Identifying Signatures of Natural Selection in Tibetan and Andean Populations Using Dense Genome Scan Data

作者：Abigail W. Bigham, Marc Bauchet, Dalila Pinto, Xianyun Mao, Joshua M. Akey, Rui Mei, Stephen W. Scherer, Colleen G. Julian, Megan J. Wilson, David López Herráez, Tom D. Brutsaert, Esteban J. Parra, Lorna G. Moore, Mark D. Shriver · 发表于：PLoS Genetics · 年份：2010 · DOI：10.1371/journal.pgen.1001116 · 被引用次数：619 · 研究领域：High Altitude and Hypoxia、Cancer, Hypoxia, and Metabolism、Mitochondrial Function and Pathology

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 selectio...