Identifying positive selection candidate loci for high-altitude adaptation in Andean populations.
Identifying positive selection candidate loci for high-altitude adaptation in Andean populations.
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DOI：
10.1186/1479-7364-4-2-79
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发表时间：
2009-12
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 AW;Mao X;Mei R;Brutsaert T;Wilson MJ;Julian CG;Parra EJ;Akey JM;Moore LG;Shriver MD
高海拔环境(2500米)为科学家提供了一个天然实验室，以研究低环境氧分压对人类群体的生理和遗传影响。了解高海拔生命如何影响人类新陈代谢的一种方法是调查全基因组数据集，以寻找自然选择的特征。在这项工作中，我们报告了一项研究，目的是在一个高原群体--来自南美高原的安第斯人--中确定与低氧适应有关的被选择提名的候选基因。我们分析了密集的微阵列基因数据，使用了四个检测偏离中性的测试统计数据。使用候选基因，基于单核苷酸多态的方法，我们确定了在这个群体中表现出最近遗传适应的初步证据的基因。这些基因包括低氧诱导转录因子(HIF)途径的一部分，这是一种涉及氧稳态的生化途径，以及其他三个以前未知与高海拔表型相关的基因组区域。除了确定被选择提名的候选基因外，我们还测试了HIF途径是否显示出自然选择的证据。我们的结果表明，这一生化途径的基因作为一个群体，没有证据表明安第斯人是在低氧条件下进化的。然而，来自特定HIF靶向基因的结果表明，这一途径中的基因可能在安第斯山脉适应高海拔环境中发挥作用，即使这条途径作为一个整体并没有表现出更高的相对进化速度。这些数据提示了基因在高海拔适应中的作用，并为基因/表型关联研究提供了基础，这些研究对于确认假定的自然选择候选基因和基因区在适应海拔中的作用是必要的。
High-altitude environments (>2,500 m) provide scientists with a natural laboratory to study the physiological and genetic effects of low ambient oxygen tension on human populations. One approach to understanding how life at high altitude has affected human metabolism is to survey genome-wide datasets for signatures of natural selection. In this work, we report on a study to identify selection-nominated candidate genes involved in adaptation to hypoxia in one highland group, Andeans from the South American Altiplano. We analysed dense microarray genotype data using four test statistics that detect departures from neutrality. Using a candidate gene, single nucleotide polymorphism-based approach, we identified genes exhibiting preliminary evidence of recent genetic adaptation in this population. These included genes that are part of the hypoxia-inducible transcription factor (HIF) pathway, a biochemical pathway involved in oxygen homeostasis, as well as three other genomic regions previously not known to be associated with high-altitude phenotypes. In addition to identifying selection-nominated candidate genes, we also tested whether the HIF pathway shows evidence of natural selection. Our results indicate that the genes of this biochemical pathway as a group show no evidence of having evolved in response to hypoxia in Andeans. Results from particular HIF-targeted genes, however, suggest that genes in this pathway could play a role in Andean adaptation to high altitude, even if the pathway as a whole does not show higher relative rates of evolution. These data suggest a genetic role in high-altitude adaptation and provide a basis for genotype/phenotype association studies that are necessary to confirm the role of putative natural selection candidate genes and gene regions in adaptation to altitude.