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

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Abstract

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 (SaO2) and blood platelet count, respectively, at the EDAR locus. Among these, rs10865026 and rs3749110 (associated with SaO2 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.

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Acknowledgements

We thank all of the Tibetan volunteers who donated samples. This work was supported by the National Natural Science Foundation of China (91131905, 30890030), Strategic Priority Research Program of the Chinese Academy of Sciences (XDB13020500), and Weng Hongwu Original Scientific Research Foundation, Peking University. M.S. Raza was partially sponsored by UCAS fellowship program and supported by the CAS-TWAS president’s fellowship program for international doctoral candidates.

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Authors and Affiliations

  1. CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China

    Jianming Shao, Muhammad Sohail Raza & Changqing Zeng

  2. University of Chinese Academy of Sciences, Beijing, 100049, China

    Jianming Shao, Muhammad Sohail Raza & Changqing Zeng

  3. The Innovation Center of Excellence on Science and Education of Life Sciences, Chinese Academy of Sciences, Beijing, 100049, China

    Changqing Zeng

  4. Collaborative Innovation Center of Genetics and Development, Shanghai, 200438, China

    Changqing Zeng

  5. Medical College of Tibet University, Lhasa, 850002, China

    Basang Zhuoma

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  1. Jianming Shao
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  3. Basang Zhuoma
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Correspondence to Changqing Zeng.

Electronic supplementary material

Figure S1

Chromosome state of EDAR region harboring rs10865026. Red line marks the location of candidate variant.

Table S1 Sample information in resequencing

Table S2 EDAR SNPs with Tibetan-Han Fst>0.2

Table S3Fst values of QTA-SNPs between low and high altitude Peruvians

Table S4 Genotype frequency comparison of rs10865026

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Shao, J., Raza, M.S., Zhuoma, B. et al. Evolutionary significance of selected EDAR variants in Tibetan high-altitude adaptations. Sci. China Life Sci. 61, 68–78 (2018). https://doi.org/10.1007/s11427-016-9045-7

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