Sequencing of 50 Human Exomes Reveals Adaptation to High Altitude Xin Yi Science DOI 10 1126 science 1190371 et al 329 75 2010 This copy is for your personal non commercial use only including high resolution figures can be found in the online If you wish to distribute this article to others colleagues clients or customers by clicking here you can order high quality copies for your can be obtained by here Permission to republish or repurpose articles or portions of articles following the guidelines The following resources related to this article are available online at www sciencemag org this information is current as of Updated information and services version of this article at http www sciencemag org content 329 5987 75 full html February 7 2014 Supporting Online Material http www sciencemag org content suppl 2010 06 29 329 5987 75 DC1 html can be found at A list of selected additional articles on the Science Web sites found at http www sciencemag org content 329 5987 75 full html 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Association for the Advancement of Science 1200 New York Avenue NW Washington DC 20005 2010 by the American Association for the Advancement of Science all rights reserved The title is a registered trademark of AAAS Science REPORTS Digestive and Kidney Diseases and The University of Luxembourg Institute for Systems Biology Program to C D H T S S was supported by NIH Genetics Training Grant T32 All studies have been performed with informed consent approved by the Institutional Board of Qinghai Medical College of Qinghai University in Xining Qinghai Province People s Republic of China All SNP genoptypes are deposited in Gene Expression Omnibus with accession code GSE21661 These data as well as phenotype data are also available on our laboratory Web site http jorde lab genetics utah edu Please contact R L G for access to DNA samples Figs S1 to S6 Tables S1 to S12 References Supporting Online Material www sciencemag org cgi content full science 1189406 DC1 Materials and Methods 10 March 2010 accepted 6 May 2010 Published online 13 May 2010 10 1126 science 1189406 Include this information when citing this paper Sequencing of 50 Human Exomes Reveals Adaptation to High Altitude Xin Yi 1 2 Yu Liang 1 2 Emilia Huerta Sanchez 3 Xin Jin 1 4 Zha Xi Ping Cuo 2 5 John E Pool 3 6 Xun Xu 1 Hui Jiang 1 Nicolas Vinckenbosch 3 Thorfinn Sand Korneliussen 7 Hancheng Zheng 1 4 Tao Liu 1 Weiming He 1 8 Kui Li 2 5 Ruibang Luo 1 4 Xifang Nie 1 Honglong Wu 1 9 Meiru Zhao 1 Hongzhi Cao 1 9 Jing Zou 1 Ying Shan 1 4 Shuzheng Li 1 Qi Yang 1 Asan 1 2 Peixiang Ni 1 Geng Tian 1 2 Junming Xu 1 Xiao Liu 1 Tao Jiang 1 9 Renhua Wu 1 Guangyu Zhou 1 Meifang Tang 1 Junjie Qin 1 Tong Wang 1 Shuijian Feng 1 Guohong Li 1 Huasang 1 Jiangbai Luosang 1 Wei Wang 1 Fang Chen 1 Yading Wang 1 Xiaoguang Zheng 1 2 Zhuo Li 1 Zhuoma Bianba 10 Ge Yang 10 Xinping Wang 11 Shuhui Tang 11 Guoyi Gao 12 Yong Chen 5 Zhen Luo 5 Lamu Gusang 5 Zheng Cao 1 Qinghui Zhang 1 Weihan Ouyang 1 Xiaoli Ren 1 Huiqing Liang 1 Huisong Zheng 1 Yebo Huang 1 Jingxiang Li 1 Lars Bolund 1 Karsten Kristiansen 1 7 Yingrui Li 1 Yong Zhang 1 Xiuqing Zhang 1 Ruiqiang Li 1 7 Songgang Li 1 Huanming Yang 1 Rasmus Nielsen 1 3 7 Jun Wang 1 7 Jian Wang1 Residents of the Tibetan Plateau show heritable adaptations to extreme altitude We sequenced 50 exomes of ethnic Tibetans encompassing coding sequences of 92 of human genes with an average coverage of 18 per individual Genes showing population specific allele frequency changes which represent strong candidates for altitude adaptation were identified The strongest signal of natural selection came from endothelial Per Arnt Sim PAS domain protein 1 EPAS1 a transcription factor involved in response to hypoxia One single nucleotide polymorphism SNP at EPAS1 shows a 78 frequency difference between Tibetan and Han samples representing the fastest allele frequency change observed at any human gene to date This SNP s association with erythrocyte abundance supports the role of EPAS1 in adaptation to hypoxia Thus a population genomic survey has revealed a functionally important locus in genetic adaptation to high altitude The expansion of humans into a vast range of environments may have involved both cultural and genetic adaptation Among the most severe environmental challenges to confront human populations is the low oxygen availability of high altitude regions such as the Tibetan Plateau Many residents of this region 1BGI Shenzhen Shenzhen 518083 China 2The Graduate Uni versity of Chinese Academy of Sciences Beijing 100062 China 3Department of Integrative Biology and Department of Statis tics University of California Berkeley Berkeley CA 94820 USA 4Innovative Program for Undergraduate Students School of Bioscience and Biotechnology South China University of Technology Guangzhou 510641 China 5The People s Hospital of the Tibet Autonomous Region Lhasa 850000 China 6Department of Evolution and Ecology University of California Davis Davis CA 95616 USA 7Depart ment of Biology University of Copenhagen DK 1165 Copenha gen Denmark 8Innovative Program for Undergraduate Students School …