Identifying signatures of natural selection in Tibetan and Andean populations using dense genome scan data.
Identifying signatures of natural selection in Tibetan and Andean populations using dense genome scan data.
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DOI：
10.1371/journal.pgen.1001116
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发表时间：
2010-09-09
期刊：
影响因子：
4.5
通讯作者：
Shriver MD
中科院分区：
文献类型：
--
作者：
Bigham A;Bauchet M;Pinto D;Mao X;Akey JM;Mei R;Scherer SW;Julian CG;Wilson MJ;López Herráez D;Brutsaert T;Parra EJ;Moore LG;Shriver MD
高海拔缺氧（由于气压降低导致吸入氧张力降低）对人体产生严重的生理压力。两个人类已经生活了几千年的高海拔地区是安第斯高原和青藏高原。生活在这些地区的人群表现出独特的循环，呼吸和血液适应高海拔生活。虽然这些反应已经很好地表征了生理学，但其潜在的遗传基础仍然未知。我们进行了基因组扫描，以确定基因显示适应缺氧的证据。我们研究了每条染色体，以确定与海拔表型相关的基因组区域，这些基因组区域具有以前未知的功能。此外，在氧代谢和传感功能的基因组进行了检查，以测试的假设，特定的途径已参与遗传适应海拔。应用4种常用的群体遗传统计方法，分别对安第斯人和藏族人的选择候选基因和基因区域进行了鉴定。西藏人和安第斯人的遗传适应模式在很大程度上是不同的，两个种群都在不同的基因或基因区域中显示出积极的自然选择的证据。有趣的是，一个先前已知在细胞氧传感中很重要的基因EGLN 1（也称为PHD 2）在西藏人和安第斯人中都显示出正选择的证据。然而，该基因的变异模式在两个种群之间不同。我们的研究结果表明，几个关键的HIF调控和靶基因负责适应安第斯山脉和西藏的高海拔地区，和几个不同的染色体区域牵连在假定的选择反应。这些数据表明，在高海拔适应的遗传作用，并为未来的基因型/表型关联研究，以确认选择提名的候选基因和基因区域在适应海拔高度的作用提供了基础。高原缺氧是由于在高海拔地区大气压力降低而引起的，对人体造成严重的生理应激。有三个人类种群在高海拔地区居住了数千年，包括安第斯高原上的安第斯人、喜马拉雅高原上的西藏人和塞米亚高原上的埃塞俄比亚高地人。这些人群中的每一个都表现出一套独特的生理变化，以减少在海拔高度的氧气。然而，我们才刚刚开始了解导致观察到的生理学的遗传变化。目前研究的目的是确定安第斯人和西藏人可能参与适应高海拔的基因区域。分别在这两个高海拔人群中发现了显示最近正选择证据的基因组区域。我们发现了令人信服的证据，在HIF途径基因的正选择，在珠蛋白簇位于11号染色体上，并在几个染色体区域的安第斯人和西藏人。我们的研究结果表明，关键的HIF调节和靶基因负责适应海拔高度和牵连几个不同的染色体区域。在安第斯人和藏人中发现的候选基因和基因区域在很大程度上彼此不同。然而，一个HIF途径基因，EGLN 1，显示在两个高海拔人群中的定向选择的证据。
High-altitude hypoxia (reduced inspired oxygen tension due to decreased barometric pressure) exerts severe physiological stress on the human body. Two high-altitude regions where humans have lived for millennia are the Andean Altiplano and the Tibetan Plateau. Populations living in these regions exhibit unique circulatory, respiratory, and hematological adaptations to life at high altitude. Although these responses have been well characterized physiologically, their underlying genetic basis remains unknown. We performed a genome scan to identify genes showing evidence of adaptation to hypoxia. We looked across each chromosome to identify genomic regions with previously unknown function with respect to altitude phenotypes. In addition, groups of genes functioning in oxygen metabolism and sensing were examined to test the hypothesis that particular pathways have been involved in genetic adaptation to altitude. Applying four population genetic statistics commonly used for detecting signatures of natural selection, we identified selection-nominated candidate genes and gene regions in these two populations (Andeans and Tibetans) separately. The Tibetan and Andean patterns of genetic adaptation are largely distinct from one another, with both populations showing evidence of positive natural selection in different genes or gene regions. Interestingly, one gene previously known to be important in cellular oxygen sensing, EGLN1 (also known as PHD2), shows evidence of positive selection in both Tibetans and Andeans. However, the pattern of variation for this gene differs between the two populations. Our results indicate that several key HIF-regulatory and targeted genes are responsible for adaptation to high altitude in Andeans and Tibetans, and several different chromosomal regions are implicated in the putative response to selection. These data suggest a genetic role in high-altitude adaption and provide a basis for future genotype/phenotype association studies necessary to confirm the role of selection-nominated candidate genes and gene regions in adaptation to altitude. High-altitude hypoxia is caused by decreased barometric pressure at high altitude, and results in severe physiological stress to the human body. Three human populations have resided at high altitude for millennia including Andeans on the Andean Altiplano, Tibetans on the Himalayan plateau, and Ethiopian highlanders on the Semian Plateau. Each of these populations exhibits a unique suite of physiological changes to the decreased oxygen available at altitude. However, we are just beginning to understand the genetic changes responsible for the observed physiology. The aim of the current study was to identify gene regions that may be involved in adaptation to high altitude in both Andeans and Tibetans. Genomic regions showing evidence of recent positive selection were identified in these two high-altitude human groups separately. We found compelling evidence of positive selection in HIF pathway genes, in the globin cluster located on chromosome 11, and in several chromosomal regions for Andeans and Tibetans. Our results suggest that key HIF regulatory and targeted genes are responsible for adaptation to altitude and implicate several distinct chromosomal regions. The candidate genes and gene regions identified in Andeans and Tibetans are largely distinct from one another. However, one HIF pathway gene, EGLN1, shows evidence of directional selection in both high-altitude populations.
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影响因子：
56.9
作者：
Jaakkola, P;Mole, DR;Ratcliffe, PJ
通讯作者：
Ratcliffe, PJ
影响因子：
3.7
作者：
López Herráez D;Bauchet M;Tang K;Theunert C;Pugach I;Li J;Nandineni MR;Gross A;Scholz M;Stoneking M
通讯作者：
Stoneking M
影响因子：
5.4
作者：
Gesang, L;Liu, GZ;Chan, Y
通讯作者：
Chan, Y
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y