Article

Admixture facilitates genetic adaptations to high altitude in Tibet

  • Nature Communications 5, Article number: 3281 (2014)
  • doi:10.1038/ncomms4281
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Abstract

Admixture is recognized as a widespread feature of human populations, renewing interest in the possibility that genetic exchange can facilitate adaptations to new environments. Studies of Tibetans revealed candidates for high-altitude adaptations in the EGLN1 and EPAS1 genes, associated with lower haemoglobin concentration. However, the history of these variants or that of Tibetans remains poorly understood. Here we analyse genotype data for the Nepalese Sherpa, and find that Tibetans are a mixture of ancestral populations related to the Sherpa and Han Chinese. EGLN1 and EPAS1 genes show a striking enrichment of high-altitude ancestry in the Tibetan genome, indicating that migrants from low altitude acquired adaptive alleles from the highlanders. Accordingly, the Sherpa and Tibetans share adaptive haemoglobin traits. This admixture-mediated adaptation shares important features with adaptive introgression. Therefore, we identify a novel mechanism, beyond selection on new mutations or on standing variation, through which populations can adapt to local environments.

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Acknowledgements

We thank Sherpa participants in this study for providing their phenotype data and genetic material. We also thank the Genomics Core Facility of the Department of Genetics and Genomics and the Case Comprehensive Cancer Center, Case Western Reserve University, for providing their genotyping services. We are grateful to D. Reich, N. Patterson, P. Moorjani, J. Novembre, S. Gopalakrishnan, M. Kronforst, R. Hudson, M. Przeworski and M. Aldenderfer for helpful discussions and advice on data analysis methods. This work was supported in part by the National Science Foundation Grant BCS-0924726. C.J. was supported by Samsung Scholarship.

Author information

Author notes

    • Jonathan K. Pritchard

    Present address: Departments of Genetics and Biology, Stanford University, Stanford, California 94305-5020, USA

Affiliations

  1. Department of Human Genetics, University of Chicago, Chicago, Illinois 60637, USA

    • Choongwon Jeong
    • , Gorka Alkorta-Aranburu
    • , David B. Witonsky
    • , Jonathan K. Pritchard
    •  & Anna Di Rienzo
  2. Oxford University Clinical Research Unit, Patan Hospital, Lal Durbar marg, GPO Box 3596, Kathmandu, Nepal

    • Buddha Basnyat
  3. Mountain Medicine Society of Nepal, Maharajgunj, Kathmandu, Nepal

    • Maniraj Neupane
  4. Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA

    • Jonathan K. Pritchard
  5. Department of Anthropology, Case Western Reserve University, Cleveland, Ohio 44106-7125, USA

    • Cynthia M. Beall

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Contributions

C.M.B. and A.D. conceived the project. B.B., M.N. and C.M.B. recruited the study subjects and collected phenotype data and genetic material. C.J., G.A.-A. and D.B.W. performed statistical data analyses. J.K.P. provided advice on data analysis methods. C.J. and A.D.R. wrote the paper with input from all the co-authors.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Anna Di Rienzo.

Supplementary information

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    Supplementary Information

    Supplementary Figures 1-14 and Supplementary Tables 1-17

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