Evolutionary significance of selected EDAR variants in Tibetan high-altitude adaptations  

作　　者：Jianming Shao Muhammad Sohail Raza Basang Zhuoma Changqing Zeng 

机构地区：[1]CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China [2]University of Chinese Academy of Sciences, Beijing 100049, China [3]The Innovation Center of Excellence on Science and Education of Life Sciences, Chinese Academy of Sciences, Beijing 100049, China [4]Collaborative Innovation Center of Genetics and Development, Shanghai 200438, China [5]Medical College of Tibet University, Lhasa 850002, China

出　　处：《Science China(Life Sciences)》2018年第1期68-78,共11页中国科学（生命科学英文版）

基　　金：supported by the National Natural Science Foundation of China (91131905, 30890030);Strategic Priority Research Program of the Chinese Academy of Sciences (XDB13020500);Weng Hongwu Original Scientific Research Foundation, Peking University

摘　　要：Humans have been exposed to many environmental challenges since their evolutionary origins in Africa and subsequent migrations to the rest of the world. A severe environmental challenge to human migrants was hypoxia caused by low barometric oxygen pressure at high altitudes. Several genome-wide scans have elucidated the genetic basis of human high-altitude adaptations.However, the dearth of functional variant information has led to the successful association of only a few candidate genes. In the present study, we employed a candidate gene approach and re-sequenced the EDAR locus in 45 Tibetan individuals to identify mutations involved in hypoxia adaptation. We identified 10 and five quantitative trait-associated mutations for oxygen saturation (SaO_2) and blood platelet count, respectively, at the EDAR locus. Among these, rs10865026 and rs3749110 (associated with SaO_2 and platelet count, respectively) were identified as functional candidate targets. These data demonstrate that EDAR has undergone natural selection in recent human history and indicate an important role of EDAR variants in Tibetan high-altitude adaptations.Humans have been exposed to many environmental challenges since their evolutionary origins in Africa and subsequent migrations to the rest of the world. A severe environmental challenge to human migrants was hypoxia caused by low barometric oxygen pressure at high altitudes. Several genome-wide scans have elucidated the genetic basis of human high-altitude adaptations.However, the dearth of functional variant information has led to the successful association of only a few candidate genes. In the present study, we employed a candidate gene approach and re-sequenced the EDAR locus in 45 Tibetan individuals to identify mutations involved in hypoxia adaptation. We identified 10 and five quantitative trait-associated mutations for oxygen saturation （SaO_2） and blood platelet count, respectively, at the EDAR locus. Among these, rs10865026 and rs3749110 （associated with SaO_2 and platelet count, respectively） were identified as functional candidate targets. These data demonstrate that EDAR has undergone natural selection in recent human history and indicate an important role of EDAR variants in Tibetan high-altitude adaptations.

关 键 词：Tibetan high altitude adaptation EDAR 

分 类 号：Q987[生物学—遗传学]