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A single mutation underlying phenotypic convergence for hypoxia adaptation on the Qinghai-Tibetan Plateau

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Fig. 1: Substitution of a parallel amino acid of RETSAT among QTP mammals endows mice with convergent phenotypes and enhanced hypoxia tolerance.

Data availability

The raw sequence data reported in this study have been deposited in the Genome Sequence Archive in BIG Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences (accession numbers CRA000080, CRA000079). They are publicly accessible at The assemblies for the plateau zokor and plateau pika have been deposited in the BIG Genome Warehouse (GWH) under project numbers GWHABJY00000000 and GWHABJX00000000. The RETSAT protein sequence alignment across 137 mammals has been uploaded to the Dryad Digital Repository (doi:10.5061/dryad.ttdz08kxg).


  1. Storz, J. F. et al. J. Exp. Biol. 213, 4125–4136 (2010).

    Article  Google Scholar 

  2. Qi, X. et al. Acta Physiol. Sin. 60, 348–354 (2008).

    CAS  Google Scholar 

  3. Rong, C. et al. Am. J. Vet. Res. 73, 809–813 (2012).

    Article  Google Scholar 

  4. Anand, I. et al. Thorax 41, 696–700 (1986).

    CAS  Article  Google Scholar 

  5. Qiu, Q. et al. Nat. Genet. 44, 946–949 (2012).

    CAS  Article  Google Scholar 

  6. Ge, R. L. et al. Nat. Commun. 4, 1858 (2013).

    Article  Google Scholar 

  7. Liu, Z. et al. Sci. Adv. 4, eaat8821 (2018).

    CAS  Article  Google Scholar 

  8. Moise, A. R. et al. J. Biol. Chem. 279, 50230–50242 (2004).

    CAS  Article  Google Scholar 

  9. Moise, A. R. et al. Mol. Pharmacol. 76, 1228–1237 (2009).

    CAS  Article  Google Scholar 

  10. Pang, X. Y. et al. Arch. Biochem. Biophys. 633, 93–102 (2017).

    CAS  Article  Google Scholar 

  11. Zou, Z. et al. Mol. Biol. Evol. 32, 2085–2096 (2015).

    CAS  Article  Google Scholar 

  12. Thomas, G. W. et al. Genome Biol. Evol. 9, 213–221 (2017).

    PubMed  PubMed Central  Google Scholar 

  13. Lee, J. H. et al. Sci. Adv. 4, eaat9660 (2018).

    Article  Google Scholar 

  14. Meijler, F. L. et al. Heart Rhythm. 2, 188–196 (2005).

    Article  Google Scholar 

  15. Crile, G. C. et al. Ohio J. Sci. 40, 219–259 (1939).

    Google Scholar 

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We thank Zhengting Zou for modifying the computational program of convCalScript and Zhong-Ru Gu for his advice in genome assembly. This work was supported jointly and equally by the Second Tibetan Plateau Scientific Expedition and Research Program (2019QZKK0501) and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB13020400). This work was also supported by the National Natural Science Foundation of China (U1902216, 81772996, 81672764, 31621062, 31871270, 31922010, 31871277, 3190013), Science and Technology Department of Qinghai Province (Sanjiangyuan National Park Animal Genome Program), and Yunnan Applied Basic Research Projects (2016FA009, 2019FJ009). C.Y., S.P. and Z.L. were also supported by the Youth Innovation Promotion Association, CAS, and the Youth Talent Support Program of Yunnan Province (2019FI008).

Author information




P.S., Y.C., and X.-J.Z. designed and supervised the project. P.S. coordinated the project. X.-J.Z. led the genome assembly group. Y.C. led the functional experiment group. P.S. led the evolutionary genome analysis group. T.-Z.Z. collected samples. D.X., S.P., and X.-J.Z. performed genome assembly and annotation. D.X., Z.L., H.Y., T.Z., Y.G., P.C., and P.S. analyzed genomic data. C.Y., Q.S., X.Z., M.L., and Y.C. performed functional experiments. D.X., Z.L., Y.C., C.Y., X.-J.Z., and P.S. wrote the manuscript.

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Correspondence to Xiangjiang Zhan, Yongbin Chen or Peng Shi.

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The authors declare no competing interests.

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Xu, D., Yang, C., Shen, Q. et al. A single mutation underlying phenotypic convergence for hypoxia adaptation on the Qinghai-Tibetan Plateau. Cell Res 31, 1032–1035 (2021).

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