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Sequencing of 50 Human Exomes Reveals Adaptation to High Altitude

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

in Acclimatization - genetics / Adaptation / Alleles / Altitude / Asian Continental Ancestry Group - genetics / Basic Helix-Loop-Helix Transcription Factors - genetics / Basic Helix-Loop-Helix Transcription Factors - physiology / Bayes Theorem / China / Erythrocyte Count / Erythrocytes / Ethnic Groups - genetics / Exome / Exons / Female / Gene Frequency / Genes / Genetic Association Studies / Genome, Human / Genomics / Grants / Hemoglobins - analysis / Heredity / High altitude / Human / Humans / Hypoxia / loci / Male / Minority & ethnic groups / Natural selection / Oxygen / Oxygen - blood / Polymorphism / Polymorphism, Single Nucleotide / Population genetics / Selection, Genetic / Sequence Analysis, DNA / Sequencing / single nucleotide polymorphism / surveys / Tibet / transcription factors

2010

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Sequencing of 50 Human Exomes Reveals Adaptation to High Altitude

2010

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2010

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Journal Article

Sequencing of 50 Human Exomes Reveals Adaptation to High Altitude

Li, Songgang,

Cao, Hongzhi,

Bianba, Zhuoma,

Li, Guohong,

Liu, Xiao,

Huang, Yebo,

Ouyang, Weihan,

Liang, Yu,

Cao, Zheng,

Gao, Guoyi,

Bolund, Lars,

Ren, Xiaoli,

Zheng, Hancheng,

Jiang, Tao,

Wang, Xinping,

Chen, Yong,

Nielsen, Rasmus,

Li, Jingxiang,

Yang, Huanming,

Zhang, Xiuqing,

Zhao, Meiru,

Ni, Peixiang,

Qin, Junjie,

Yang, Ge,

Zhang, Qinghui,

Li, Kui,

Wang, Tong,

Huasang,

Pool, John E,

Tang, Meifang,

Liang, Huiqing,

Zhang, Yong,

Tang, Shuhui,

Luo, Zhen,

Wu, Honglong,

Wang, Yading,

Wang, Wei,

Zheng, Huisong,

Korneliussen, Thorfinn Sand,

Feng, Shuijian,

Xu, Xun,

Nie, Xifang,

Tian, Geng,

Li, Ruiqiang,

Xu, Junming,

Jin, Xin,

Zheng, Xiaoguang,

Gusang, Lamu,

He, Weiming,

Kristiansen, Karsten,

Luo, Ruibang,

Cuo, Zha Xi Ping,

Asan,

Vinckenbosch, Nicolas,

Shan, Ying,

Wang, Jian,

Luosang, Jiangbai,

Huerta-Sanchez, Emilia,

Jiang, Hui,

Zou, Jing,

Yi, Xin,

Zhou, Guangyu,

Wu, Renhua,

Wang, Jun,

Li, Yingrui,

Li, Shuzheng,

Li, Zhuo,

Chen, Fang,

Yang, Qi,

Liu, Tao

2010

Overview

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.

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Publisher

American Association for the Advancement of Science,The American Association for the Advancement of Science

Subject

Acclimatization - genetics

/ Adaptation

/ Alleles

/ Altitude

/ Asian Continental Ancestry Group - genetics

/ Basic Helix-Loop-Helix Transcription Factors - genetics

/ Basic Helix-Loop-Helix Transcription Factors - physiology