Sequencing of 50 human exomes reveals adaptation to high altitude.
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.
Yi
Xin
X
BGI-Shenzhen, Shenzhen 518083, China.
Liang
Yu
Y
Huerta-Sanchez
Emilia
E
Jin
Xin
X
Cuo
Zha Xi Ping
ZX
Pool
John E
JE
Xu
Xun
X
Jiang
Hui
H
Vinckenbosch
Nicolas
N
Korneliussen
Thorfinn Sand
TS
Zheng
Hancheng
H
Liu
Tao
T
He
Weiming
W
Li
Kui
K
Luo
Ruibang
R
Nie
Xifang
X
Wu
Honglong
H
Zhao
Meiru
M
Cao
Hongzhi
H
Zou
Jing
J
Shan
Ying
Y
Li
Shuzheng
S
Yang
Qi
Q
Asan
Ni
Peixiang
P
Tian
Geng
G
Xu
Junming
J
Liu
Xiao
X
Jiang
Tao
T
Wu
Renhua
R
Zhou
Guangyu
G
Tang
Meifang
M
Qin
Junjie
J
Wang
Tong
T
Feng
Shuijian
S
Li
Guohong
G
Huasang
Luosang
Jiangbai
J
Wang
Wei
W
Chen
Fang
F
Wang
Yading
Y
Zheng
Xiaoguang
X
Li
Zhuo
Z
Bianba
Zhuoma
Z
Yang
Ge
G
Wang
Xinping
X
Tang
Shuhui
S
Gao
Guoyi
G
Chen
Yong
Y
Luo
Zhen
Z
Gusang
Lamu
L
Cao
Zheng
Z
Zhang
Qinghui
Q
Ouyang
Weihan
W
Ren
Xiaoli
X
Liang
Huiqing
H
Zheng
Huisong
H
Huang
Yebo
Y
Li
Jingxiang
J
Bolund
Lars
L
Kristiansen
Karsten
K
Li
Yingrui
Y
Zhang
Yong
Y
Zhang
Xiuqing
X
Li
Ruiqiang
R
Li
Songgang
S
Yang
Huanming
H
Nielsen
Rasmus
R
Wang
Jun
J
Wang
Jian
J
D000064:Acclimatization / Q000235:genetics*; D000531:Altitude; D044466:Asian People / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000502:physiology; D001499:Bayes Theorem; D002681:China; D004906:Erythrocyte Count; D005006:Ethnicity / Q000235:genetics; D005091:Exons; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D015894:Genome, Human; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008297:Male; D010100:Oxygen / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D018609:Tibet; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D006454:Hemoglobins; D010100:Oxygen; D000099162:Endothelial PAS Domain-Containing Protein 1