L, Wang Q, Qian Y, Li R, Cao J, Hart LC, Zhai S, Han D, Young WY, Guan MX (2005) Clinical evaluation and mitochondrial DNA sequence analysis in two Chinese families with aminoglycoside-induced and non-syndromic hearing loss.Biochem Bioph Res Co 336:967-973
53.Li R,Qu J,Zhou X,Tong Y,Hu Y,Qian Y,Lu F,Mo JQ,West C E,Guan M.X(2006)The mitochondrial tRNA(Thr)A15951G mutation may influence the phenotypic expression of the LHON-associated ND4 Gl1778A mutation in a Chinese family.Gene 376:79-86
54.Yoneyama H,Hara T,Kato Y,Yamori T Matsuura ET,Koike K(2005) Nucleotide sequence variation is frequent in the mitochondrial DNA displacement loop region of individual human tumor ceils.Mol Cancer Res 3:14-20
55.Tan DJ,Chang JL,Liu LL,Bail RK,Wang YF,Yeh KT,Wong LJC(2006) Significance of somatic mutations and content alteration of mitochondrial DNA in esophageal cancer.BMC Cancer 6:93-103
56.Bosley TM,Constantinescu CS,Tench CR,Abu-Amero KK(2007) Mitochondrial changes in leukocytes of patients with optic neuritis.Mol Vision 13:1516-1528
57.Torroni A,Miller JA,Moore LG,Zamudio S,Zhuang J,Droma T,Wallace DC(1994)Mitochondrial DNA analysis in Tibet:implications for the origin of the Tibetan population and its adaptation to high altitude.Am J Phys Anthropol 93:189-199.
58.Xu SQ,Yang YZ,Zhou J,Jing GE,Chen YT,Wang J,Yang HM,Yu J,Zheng XG,Ge RL (2005) A mitochondrial genome sequence of the Tibetan antelope(Pantholops hodgsonii).Genomics Proteomics Bioinformatics 3:5-17
59.Popadin K,Polishchuk LV,Mamirova L,Knorre D,Gunbin K(2007) Accumulation of slightly deleterious mutations in mitochondrial protein-coding genes of large versus small mammals.Proc Natl Acad Sci USA 104:13390-13395
60.Yoshino M,Murakami K,Katsumata Y,Takabayashi A,Mori S(1986) Changes in plasma phosphate with the stimulation of anaerobic metabolism in rats during hypoxic-anoxic states.Comp Biochem Physiol A 85:455-457
61.Yoshino M,Kato K,Murakami K,Katsumata Y,Tanaka M,Mori S(1990) Shift of anaerobic to aerobic metabolism in the rats acclimatized to hypoxia.Comp Biochem Physiol A 97:341-344
62.Koch HJ,Raschka C(2005) Influence of moderate altitude on blood lactate and heart rate in a standardized exercise test in healthy volunteers.Acta Physiol Hung 92:139-146
63.Yang Z,Nielsen R,Goldman N,Pedersen AMK(2000) Codon-substitution model for heterogeneous selection pressure at amino acid sites.Genetics 155:431-449
64.Kimura M 1983 The neutral theory of molecular evolution.Cambridge University Press, Cambrige.
65. Schoener TW, Losos JB, Spiller DA (2005) Island biogeography of populations: an introduced species transforms survival patterns. Science 310:1807-1809
66. Losos JB, Schoener TW, Langerhans RB, Spiller DA (2006) Rapid temporal reversal in predator-driven natural selection. Science 314: 1111
67. Zhang C, Bailey DK, Awad T, Liu GY, Xing GL, Cao MQ, Valmeekam V, Retief J,Matsuzaki H, Margaret T, et al (2006) A whole genome long-range haplotype (WGLRH) test for detecting imprints of positive selection in human population. Bioinformatics 22:2122-2128
68. Carlson CS, Thomas DJ, Eberle MA, Swanson JE, Livingston RJ, Rieder MJ, Nickerson DA (2006) Genomic regions exhibiting positive selection identified from dense genotype data. Genome Res 15:1553-1565
69. Ponting CP, Lunter G (2006) Signature of adaptive evolution within human non-coding sequence. Hum Mol Genet 15:170-175
70. Richard SM, Bailliet G, Paez GL, Bianchi MS, Peltomaki P, Bianchi NO (2000) Nuclear and mitochondrial genome instability in human breast cancer. Cancer Res 60: 4231-4237
71. Matoba S, Kang JG, Patino WD, Wragg A, Boehm M, Gavrilova O, Hurley PJ, Bunz F,Hwang PM (2006) p53 regulates mitochondrial respiration. Science 312:1650-1653
72. Yu BP, Chung HY (2006) Adaptive mechanisms to oxidative stress during aging. Mech Ageing Dev 127: 436-443
73. Tower J (2006) Sex-specific regulation of ageing and apoptosis. Mech Ageing Dev 127:705-718
74. Saxena R, de Bakker PIW, Singer K, Mootha V, Burtt N, Hirschhorn JN, Gaudet D,Isomaa B, Daly MJ, Groop L, Ardlie KG, Altshuler D (2006) Comprehensive association testing of common mitochondrial DNA variation in metabolic disease.Am J Hum Genet 79: 54-61
75. Irminger-Finger I (2007) Science of cancer and ageing. J Clin Oncol 25:1844-1851
1. Ayala FJ. The myth of eve: molecular biology and human origins. Science, 1995, 270(5244): 1930-1936.
2. Bamshad M, Wooding SP. Signatures of natural selection in the human genome. Nature Rev Genet, 2003, 4 (2): 99-111.
3. Ingman M, Kaessmann H, Paabo S, Gyllensten U. Mitochondrial genome variation and the origin of modern humans. Nature, 2000,408 (6813): 708-713.
4. Sabeti PC, Reich DE, Higgins JM, Levine HZP, Richter DJ, Schaffner SF, Gabriel SB, Platko JV, Patterson NJ, McDonald GJ, Ackerman HC, Campbell SJ, Altshuler D,Cooperk R, Kwiatkowski D, Ward R, Lander ES. Detecting recent positive selection in the human genome from haplotype structure. Nature, 2002,419 (6909): 832-837.
5. The International HapMap Consortium. A haplotype map of the human genome. Nature,2005, 437 (7063): 1299-1320.
6. The International HapMap Consortium. A second generation human haplotype map of over 3.1 million SNPs. Nature, 2007,449 (7164): 851-861.
7. Jiang Z, Tang H, Ventura M, Cardone MF, Marques-Bonet T, She X, Pevzner PA,Eichler EE. Ancestral reconstruction of segmental duplications reveals punctuated cores of human genome evolution. Nat Genet, 2007,39 (11): 1361-1368.
8. Hawks J, Wang ET, Cochran GM, Harpending HC, Moyzis RK. Recent acceleration of human adaptive evolution. Proc NatlAcad Sci USA, 2007,104 (52): 20753-20758.
9. Sabeti PC, Varilly P, Fry B, Lohmueller J, Hostetter E, Cotsapas C, Xie X, Byrne EH,McCarroll SA, Gaudet R. Genome-wide detection and characterization of positive selection in human populations. Nature, 2007,449 (7164): 913-918.
10. Nielsen R, Hellmann I, Hubisz M, Bustamante C, Clark AG Recent and ongoing selection in the human genome. Nature Rev Genet, 2007, 8 (11): 857-868.
11. Barreiro LB, Laval G, Quach H, Patin E, Quintana-Murci L. Natural selection has driven population differentiation in modern humans. Nat Genet, 2008,40 (3): 340-345.
12. Eriksson A, Fernstrom P, Mehlig B, Sagitov S. An Accurate Model for Genetic Hitchhiking. Genetics, 2008,178 (1): 439-451.
13. Kim PM, Korbel JO, Gerstein MB. Positive selection at the protein network periphery:evaluation in terms of structural constraints and cellular context. Proc Natl Acad Sci USA,2007,104 (51): 20274-20279.
14. Yang Z, Nielsen R. Mutation-selection models of codon substitution and their use to estimate selective strengths on codon usage. Mol Biol Evol, 2008, 25 (3): 568-579.
15. Myles S, Tang K, Somel M, Green RE, Kelso J, Stoneking M. Identification and analysis of genomic regions with large between-population differentiation in humans.Ann Hum Genet, 2008, 72 (Pt 1): 99-110.
16. Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, Higgins J,DeFelice M, Lochner A, Faggart M, Liu-Cordero SN, Rotimi C, Adeyemo A, Cooper R,Ward R, Lander ES, Daly MJ, Altshuler D. The Structure of Haplotype Blocks in the Human Genome. Science, 2002,296 (5576): 2225-2229.
17. Ennis S. Linkage disequilibrium as a tool for detecting signatures of natural selection.Methods Mol Bio, 2007, 376: 59-70.
18. Freudenberg J, Fu YH, Ptacek LJ. Enrichment of HapMap recombination hotspot predictions around human nervous system genes: evidence for positive selection? Europe J Hum Genet, 2007,15 (10): 1071-1078.
19. Kato M, Miya F, Kanemura Y, Tanaka T, Nakamura Y, Tsunoda T. Recombination rates of genes expressed in human tissues. Hum Mol Genet, 2008,17 (4): 577-586.
20. Mishmar D, Ruiz-Pesini E, Golik P, Macaulay V, Clark AG, Hosseini S, Brandon M, Easley K, Chen E, Brown MD, Sukernik RI, Olckers A, Wallace DC. Natural selection shaped regional mtDNA variation in humans. Proc NatlAcad Sci USA, 2003,100 (1):171-176.
21. Ruiz-Pesini E, Mishmar D, Brandon M, Procaccio V, Wallace DC. Effects of Purifying and Adaptive Selection on Regional Variation in Human mtDNA. Science, 2004,303(5655): 223-226.
22. Kivisild T, Shen P, Wall DP, Do B, Sung R, Davis K, Passarino G, Underhill PA, Scharfe C, Torroni A, Scozzari R, Modiano D, Coppa A, de Knijff P, Feldman M, Cavalli-Sforza LL, Oefner PJ. The role of selection in the evolution of human mitochondrial genomes.Genetics, 2006,172 (1): 373-387.
23. Elson JL, Turabull DM, Howell N. Comparative genomic and the evolution of human mitochondrial DNA: assessing the effect of selection. Am J Hum Genet, 2004,74 (2):229-238.
24. Meiklejohn CD, Montooth KL, Rand DM. Positive and negative selection on the mitochondrial genome. Trends Genet, 2007, 23 (6): 259-263.
25. Weir CL, Cockerham CC. Estimating F-statistics for the analysis of population structure.Evolution, 1984,38:1358-1370.
26. Nielsen R. Molecular signatures of natural selection.Ann Rev Genet, 2005, 39:197-218.
27. Kimura M. Evolutionary rate at the molecular level. Nature, 1968, 217 (5129): 624-626.
28. Kimura M. Neutral Theory of Molecular Evolution (Cambridge Univ. Press, Cambridge,UK, 1985).
29. Akey JM, Zhang G, Zhang K, Jin L, Shriver MD. Interrogating a High-Density SNP Map for Signatures of Natural Selection. Genome Res, 2002,12 (12): 1805-1814.
30. Ewing B, Green P. Base-calling of automated sequencer traces using phred. II. Error probabilities. Genome Res, 1998, 8 (3): 186-194.
31. Ewing B, Hillier L, Wendl MC, Green P. Base-calling of automated sequencer traces using phred. I. Accuracy assessment. Genome Res, 1998, 8 (3): 175-185.
32. Andrews RM, Kubacka I, Chinnery PF, Lightowlers RN, Turnbull DM, Howell N.Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nature Genet, 1999,23 (2): 147.
33. Tajima, F. Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics, 1989,123 (3): 585-95.
34. Fu YX, Li WH. Statistical tests of neutrality of mutations. Genetics, 1993,133 (3):693-709.
35. Rozas J, Sanchez-DelBarrio JC, Messeguer X, Rozas R. DNA polymorphism analyses by the coalescent and other methods. Bioinformatics, 2003,19 (18): 2496-2497.
36. Zeng K, Fu YX, Shi S, Wu CI. Statistical tests for detecting positive selection by utilizing high-frequency variants. Genetics, 2006,174 (3): 1431-1439.
37. Fay JC, Wu CI. Hitchhiking under positive Darwinian selection. Genetics, 2000,155 (3):1405-1413.
38. Fu YX. Statistical tests of neutrality of mutations against population growth, hitchhiking and background selection. Genetics, 1997,147 (2): 915-925.
39. Zeng K, Shi S, Wu CI. Compound tests for the detection of hitchhiking under positive selection.Mol BiolEvol, 2007, 24 (8): 1898-1908.
1.Basu A,Lenka N,Mullick J,Avadhani NG.Regulation of murine cytochrome oxidase Vb gene expression in different tissues and during myogenesis.Role of a YY-1factor-binding negative enhancer.J Biol Chem,1997,272(9):5899-5908.
2.Hatefi Y.The mitochondrial electron transport and oxidative phosphorylation system.Annu Rev Biochem,1985,54:1015-1069.
3.Scarpulla RC.Nuclear control of respiratory gene expression in mammalian cells.J Cell Biochem,2006,97(4):673-683.
4.Ackerman SH,Tzagoloff A.Function,structure,and biogenesis of mitochondrial ATP synthase.Prog Nucleic Acid Res Mol Biol,2005,80:95-133.
5. Caruso F, Villa R, Rossi M, Pettinari C, Paduano F, Pennati M, Daidone MG, Zaffaroni N.Mitochondria are primary targets in apoptosis induced by the mixed phosphine gold species chlorotriphenylphosphine-1,3-bis (diphenylphosphino) propanegold (I) in melanoma cell lines. Biochem Pharmacol, 2007,73(6): 773-781.
6. McKenzie M, Liolitsa D, Hanna MG Mitochondrial disease: mutations and mechanisms. Neurochem Res, 2004, 29(3): 589-600.
7. Brandon M, Baldi P, Wallace DC. Mitochondrial mutations in cancer. Oncogene, 2006,25 (34): 4647-4662.
8. Modica-Napolitano JS, Kulawiec M, Singh KK. Mitochondria and human cancer. Curr MolMed, 2007, 7(1): 121-131.
9. Bonawitz ND, Clayton DA, Shadel GS. Initiation and beyond: multiple functions of the human mitochondrial transcription machinery. Mol Cell, 2006,24(6): 813-825.
10. Li K, Neufer PD, Williams RS. Nuclear responses to depletion of mitochondrial DNA in human cells.Am J Physiol Cell Physiol, 1995, 269(5 Pt 1): C1265-C1270.
11. Wallace DC. A mitochondrial paradigm of metabolic and degenerative diseases, aging,and cancer: a dawn for evolutionary medicine.Annu Rev Genet, 2005, 39: 359-407.
12. Calvo S, Jain M, Xie X, Sheth SA, Chang B, Goldberger OA, Spinazzola A, Zeviani M,Carr SA, Mootha VK. Systematic identification of human mitochondrial disease genes through integrative genomics. Nat Genet, 2006,38(5): 576-582.
13. Poyton RO, McEwen JE. Crosstalk between nuclear and mitochondrial genomes.Annu Rev Biochem, 1996, 65: 563-607.
14. Allen S, Balabanidou V, Sideris DP, Lisowsky T, Tokatlidis K. Erv1 mediates the mia40-dependent protein import pathway and provides a functional link to the respiratory chain by shuttling electrons to cytochrome c. J Mol Biol, 2005,353(5): 937-944.
15. Saraste M. Oxidative phosphorylation at the fin de siecle. Science, 1999, 283(5407):1488-1493.
16. Glick B, Schatz G Import of proteins into mitochondria.Annu Rev Genet, 1991, 25:21-44.
17. Liu Z, Butow RA. Mitochondrial retrograde signaling.Annu Rev Genet, 2006,40:159-185.
18. Neupert W. Protein import into mitochondria.Annu Rev Biochem, 1997,66: 863-917.
19. Koehler CM. New developments in mitochondrial assembly. Annu Rev Cell Dev Biol,2004, 20: 309-335.
20. Khalimonchuk O, Rodel G. Biogenesis of cytochrome c oxidase. Mitochondrion, 2005, 5(6): 363-388.
21. Li H, Wang JM, Wilhelmsson H, Hansson A, Thore'n P, Duffy J, Rustin P, Larsson NG Genetic modification of survival in tissuespecific knockout mice with mitochondrial cardiomyopathy.Proc Natl Acad Sci USA, 2000, 97(7): 3467-3472.
22. Scarpulla RC. Transcriptional Paradigms in Mammalian Mitochondrial Biogenesis and Function.Physiol Rev, 2008, 88(2): 611-638.
23. Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM. Acold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell, 1998, 92(6):829-839.
24. Lin J, Tarr PT, Yang R, Rhee J, Puigserver P, Newgard CB, Spiegelman BM. PGC-1beta in the regulation of hepatic glucose and energy metabolism. J Biol Chem, 2003,278(33):30843-30848.
25. Norrbom J, Sundberg CJ, Ameln H, Kraus WE, Jansson E, Gustafsson T. PGC-1alpha mRNA expression is influenced by metabolic perturbation in exercising human skeletal muscle.J Appl Physiol, 2004, 96(1): 189-194.
26. Houten SM, Auwerx J. PGC-lalpha: turbocharging mitochondria. Cell, 2004,119(1):5-7.
27. Liu Z, Butow RA. A transcriptional switch in the expression of yeast tricarboxylic acid cycle genes in response to a reduction or loss of respiratory function. Mol Cell Biol, 1999,19(10): 6720-6728.
28. Amuthan G, Biswas G, Ananadatheerthavarada HK, Vrjayasarathy C, Shephard HM,Avadhani NG Mitochondrial stress-induced calcium signaling, phenotypic changes and invasive behavior in human lung carcinoma A549 cells. Oncogene, 2002, 21(51):7839-7849.
29. Zhao Q, Wang J, Levichkin IV, Stasinopoulos S, Ryan MT, Hoogenraad NJ. Amitochondrial specific stress response in mammalian cells. EMBO J, 2002, 21:4411-4419.
30. Garesse R, Vallejo CG Animal mitochondrial biogenesis and function: a regulatory cross-talk between two genomes. Gene, 2001,263(1-2): 1-16.
31. Scarpulla RC. Transcriptional activators and coactivators in the nuclear control of mitochondrial function in mammalian cells. Gene, 2002,286(1): 81-89.
32. Scarpulla RC. Nuclear activators and co-activators in mammalian mitochondrial biogenesis. Biochim Biophys Acta, 2002,1576(1-2): 1-14.
33. Kelly DP, Scarpulla RC. Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev, 2004,18(4): 357-368.
34. Cam H, Balciunaite E, Blais A, Spektor A, Scarpulla RC, Young R, Kluger Y, Dynlacht BD. A common set of gene regulatory networks links metabolism and growth inhibition.Mol Cell, 2004,16(3): 399-411.
35. Dhar SS, Ongwijitwat S, Wong-Riley MT. Nuclear respiratory factor 1 regulates all ten nuclear-encoded subunits of cytochrome c oxidase in neurons. J Biol Chem, 2008, 283(6):3120-3129.
36. Blesa JR, Prieto-Ruiz JA, Abraham BA, Harrison BL, Hegde AA, Hernandez-Yago J.NRF-1 is the major transcription factor regulating the expression of the human TOMM34 gene. Biochem Cell Biol, 2008, 86(1): 46-56.
37. Ongwijitwat S, Wong-Riley MT. Is nuclear respiratory factor 2 a master transcriptional coordinator for all ten nuclear-encoded cytochrome c oxidase subunits in neurons? Gene,2005, 360(1): 65-77.
38. Larsson NG, Wang J, Wilhelmsson H, Oldfors A, Rustin P, Lewandoski M, Barsh GS,Clayton DA. Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice. Nat Genet, 1998,18(3): 231-236.
39. Ongwijitwat S, Liang HL, Graboyes EM, Wong-Riley MT. Nuclear respiratory factor 2 senses changing cellular energy demands and its silencing down-regulates cytochrome oxidase and other target gene mRNAs. Gene, 2006,374: 39-49.
40. Hayashi R, Ueda T, Farwell MA, Takeuchi N. Nuclear respiratory factor 2 activates transcription of human mitochondrial translation initiation factor 2 gene. Mitochondrion,2007,7(3): 195-203.
41. Borras C, Sastre J, Garcia-Sala D, Lloret A, Pallardo FV, Vina J. Mitochondria from females exhibit higher antioxidant gene expression and lower oxidative damage than males. Free Radic Biol Med, 2003,34(5): 546-552.
42. Vina J, Borras C, Gambini J, Sastre J, Pallardo FV. Why females live longer than males: control of longevity by sex hormones. Sci Aging Knowledge Environ 2005: pe17.
43. Mattingly KA, Ivanova MM, Riggs KA, Wickramasinghe NS, Barch MJ, Klinge CM Estradiol stimulates transcription of nuclear respiratory factor-1 and increases mitochondrial biogenesis. Mol Endocrinol, 2008,22(3): 609-622.
44. Huss JM, Kelly DP. Nuclear receptor signaling and cardiac energetics. Circ Res, 2004,95(6): 568-578.
45. Luo J, Sladek R, Carrier J, Bader JA, Richard D, Giguere V. Reduced fat mass in mice lacking orphan nuclear receptor estrogen- related receptor a. Mol Biol Cell, 2003,23(22): 7947-7956.
46. Mootha VK, Handschin C, Arlow D, Xie X, St Pierre J, Sihag S, Yang W, Altshuler D,Puigserver P, Patterson N, Willy PJ, Schulman IG, Heyman RA, Lander ES, Spiegelman BM. Erralpha and Gabpa/b specify PGC-1alpha-dependent oxidative phosphorylation gene expression that is altered in diabetic muscle. Proc Natl Acad Sci USA, 2004,101(17): 6570-6575.
47. Schreiber SN, Emter R, Hock MB, Knutti D, Cardenas J, Podvinec M, Oakeley EJ, Kralli A. The estrogen-related receptor alpha (ERRalpha) functions in PPARgamma coactivator lalpha (PGC-lalpha)-induced mitochondrial biogenesis. Proc NatlAcad Sci USA, 2004,101(17): 6472-6477.
48. Handschin C, Kobayashi YM, Chin S, Seale P, Campbell KP, Spiegelman BM.PGC-1alpha regulates the neuromuscular junction program and ameliorates Duchenne muscular dystrophy. Genes Dev, 2007, 21(7): 770-783.
49. Barish GD, Narkar VA, Evans RM. PPAR delta: a dagger in the heart of the metabolic syndrome.J Clin Invest, 2006,116(3): 590-597.
50. Vega RB, Kelly DP. A role for estrogen-related receptor alpha in the control of mitochondrial fatty acid beta-oxidation during brown adipocyte differentiation. J Biol Chem, 1997,272(50): 31693-31699.
51. Gopalakrishnan L, Scarpulla RC. Differential regulation of respiratory chain subunits by a CREB-dependent signal transduction pathway. Role of cyclic AMP in cytochrome c and COXIV gene expression. J Biol Chem, 1994,269(1): 105-113.
52. Vercauteren K, Pasko RA, Gleyzer N, Marino VM, Scarpulla RC. PGC-1-related coactivator (PRC): immediate early expression and characterization of a CREB/NRF-1 binding domain associated with cytochrome c promoter occupancy and respiratory growth. Mol Cell Biol, 2006,26(20): 7409-7419.
53. Herzig RP, Scacco S, Scarpulla RC. Sequential serum-dependent activation of CREB and NRF-1 leads to enhanced mitochondrial respiration through the induction of cytochrome c. J Biol Chem, 2000,275(17): 13134-13141.
54. Evans MJ, Scarpulla RC. Interaction of nuclear factors with multiple sites in the somatic cytochrome c promoter. Characterization of upstream NRF-1, ATF and intron Sp1 recognition sites.J Biol Chem, 1989,264(24): 14361-14368.
55. Li R, Luciakova K, Nelson BD. Expression of the human cytochrome c1 gene is controlled through multiple Sp1-binding sites and an initiator region. Eur J Biochem,1996,241(2): 649-656.
56. Li R, Hodny Z, Luciakova K, Barath P, Nelson BD. Sp1 activates and inhibits transcription from separate elements in the proximal promoter of the human adenine nucleotide translocase 2 (ANT2) gene.J Biol Chem, 1996, 271(31): 18925-18930.
57. Zaid A, Li R, Luciakova K, Barath P, Nery S, Nelson BD.On the role of the general transcription factor Spl in the activation and repression of diverse mammalian oxidative phosphorylation genes.J Bioenerg Biomembr, 1999,31(2): 129-135.
58. Morrish F, Giedt C, Hockenbery D. C-MYC apoptotic function is mediated by NRF-1 target genes. Genes Dev, 2003,17(2): 240-255.
59. Li F, Wang Y, Zeller KI, Potter JJ, Wonsey DR, O'Donnell KA, Kim JW, Yustein JT, Lee LA, Dang CV. Myc stimulates nuclearly encoded mitochondrial genes and mitochondrial biogenesis. Mol Cell Biol, 2005, 25(14): 6225-6234.
60. Adhikary S, Eilers M.Transcriptional regulation and transformation by Myc proteins. Nat Rev Mol Cell Biol, 2005, 6(8): 635-645.
61. Lin J, Handschin C, Spiegelman BM. Metabolic control through the PGC-1 family of transcription coactivators. Cel lMetab, 2005,1(6): 361-370.
62. Puigserver P, Spiegelman BM. Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator.Endocr Rev, 2003, 24(1): 78-90.
63. Wu H, Kanatous SB, Thurmond FA, Gallardo T, Isotani E, Bassel-Duby R, Williams RS.Regulation of mitochondrial biogenesis in skeletal muscle by CaMK. Science, 2002,296(5566): 349-352.
64. Andersson U, Scarpulla RC. PGC-1-related coactivator, a novel, serum-inducible coactivator of nuclear respiratory factor 1-dependent transcription in mammalian cells.Mol Cell Biol, 2001,21(11): 3738-3749.
65. Kressler D, Schreiber SN, Knutti D, Kralli A. The PGC-1-related protein PERC is a selective coactivator of estrogen receptor a. J Biol Chem, 2002, 277(16): 13918-13925
66. Lin J, Wu H, Tarr PT, Zhang CY, Wu Z, Boss O, Michael LF, Puigserver P, Isotani E,Olson EN, Lowell BB, Bassel-Duby R, Spiegelman BM. Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature, 2002, 418(6899):797-801.
67. Puigserver P, Adelmant G, Wu Z, Fan M, Xu J, O'Malley B, Spiegelman BM. Activation of PPARgamma coactivator-1 through transcription factor docking. Science, 1999,286(5443): 1368-1371.
68. Monsalve M, Wu Z, Adelmant G, Puigserver P, Fan M, Spiegelman BM. Direct coupling of transcription and mRNA processing through the thermogenic coactivator PGC-1. Mol Cell, 2000,6(2): 307-316.
69. Ristevski S, O'Leary DA, Thornell AP, Owen MJ, Kola I, Hertzog PJ. The ETS transcription factor GABPa is essential for early embryogenesis. Mol Cell Biol, 2004,24(13): 5844-5849.
70. Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, Puigserver P,Carlsson E, Ridderstrale M, Laurila E, Houstis N, Daly MJ, Patterson N, Mesirov JP,Golub TR, Tamayo P, Spiegelman B, Lander ES, Hirschhorn JN, Altshuler D, Groop LC.PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet, 2003,34(3): 267-273
71. Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S,Lowell B, Scarpulla RC, Spiegelman BM. Mechanisms controlling mitochondrial biogenesis and function through the thermogenic coactivator PGC-1. Cell, 1999, 98(1):115-124.
72. Gleyzer N, Vercauteren K, Scarpulla RC. Control of mitochondrial transcription specificity factors (TFB1M and TFB2M) by nuclear respiratory factors (NRF-1 and NRF-2) and PGC-1 family coactivators. Mol Cell Biol, 2005, 25(4): 1354-1366.
73. Biswas G, Adebanjo OA, Freedman BD, Anandatheerthavarada HK, Vijayasarathy C,Zaidi M, Kotlikoff M, Avadhani NG Retrograde Ca2+ signaling in C2C12 skeletal myocytes in response to mitochondrial genetic and metabolic stress: a novel mode of inter-organelle crosstalk. EMBOJ, 1999,18: 522-533.
74. Huss JM, Kelly DP. Nuclear receptor signaling and cardiac energetics. Circ Res, 2004,95(6): 568-578.
75. Ojuka EO, Jones TE, Han DH, Chen M, Wamhoff BR, Sturek M, Holloszy JO.Intermittent increases in cytosolic Ca2+ stimulate mitochondrial biogenesis in muscle cells.Am J Physiol Endocrinol Metab, 2002, 283(5): E1040-E1045.
76. Puigserver P, Rhee J, Lin J, Wu Z, Yoon JC, Zhang CY, Krauss S, Mootha VK, Lowell BB, Spiegelman BM. Cytokine stimulation of energy expenditure through p38 MAP kinase activation of PPARγ coactivator-1. Mol Cell, 2001, 8 (5): 971-982.
77. Knutti D, Kressler D, Kralli A. Regulation of the transcriptional coactivator PGC-1 via MAPK-sensitive interaction with a repressor. Proc NatlAcad Sci USA, 2001, 98 (17):9713-9718
78. Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P. Nutrient control of glucose homeostasis through a complex of PGC-1a and SIRT1. Nature, 2005,434 (7029): 113-118.
79. Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance.Physiol Rev, 2004, 84 (1): 277-359.
80. Akimoto T, Pohnert SC, Li P, Zhang M, Gumbs C, Rosenberg PB, Williams RS, Yan Z.Exercise stimulates PGC-la transcription in skeletal muscle through activation of the p38 MAPK pathway.J Biol Chem, 2005, 280 (20): 19587-19593.
81. Russell AP, Hesselink MK, Lo SK, Schrauwen P. Regulation of metabolic transcriptional co-activators and transcription factors with acute exercise. FASEB J, 2005,19(8):986-988.
82. Wright DC, Han DH, Garcia-Roves PM, Geiger PC, Jones TE, Holloszy JO.Exercise-induced mitochondrial biogenesis begins before the increase in muscle PGC-1a expression.J Biol Chem, 2007,282(1): 194-199.
83. Leone TC, Lehman JJ, Finck BN, Schaeffer PJ, Wende AR, Boudina S, Courtois M,Wozniak DF, Sambandam N, Bernal-Mizrachi C, Chen Z, Holloszy JO, Medeiros DM,Schmidt RE, Saffitz JE, Abel ED, Semenkovich CF, Kelly DP. PGC-la deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis. PLoS Biol, 2005,3(4): e101.
84. Lin J, Wu PH, Tarr PT, Lindenberg KS, St-Pierre J, Zhang CY, Mootha VK, Jager S,Vianna CR, Reznick RM, Cui L, Manieri M, Donovan MX, Wu Z, Cooper MP, Fan MC,Rohas LM, Zavacki AM, Cinti S, Shulman GI, Lowell BB, Krainc D, Spiegelman BM.Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-la null mice. Cell, 2004,119(1): 121-135.
85. Meirhaeghe A, Crowley V, Lenaghan C, Lelliott C, Green K, Stewart A, Hart K, Schinner S, Sethi JK, Yeo G, Brand MD, Cortright RN, O'Rahilly S, Montague C, Vidal-Puig AJ.Characterization of the human, mouse and rat PGC1 β (peroxisome-proliferator-activated receptor-gamma co-activator 1β) gene in vitro and in vivo. Biochem J, 2003,373(Pt 1):155-165.
86. Lin J, Puigserver P, Donovan J, Tan P, Spiegelman BM. Peroxisome proliferator-activated receptor gamma coactivator 1beta (PGC-18), a novel PGC-1-related transcription coactivator associated with host cell factor. J Biol Chem,2002, 277(3): 1645-1648.
87. St-Pierre J, Lin J, Krauss S, Tarr PT, Yang R, Newgard CB, Spiegelman BM.Bioenergetic analysis of peroxisome proliferator-activated receptor gamma coactivators lalpha and lbeta (PGC-la and PGC-1β) in muscle cells.J Biol Chem, 2003,278(29): 26597-26603.
88. Arany Z, Lebrasseur N, Morris C, Smith E, Yang W, Ma Y, Chin S, Spiegelman BM. The transcriptional coactivator PGC-lbeta drives the formation of oxidative type IK fibers in skeletal muscle. Cell Metab, 2007,5(1): 35-46.
89. Sonoda J, Mehl IR, Chong LW, Nofsinger RR, Evans RM. PGC-lbeta controls mitochondrial metabolism to modulate circadian activity, adaptive thermogenesis, and hepatic steatosis. Proc Natl Acad Sci U S A, 2007,104(12): 5223-5228.
90. Arany Z, He H, Lin J, Hoyer K, Handschin C, Toka O, Ahmad F, Matsui T, Chin S, Wu PH, Rybkin II, Shelton JM, Manieri M, Cinti S, Schoen FJ, Bassel-Duby R, Rosenzweig A, Ingwall JS, Spiegelman BM. Transcriptional coactivator PGC-1a controls the energy state and contractile function of cardiac muscle. Cell Metab, 2005,1(4): 259-271.
91. Lee SS, Pineau T, Drago J, Lee EJ, Owens JW, Kroetz DL, Fernandez-Salguero PM,Westphal H, Gonzalez FJ. Targeted disruption of the alpha isoform of the peroxisome proliferatoractivated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators. Mol Cell Biol, 1995,15(6): 3012-3022.
92. Fisher RP, Clayton DA. Purification and characterization of human mitochondrial transcription factor 1. Mol Cell Biol, 1988, 8(8): 3496-3509.
93. Fisher RP, Lisowsky T, Parisi MA, Clayton DA. DNA wrapping and bending by a mitochondrial high mobility group-like transcriptional activator protein.J Biol Chem,1992,267(5): 3358-3367.
94. Parisi MA, Clayton DA. Similarity of human mitochondrial transcription factor 1 to high mobility group proteins. Science, 1991,252(5008): 965-969.
95. Antoshechkin I, Bogenhagen DF, Mastrangelo IA. The HMGbox mitochondrial transcription factor xl-mtTFA binds DNA as a tetramer to activate bidirectional transcription.EMBO J, 1997,16 (11):3198-3206.
96. Dairaghi DJ, Shadel GS, Clayton DA. Addition of a 29 residue carboxyl-terminal tail converts a simple HMG box-containing protein into a transcriptional activator.J Mol Biol, 1995,249(1): 11-28.
97. Alam TI, Kanki T, Muta T, Ukaji K, Abe Y, Nakayama H, Takio K, Hamasaki N, Kang D.Human mitochondrial DNAis packaged with TFAM. Nucleic Acids Res, 2003,31(6):1640-1645.
98. Kaufman BA, Durisic N, Mativetsky JM, Costantino S, Hancock MA, Grutter P,Shoubridge EA. The mitochondrial transcription factor TFAM coordinates the assembly of multiple DNA molecules into nucleoid-like structures. Mol Biol Cell, 2007,18(9): 3225-3236.
99. Garstka HL, Schmitt WE, Schultz J, Sogl B, Silakowski B, Perez-Martos A, Montoya J,Wiesner RJ. Import of mitochondrial transcription factor A (TEAM) into rat liver mitochondria stimulates transcription of mitochondrial DNA. Nucleic Acids Res, 2003,31(17): 5039-5047.
100.Ekstrand MI, Falkenberg M, Rantanen A, Park CB, Gaspari M, Hultenby K, Rustin P,Gustafsson CM, Larsson NG Mitochondrial transcription factor A regulates mtDNA copy number in mammals. Hum Mol Genet, 2004,13(9): 935-944.
101.McCulloch V, Seidel-Rogol BL, Shadel GS. A human mitochondrial transcription factor is related to RNA adenine methyltransferases and binds S-adenosylmethionine. Mol Cell Biol, 2002, 22(4): 1116-1125.
102.Falkenberg M, Gaspari M, Rantanen A, Trifunovic A, Larsson NG, Gustafsson CM.Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA.Nat Genet, 2002,31(3): 289-294.
103.McCulloch V, Shadel GS. Human mitochondrial transcription factor Bl interacts with the C-terminal activation region of hmtTFA and stimulates transcription independently of its RNA methyltransferase activity. Mol Cell Biol, 2003,23(16): 5816-5824.
104.Seidel-Rogol BL, McCulloch V, Shadel GS. Human mitochondrial transcription factor B1 methylates ribosomal RNA at a conserved stem-loop. Nat Genet, 2003,33(1): 23-24.
105.Cotney J, Wang Z, Shadel GS. Relative abundance of the human mitochondrial transcription system and distinct roles for h-mtTFB1 and h-mtTFB2 in mitochondrial biogenesis and gene expression. Nucleic Acids Res, 2007,35(12): 4042-4054.
106.Vanlerberghe GC, Robson CA, Yip JY. Induction of mitochondrial alternative oxidase in response to a cell signal pathway down-regulating the cytochrome pathway prevents programmed cell death. Plant Physiol, 2002,129(4): 1829-1842.
107.Christianson TW, Clayton DA. In vitro transcription of human mitochondrial DNA:accurate termination requires a region of DNA sequence that can function bidirectionally.Proc Natl Acad Sci USA, 1986,83(17): 6277-6281.
108.Daga A, Micol V, Hess D, Aebersold R, Attardi G Molecular characterization of the transcription termination factor from human mitochondria. J Biol Chem, 1993, 268(11):8123-8130.
109.Fernandez-Silva P, Martinez-Azorin F, Micol V, Attardi G The human mitochondrial transcription termination factor (mTERF) is a multizipper protein but binds to DNA as a monomer, with evidence pointing to intramolecular leucine zipper interactions. EMBO J, 1997,16(5): 1066-1079.
110.Asin-Cayuela J, Helm M, Attardi G Amonomer-to-trimer transition of the human mitochondnal transcription termination factor (mTERF) is associated with a loss of in vitro activity.J Biol Chem, 2004, 279(15): 15670-15677.
111.Kruse B, Narasimhan N, Attardi G Termination of transcription in human mitochondria:identification and purification of a DNA binding protein factor that promotes termination.Cell, 1989,58(2): 391-397.
112.Chen Y, Zhou G, Yu M, He Y, Tang W, Lai J, He J, Liu W, Tan D. Cloning and functional analysis of human mTERFL encoding a novel mitochondrial transcription termination factor-like protein. Biochem Biophys Res Commun, 2005, 337(4): 1112-1118.
113.Parikh VS, Morgan MM, Scott R, Clements LS, Butow RA. The mitochondrial genotype can influence nuclear gene expression in yeast. Science, 1987, 235(4788): 576-580.
114.Sekito T, Thornton J, Butow RA. Mitochondria-to-Nuclear Signaling Is Regulated by the Subcellular Localization of the Transcription Factors Rtg1p and Rtg3p. Mol Biol Cell,2000,11(6): 2103-2115.
115.Rothermel BA, Thornton JL, Butow RA. Rtg3p, a basic helix-loop-helix/Ieucine zipper protein that functions in mitochondrial-induced changes in gene expression, contains independent activation domains.J Biol Chem, 1997,272(32): 19801-19807.
116.Koonin EV. Yeast protein controlling inter-organelle communication is related to bacterial phosphatases containing the Hsp 70-type ATP-binding domain. Trends Biochem Sci, 1994,19(4): 156-157
117.Liu Z, Sekito T, Spirek M, Thornton J, Butow RA. Retrograde signaling is regulated by the dynamic interaction between Rtg2p and Mkslp. Mol Cell, 2003,12(2): 401-411.
118.Liu Z, Spirek M, Thornton J, Butow RA. A novel degron-mediated degradation of the RTG pathway regulator, Mkslp, by SCFGrr1. Mol Biol Cell, 2005,16(10): 4893-4904
119.Sekito T, Liu Z, Thornton J, Butow RA. RTG-dependent mitochondria-to-nucleus signaling is regulated by MKS1 and is linked to formation of yeast prion [URE3]. Mol Biol Cell, 2002,13(3): 795-804.
120.Dilova I, Aronova S, Chen JC, Powers T. Tor signaling and nutrient-based signals converge on Mkslp phosphorylation to regulate expression of Rtgl.Rtg3p-dependent target genes.J Biol Chem, 2004,279(45): 46527-46535.
121.Matsuura A, Anraku Y. Characterization of the MKS1 gene, a new negative regulator of the Ras-cyclic AMP pathway in Saccharomyces cerevisiae. Mol Gen Genet, 1993,238(1-2): 6-16.
122.Edskes HK,Wickner RB. A protein required for prion generation: [URE3] induction requires the Ras-regulated Mks1 protein. Proc Natl Acad Sci USA, 2000,97(12):6625-6629.
123.Kroemer G, Reed JC. Mitochondrial control of cell death. Nat Med, 2000, 6(5): 513-519.
124.Leone TC, Lehman JJ, Finck BN, Schaeffer PJ, Wende AR, Boudina S, Courtois M,Wozniak DF, Sambandam N, Bernal-Mizrachi C, Chen Z, Holloszy JO, Medeiros DM,Schmidt RE, Saffitz JE, Abel ED, Semenkovich CF, Kelly DP. PGC-1a deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis. PLoS Biol, 2005, 3(4): e101.
125.Liu Z, Sekito T, Epstein CB, Butow RA. RTG-dependent mitochondria to nucleus signaling is negatively regulated by the seven WD-repeat protein Lst8p. EMBO J, 2001,20(24): 7209-7219.
126.Reinke A, Anderson S, McCaffery JM, Yates J 3rd, Aronova S, Chu S, Fairclough S,Iverson C, Wedaman KP, Powers T. TOR complex 1 includes a novel component, Tco89p (YPL180w), and cooperates with Ssd1p to maintain cellular integrity in Saccharomyces cerevisiae. J Biol Chem, 2004,279(15): 14752-14762.
127.Chen EJ, Kaiser CA. LST8 negatively regulates amino acid biosynthesis as a component of the TOR pathway. J Cell Biol, 2003,161(2): 333-347.
128.Dougherty MK, Morrison DK. Unlocking the code of 14-3-3. J Cell Sci, 2004,117(Pt 10): 1875-1884.
129.Tzivion G, Avruch J. 14-3-3 proteins: active cofactors in cellular regulation by serine/threonine phosphorylation.J Biol Chem, 2002,277(5): 3061-3064.
130.Gelperin D, Weigle J, Nelson K, Roseboom P, Irie K, Matsumoto K, Lemmon S. 14-3-3 proteins: potential roles in vesicular transport and Ras signaling in Saccharomyces cerevisiae. Proc Natl Acad Sci USA, 1995,92(25): 11539-11543.
131.van Heusden GP, Griffiths DJ, Ford JC, Chin-A-Woeng TF, Schrader PA, Carr AM,Steensma HY. The 14-3- 3 proteins encoded by theBMHlandBMH2genes are essential in the yeast Saccharomyces cerevisiae and can be replaced by a plant homologue. Eur J Biochem, 1995, 229(1): 45-53.
132.van Heusden GP, Steensma HY. 14-3-3 Proteins are essential for regulation of RTG3-dependent transcription in Saccharomyces cerevisiae. Yeast, 2001,18(16):1479-1491
133.Butow RA, Avadhani NG Mitochondrial signaling: the retrograde response. Mol Cell,2004,14(1): 1-15.
1.Smith AV,Thomas DJ,Munro HM,et al.Sequence features in regions of weak and strong linkage disequilibrium.Genome Res.,2005;15(11):1519-1534
2.Wall JD,Pritchard JK.Haplotype blocks and linkage disequilibrium in the human genome.Nat Rev Genet,2003,4(8):587-597
3.Anderson EC,Slatkin M.Population-genetic basis of haplotype blocks in the 5q31region.Am J Hum Genet,2004,74:40-49
4.Verhoeven KJ,Simonsen KL.Genomic haplotype blocks may not accurately reflect spatial variation in historic recombination intensity.Mol Biol Evol,2005;22(3):735-740
5.Dawson E,Abecasis GR,Bumpstead S,et al.A first-generation linkage disequilibrium map of human chromosome 22.Nature,2002,418:544-548
6.Clark AG.Inference of haplotypes from PCR-amplified samples of diploid population.Mol Biol Evol,1990,7:111-122
7.Niu T.Algorithms for inferring haplotypes.Genet Epidemiol,2004;27(4):334-347
8.Adams AM,Hudson RR.Maximum-Likelihood Estimation of Demographic Parameters Using the Frequency Spectrum of Unlinked Single-Nucleotide Polymorphisms.Genetics,2004;168(3):1699-1712
9.Meligkotsidou L,Feamhead P.Maximum-Likelihood Estimation of Coalescence Times in Genealogical Trees.Genetics,2005;171(4):2073-2084
10.Tregouet DA,Escolano S,Tiret L,et al.A new algorithm for haplotype-based association analysis:the stochastic-EM algorithm.Ann Hum Genet,2004,68(Pt 2):165-177
11.Sha Q,Dong J,Jiang R,et al.Haplotype sharing transmission/disequilibrium tests that allow for genotyping errors.Genet Epidemiol,2005,28(4):341-351
12.Yang Y,Zhang J,Hoh J,et al.Efficiency of single-nucleotide polymorphism haplotype estimation from pooled DNA. Proc NatlAcad Sci USA, 2003,100(12):7225-7230
13. Zhang Q, Zhao Y, Chen G, Xu Y. Estimate haplotype frequencies in pedigrees. BMC Bioinformatics, 2006,7(Suppl 4):S5 doi:10.1186/1471-2105-7-S4-S5
14. Liu PY, Lu Y and Deng HW. Accurate haplotype inference for multiple linked single-nucleotide polymorphisms using sibship data. Genetics, 2006,174:499-509
15. Stephens M, Smith NJ, Donnelly P. A new statistical method for haplotype reconstruction from population data.Am J Hum Genet, 2001, 68(4):978-989
16. Stephens M, Donnelly P. A comparison of bayesian methods for haplotype reconstruction from population genotype data. Am J Hum Genet, 2003,73(5): 1162-1169
17. Chung RH, Gusfield D. Perfect phylogeny haplotyper: haplotype inferral using a tree model. Bioinformatics, 2003,19(6):780-781
18. Halperin E, Eskin E. Haplotype reconstruction from genotype data using Imperfect Phylogeny. Bioinformatics, 2004, 20(12):1842-1849
19. Niu T, Qin ZS, Xu X, Liu JS. Bayesian haplotype inference for multiple linked single-nucleotide polymorphisms.Am J Hum Genet, 2002, 70(1):157-169
20. Beaumont MA, Rannala B. The Bayesian revolution in genetics. Nat Rev Genet, 2004,5(4):251-261
21. Li SS, Chen JJH and Zhao LP. Empirical vs Bayesian approach for estimating haplotypes from genotypes of unrelated individuals. BMC Genetics, 2007,8:2 doi:10.1186/1471-2156-8-2
22. Lunn DJ, Whittaker JC and Best N. A Bayesian toolkit for genetic association studies.Genetic Epidemiology, 2006,30:231-247
23. Lee PH, Shatkay H. BNTagger: improved tagging SNP selection using Bayesian networks. Bioinformatics, 2006,22(14):e211-e219
24. Qin ZS, Niu T and Liu JS. Partition-ligation-expectation-maximization algorithm for haplotype inference with single nucleotide polymorphisms. Am J Hum Genet, 2002,71(5):1242-1247
25. Sabeti PC, Reich DE, Higgins, et al. Detecting recent positive selection in the human genome from haplotype. Nature, 2002,419:832-837
26. Becker T, Knapp M. Comment on "The impact of genotyping error on haplotype reconstruction and frequency estimation." Eur J Hum Genet, 2003,11(9):637
27. Sobel E, Lange K. Descent graphs in pedigree analysis: application to haplotyping,location scores, and marker-sharing statistics. Am J Hum Genet, 1996,58(6):1323-1337
28. Schaid DJ, McDonnell SK, Wang L, et al. Caution on pedigree haplotype inference with software that assumes linkage equilibrium.Am J Hum Genet, 2002,71(4):992-995
29. Qian D, Beckmann L. Minimum-recombinant haplotyping in pedigrees. Am J Hum Genet, 2002,70(6):1434-1445
30. Kirk KM, Cardon LR. The impact of genotyping error on haplotype reconstruction and frequence estimation. Eur J Hum Genet, 2002,10(10):616-622
31. Zou G, Pan D, Zhao H. Genotyping error detection through tightly linkage markers.Genetics, 2003,164(3):1161-1173
32. Zhou G, Zhai Y, Dong X, et al. Variants in TNFRSF5 locus and association analysis with hepatitis B virus(HBV) infection. Hum Mutat, 2004, 23(1):99-100
33. Kang H, Qin ZS, Niu T, Liu JS. Incorporating genotyping uncertainty in haplotype inference for single-nucleotide polymorphisms.Am J Hum Genet,2004,74(3):495-510
34. Yang Y, Zhang J, Hoh J, et al. Efficiency of single-nucleotide polymorphism haplotype estimation from pooled DNA. Proc NatlAcad Sci USA, 2003,100(12):7225-7230
35. Ito T, Chiku S, Inoue E, et al. Estimation of haplotype frequencies, linkage disequilibrium measures, and combination of haplotype copies in each pool by use of pooled DNA data. Am J Hum Genet, 2003,72(2):384-398
36. De La Vega FM, Isaac H, Collins A, et al. The linkage disequilibrium maps of three human chromosomes across four populations reflect their demographic history and a common underlying recombination pattern. Genome Res, 2005; 15(4): 454-462
37. Falush D, Stephens M, Pritchard JK. Inference of Population Structure Using Multilocus Genotype Data: Linked Loci and Correlated Allele Frequencies. Genetics, 2003; 164(4):1567-1587
38. Zhang K, Calabrese P, Nordborg M, et al. Haplotype block structure and its applications in association studies: Power and study design. Am J Hum Genet, 2002, 71(6):1386-1394.
39. Reich DE, Schaffner SF, Daly MJ, et al. Human genome sequence variation and the influence of gene history, mutation and recombination. Nat Genet,2002,32(1):135-142
40. Ding K, Zhou K, Zhang J, et al. The Effect of Haplotype-Block Definitions on Inference of Haplotype-Block Structure and htSNPs Selection. Mol Biol Evol, 2005; 22(1):148-159
41. Koivisto M, Perola M, Varilo T, et al. An MDL method for finding haplotype blocks and for estimating the strength of haplotype block boundaries. Pac Symp Biocomput, 2003,8:502- 513
42. Patil N, Berno AJ, Hinds DA, et al. Block of limited haplotype diversity revealed by high-resolution scanning of human chromosome 21. Science, 2001, 294:1719-1723
43. Zhang K, Deng M, Chen T, et al. A dynamic programming algorithm for haplotype block partitioning. Proc NatlAcad Sci USA., 2002,99(11): 7335-7339
44. Zhang J, Rowe WL, Struewing JP, et al. HapScope: a software system for automated and visual analysis of functionally annotated haplotypes. Nucleic Acids Res, 2002,30(23):5213-5221
45. Zhang K, Jin L. HaploBlockFinder: haplotype block analyses. Bioinformatics, 2003,19(10):1300-1301.
46. Zhang K, Sun F, Waterman MS, et al. Haplotype block partition with limited resources and applications to human chromosome 21 haplotype data. Am J Hum Genet, 2003,73(1):63-73
47. Ke X, Durrant C, Morris AP, et al. Efficiency and consistency of haplotype tagging of dense SNP maps in multiple samples. Hum Mol Genet, 2004; 13(21): 2557-2565
48. Gabriel SB, Schaffner SF, Nguyen H, et al. The structure of haplotype blocks in the human genome. Science, 2002, 296: 2225-2229
49. Daly MJ, Rioux JD, Schaffner SF, et al. High-resolution haplotype structure in the human genome. Nat Genet, 2001, 29(2): 229-232
50. Ueda H, Howson JM, Esposito L, et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature, 2003,423:506-511
51. Lai E, Bowman C, Bansal A, et al. Medical applications of haplotype-based SNP maps:learning to walk before we run. Nat Genet, 2002, 32(3): 353
52. Bonnen PE, Wang PJ, Kimmel M, et al. Haplotype and linkage disequilibrium architecture for human cancer-associated genes. Genome Res, 2002,12(12): 1846-1853
53. Trikka D, Fang Z, Renwick A, et al. Complex SNP-based haplotypes in three human helicases: implications for cancer association studies. Genome Res., 2002, 12(4):627-639
54. Haiman CA, Strain DO, Pike MC, et al. A comprehensive haplotype analysis of CYP19 and breast cancer risk: the multiethnic cohort. Hum Mol Genet, 2003,12(20): 2679-2692