Sequencing of 50 Human Exomes Reveals Adaptation to High Altitude

被引：1179

作者：

Yi, Xin ^{[1
,2
]}

Liang, Yu ^{[1
,2
]}

Huerta-Sanchez, Emilia ^{[3
,4
]}

Jin, Xin ^{[1
,5
]}

Cuo, Zha Xi Ping ^{[2
,6
]}

Pool, John E. ^{[3
,4
,7
]}

Xu, Xun ^{[1
]}

Jiang, Hui ^{[1
]}

Vinckenbosch, Nicolas ^{[3
,4
]}

Korneliussen, Thorfinn Sand ^{[8
]}

Zheng, Hancheng ^{[1
,5
]}

Liu, Tao ^{[1
]}

He, Weiming ^{[1
,9
]}

Li, Kui ^{[2
,6
]}

Luo, Ruibang ^{[1
,5
]}

Nie, Xifang ^{[1
]}

Wu, Honglong ^{[1
,10
]}

Zhao, Meiru ^{[1
]}

Cao, Hongzhi ^{[1
,10
]}

Zou, Jing ^{[1
]}

Shan, Ying ^{[1
,5
]}

Li, Shuzheng ^{[1
]}

Yang, Qi ^{[1
]}

Asan ^{[1
]}

Ni, Peixiang ^{[1
]}

Tian, Geng ^{[1
,2
]}

Xu, Junming ^{[1
]}

Liu, Xiao ^{[1
]}

Jiang, Tao ^{[1
,10
]}

Wu, Renhua ^{[1
]}

Zhou, Guangyu ^{[1
]}

Tang, Meifang ^{[1
]}

Qin, Junjie ^{[1
]}

Wang, Tong ^{[1
]}

Feng, Shuijian ^{[1
]}

Li, Guohong ^{[1
]}

Huasang ^{[1
]}

Luosang, Jiangbai ^{[1
]}

Wang, Wei ^{[1
]}

Chen, Fang ^{[1
]}

Wang, Yading ^{[1
]}

Zheng, Xiaoguang ^{[1
,2
]}

Li, Zhuo ^{[1
]}

Bianba, Zhuoma ^{[11
]}

Yang, Ge ^{[11
]}

Wang, Xinping ^{[12
]}

Tang, Shuhui ^{[12
]}

Gao, Guoyi ^{[13
]}

Chen, Yong ^{[6
]}

Luo, Zhen ^{[6
]}

机构：

[1] BGI Shenzhen, Shenzhen 518083, Peoples R China

[2] Chinese Acad Sci, Grad Univ, Beijing 100062, Peoples R China

[3] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94820 USA

[4] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94820 USA

[5] S China Univ Technol, Innovat Program Undergrad Students, Sch Biosci & Biotechnol, Guangzhou 510641, Guangdong, Peoples R China

[6] Peoples Hosp Tibet Autonomous Reg, Lhasa 850000, Peoples R China

[7] Univ Calif Davis, Dept Ecol & Evolut, Davis, CA 95616 USA

[8] Univ Copenhagen, Dept Biol, DK-1165 Copenhagen, Denmark

[9] S China Univ Technol, Sch Sci, Innovat Program Undergrad Students, Guangzhou 510641, Guangdong, Peoples R China

[10] Shenzhen Univ, Genome Res Inst, Sch Med, Shenzhen 518060, Peoples R China

[11] Peoples Hosp Lhasa, Lhasa 850000, Peoples R China

[12] Mil Gen Hosp Tibet, Lhasa 850007, Peoples R China

[13] Hosp XiShuangBanNa Dai Nationalities, Autonomous Jinghong 666100, Yunnan, Peoples R China

来源：

SCIENCE | 2010年 / 329卷 / 5987期

基金：

美国国家科学基金会; 中国国家自然科学基金; 瑞士国家科学基金会;

关键词：

HEMOGLOBIN LEVELS; POINT MUTATIONS; GENE; TIBETAN; ASSOCIATION; HIF-1-ALPHA; SELECTION; LHASA; LOCI;

D O I：

10.1126/science.1190371

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 18x 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.

引用

页码：75 / 78

页数：4

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