Sequencing of 50 human exomes reveals adaptation to high altitude

Xin Yi; Yu Liang; Emilia Huerta-Sanchez; Xin Jin; Zha Xi Ping Cuo; John E Pool; Xun Xu; Hui Jiang; Nicolas Vinckenbosch; Thorfinn Sand Korneliussen; Hancheng Zheng; Tao Liu; Weiming He; Kui Li; Ruibang Luo; Xifang Nie; Honglong Wu; Meiru Zhao; Hongzhi Cao; Jing Zou; Ying Shan; Shuzheng Li; Qi Yang; George Asan; Peixiang Ni; Geng Tian; Junming Xu; Xiao Liu; Tao Jiang; Renhua Wu; Guangyu Zhou; Meifang Tang; Junjie Qin; Tong Wang; Shuijian Feng; Guohong Li; George Huasang; Jiangbai Luosang; Wei Wang; Fang Chen; Yading Wang; Xiaoguang Zheng; Zhuo Li; Zhuoma Bianba; Ge Yang; Xinping Wang; Shuhui Tang; Guoyi Gao; Chen Yong; Zhen Luo; Lamu Gusang; Zheng Cao; Qinghui Zhang; Weihan Ouyang; Xiaoli Ren; Huiqing Liang; Huisong Zheng; Yebo Huang; Jingxiang Li; Lars Bolund; Karsten Kristiansen; Yingrui Li; Yong Zhang; Xiuqing Zhang; Ruiqiang Li; Songgang Li; Huanming Yang; Rasmus Nielsen; Jun Wang; Jian Wang

doi:10.1126/science.1190371

Sequencing of 50 human exomes reveals adaptation to high altitude

Xin Yi, Yu Liang, Emilia Huerta-Sanchez, Xin Jin, Zha Xi Ping Cuo, John E Pool, Xun Xu, Hui Jiang, Nicolas Vinckenbosch, Thorfinn Sand Korneliussen, Hancheng Zheng, Tao Liu, Weiming He, Kui Li, Ruibang Luo, Xifang Nie, Honglong Wu, Meiru Zhao, Hongzhi Cao, Jing ZouYing Shan, Shuzheng Li, Qi Yang, George Asan, Peixiang Ni, Geng Tian, Junming Xu, Xiao Liu, Tao Jiang, Renhua Wu, Guangyu Zhou, Meifang Tang, Junjie Qin, Tong Wang, Shuijian Feng, Guohong Li, George Huasang, Jiangbai Luosang, Wei Wang, Fang Chen, Yading Wang, Xiaoguang Zheng, Zhuo Li, Zhuoma Bianba, Ge Yang, Xinping Wang, Shuhui Tang, Guoyi Gao, Chen Yong, Zhen Luo, Lamu Gusang, Zheng Cao, Qinghui Zhang, Weihan Ouyang, Xiaoli Ren, Huiqing Liang, Huisong Zheng, Yebo Huang, Jingxiang Li, Lars Bolund, Karsten Kristiansen, Yingrui Li, Yong Zhang, Xiuqing Zhang, Ruiqiang Li, Songgang Li, Huanming Yang, Rasmus Nielsen, Jun Wang, Jian Wang

Research output: Contribution to journal › Journal article › Research › peer-review

1197 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Science
Volume	329
Issue number	5987
Pages (from-to)	75-8
Number of pages	4
ISSN	0036-8075
DOIs	https://doi.org/10.1126/science.1190371
Publication status	Published - 2 Jul 2010

Keywords

Acclimatization
Altitude
Asian Continental Ancestry Group
Basic Helix-Loop-Helix Transcription Factors
Bayes Theorem
China
Erythrocyte Count
Ethnic Groups
Exons
Female
Gene Frequency
Genetic Association Studies
Genome, Human
Hemoglobins
Humans
Male
Oxygen
Polymorphism, Single Nucleotide
Selection, Genetic
Sequence Analysis, DNA
Tibet

Access to Document

10.1126/science.1190371

Cite this

Sequencing of 50 human exomes reveals adaptation to high altitude. / Yi, Xin; Liang, Yu; Huerta-Sanchez, Emilia; Jin, Xin; Cuo, Zha Xi Ping; Pool, John E; Xu, Xun; Jiang, Hui; Vinckenbosch, Nicolas; Korneliussen, Thorfinn Sand; Zheng, Hancheng; Liu, Tao; He, Weiming; Li, Kui; Luo, Ruibang; Nie, Xifang; Wu, Honglong; Zhao, Meiru; Cao, Hongzhi; Zou, Jing; Shan, Ying; Li, Shuzheng; Yang, Qi; Asan, George; Ni, Peixiang; Tian, Geng; Xu, Junming; Liu, Xiao; Jiang, Tao; Wu, Renhua; Zhou, Guangyu; Tang, Meifang; Qin, Junjie; Wang, Tong; Feng, Shuijian; Li, Guohong; Huasang, George; Luosang, Jiangbai; Wang, Wei; Chen, Fang; Wang, Yading; Zheng, Xiaoguang; Li, Zhuo; Bianba, Zhuoma; Yang, Ge; Wang, Xinping; Tang, Shuhui; Gao, Guoyi; Yong, Chen; Luo, Zhen; Gusang, Lamu; Cao, Zheng; Zhang, Qinghui; Ouyang, Weihan; Ren, Xiaoli; Liang, Huiqing; Zheng, Huisong; Huang, Yebo; Li, Jingxiang; Bolund, Lars; Kristiansen, Karsten; Li, Yingrui; Zhang, Yong; Zhang, Xiuqing; Li, Ruiqiang; Li, Songgang; Yang, Huanming; Nielsen, Rasmus; Wang, Jun; Wang, Jian.

In: Science, Vol. 329, No. 5987, 02.07.2010, p. 75-8.

Research output: Contribution to journal › Journal article › Research › peer-review

Yi, X, Liang, Y, Huerta-Sanchez, E, Jin, X, Cuo, ZXP, Pool, JE, Xu, X, Jiang, H, Vinckenbosch, N, Korneliussen, TS, Zheng, H, Liu, T, He, W, Li, K, Luo, R, Nie, X, Wu, H, Zhao, M, Cao, H, Zou, J, Shan, Y, Li, S, Yang, Q, Asan, G, Ni, P, Tian, G, Xu, J, Liu, X, Jiang, T, Wu, R, Zhou, G, Tang, M, Qin, J, Wang, T, Feng, S, Li, G, Huasang, G, Luosang, J, Wang, W, Chen, F, Wang, Y, Zheng, X, Li, Z, Bianba, Z, Yang, G, Wang, X, Tang, S, Gao, G, Yong, C, Luo, Z, Gusang, L, Cao, Z, Zhang, Q, Ouyang, W, Ren, X, Liang, H, Zheng, H, Huang, Y, Li, J, Bolund, L, Kristiansen, K, Li, Y, Zhang, Y, Zhang, X, Li, R, Li, S, Yang, H, Nielsen, R, Wang, J & Wang, J 2010, 'Sequencing of 50 human exomes reveals adaptation to high altitude', Science, vol. 329, no. 5987, pp. 75-8. https://doi.org/10.1126/science.1190371

Yi, Xin ; Liang, Yu ; Huerta-Sanchez, Emilia ; Jin, Xin ; Cuo, Zha Xi Ping ; Pool, John E ; Xu, Xun ; Jiang, Hui ; Vinckenbosch, Nicolas ; Korneliussen, Thorfinn Sand ; Zheng, Hancheng ; Liu, Tao ; He, Weiming ; Li, Kui ; Luo, Ruibang ; Nie, Xifang ; Wu, Honglong ; Zhao, Meiru ; Cao, Hongzhi ; Zou, Jing ; Shan, Ying ; Li, Shuzheng ; Yang, Qi ; Asan, George ; Ni, Peixiang ; Tian, Geng ; Xu, Junming ; Liu, Xiao ; Jiang, Tao ; Wu, Renhua ; Zhou, Guangyu ; Tang, Meifang ; Qin, Junjie ; Wang, Tong ; Feng, Shuijian ; Li, Guohong ; Huasang, George ; Luosang, Jiangbai ; Wang, Wei ; Chen, Fang ; Wang, Yading ; Zheng, Xiaoguang ; Li, Zhuo ; Bianba, Zhuoma ; Yang, Ge ; Wang, Xinping ; Tang, Shuhui ; Gao, Guoyi ; Yong, Chen ; Luo, Zhen ; Gusang, Lamu ; Cao, Zheng ; Zhang, Qinghui ; Ouyang, Weihan ; Ren, Xiaoli ; Liang, Huiqing ; Zheng, Huisong ; Huang, Yebo ; Li, Jingxiang ; Bolund, Lars ; Kristiansen, Karsten ; Li, Yingrui ; Zhang, Yong ; Zhang, Xiuqing ; Li, Ruiqiang ; Li, Songgang ; Yang, Huanming ; Nielsen, Rasmus ; Wang, Jun ; Wang, Jian. / Sequencing of 50 human exomes reveals adaptation to high altitude. In: Science. 2010 ; Vol. 329, No. 5987. pp. 75-8.

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title = "Sequencing of 50 human exomes reveals adaptation to high altitude",

abstract = "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.",

keywords = "Acclimatization, Altitude, Asian Continental Ancestry Group, Basic Helix-Loop-Helix Transcription Factors, Bayes Theorem, China, Erythrocyte Count, Ethnic Groups, Exons, Female, Gene Frequency, Genetic Association Studies, Genome, Human, Hemoglobins, Humans, Male, Oxygen, Polymorphism, Single Nucleotide, Selection, Genetic, Sequence Analysis, DNA, Tibet",

author = "Xin Yi and Yu Liang and Emilia Huerta-Sanchez and Xin Jin and Cuo, {Zha Xi Ping} and Pool, {John E} and Xun Xu and Hui Jiang and Nicolas Vinckenbosch and Korneliussen, {Thorfinn Sand} and Hancheng Zheng and Tao Liu and Weiming He and Kui Li and Ruibang Luo and Xifang Nie and Honglong Wu and Meiru Zhao and Hongzhi Cao and Jing Zou and Ying Shan and Shuzheng Li and Qi Yang and George Asan and Peixiang Ni and Geng Tian and Junming Xu and Xiao Liu and Tao Jiang and Renhua Wu and Guangyu Zhou and Meifang Tang and Junjie Qin and Tong Wang and Shuijian Feng and Guohong Li and George Huasang and Jiangbai Luosang and Wei Wang and Fang Chen and Yading Wang and Xiaoguang Zheng and Zhuo Li and Zhuoma Bianba and Ge Yang and Xinping Wang and Shuhui Tang and Guoyi Gao and Chen Yong and Zhen Luo and Lamu Gusang and Zheng Cao and Qinghui Zhang and Weihan Ouyang and Xiaoli Ren and Huiqing Liang and Huisong Zheng and Yebo Huang and Jingxiang Li and Lars Bolund and Karsten Kristiansen and Yingrui Li and Yong Zhang and Xiuqing Zhang and Ruiqiang Li and Songgang Li and Huanming Yang and Rasmus Nielsen and Jun Wang and Jian Wang",

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AU - Liang, Yu

AU - Huerta-Sanchez, Emilia

AU - Jin, Xin

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AU - Pool, John E

AU - Xu, Xun

AU - Jiang, Hui

AU - Vinckenbosch, Nicolas

AU - Korneliussen, Thorfinn Sand

AU - Zheng, Hancheng

AU - Liu, Tao

AU - He, Weiming

AU - Li, Kui

AU - Luo, Ruibang

AU - Nie, Xifang

AU - Wu, Honglong

AU - Zhao, Meiru

AU - Cao, Hongzhi

AU - Zou, Jing

AU - Shan, Ying

AU - Li, Shuzheng

AU - Yang, Qi

AU - Asan, George

AU - Ni, Peixiang

AU - Tian, Geng

AU - Xu, Junming

AU - Liu, Xiao

AU - Jiang, Tao

AU - Wu, Renhua

AU - Zhou, Guangyu

AU - Tang, Meifang

AU - Qin, Junjie

AU - Wang, Tong

AU - Feng, Shuijian

AU - Li, Guohong

AU - Huasang, George

AU - Luosang, Jiangbai

AU - Wang, Wei

AU - Chen, Fang

AU - Wang, Yading

AU - Zheng, Xiaoguang

AU - Li, Zhuo

AU - Bianba, Zhuoma

AU - Yang, Ge

AU - Wang, Xinping

AU - Tang, Shuhui

AU - Gao, Guoyi

AU - Yong, Chen

AU - Luo, Zhen

AU - Gusang, Lamu

AU - Cao, Zheng

AU - Zhang, Qinghui

AU - Ouyang, Weihan

AU - Ren, Xiaoli

AU - Liang, Huiqing

AU - Zheng, Huisong

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AU - Li, Jingxiang

AU - Bolund, Lars

AU - Kristiansen, Karsten

AU - Li, Yingrui

AU - Zhang, Yong

AU - Zhang, Xiuqing

AU - Li, Ruiqiang

AU - Li, Songgang

AU - Yang, Huanming

AU - Nielsen, Rasmus

AU - Wang, Jun

AU - Wang, Jian

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N2 - 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.

AB - 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.

KW - Acclimatization

KW - Altitude

KW - Asian Continental Ancestry Group

KW - Basic Helix-Loop-Helix Transcription Factors

KW - Bayes Theorem

KW - China

KW - Erythrocyte Count

KW - Ethnic Groups

KW - Exons

KW - Female

KW - Gene Frequency

KW - Genetic Association Studies

KW - Genome, Human

KW - Hemoglobins

KW - Humans

KW - Male

KW - Oxygen

KW - Polymorphism, Single Nucleotide

KW - Selection, Genetic

KW - Sequence Analysis, DNA

KW - Tibet

U2 - 10.1126/science.1190371

DO - 10.1126/science.1190371

M3 - Journal article

C2 - 20595611

VL - 329

SP - 75

EP - 78

JO - Science

JF - Science

SN - 0036-8075

IS - 5987

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