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Science 329 (5987): 72-75

Copyright © 2010 by the American Association for the Advancement of Science

Genetic Evidence for High-Altitude Adaptation in Tibet

Tatum S. Simonson,1 Yingzhong Yang,2,* Chad D. Huff,1 Haixia Yun,2,* Ga Qin,2,* David J. Witherspoon,1 Zhenzhong Bai,2,* Felipe R. Lorenzo,3 Jinchuan Xing,1 Lynn B. Jorde,1,{dagger} Josef T. Prchal,1,3,{dagger} RiLi Ge2,*,{dagger}

Abstract: Tibetans have lived at very high altitudes for thousands of years, and they have a distinctive suite of physiological traits that enable them to tolerate environmental hypoxia. These phenotypes are clearly the result of adaptation to this environment, but their genetic basis remains unknown. We report genome-wide scans that reveal positive selection in several regions that contain genes whose products are likely involved in high-altitude adaptation. Positively selected haplotypes of EGLN1 and PPARA were significantly associated with the decreased hemoglobin phenotype that is unique to this highland population. Identification of these genes provides support for previously hypothesized mechanisms of high-altitude adaptation and illuminates the complexity of hypoxia-response pathways in humans.

1 Eccles Institute of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
2 Research Center for High-Altitude Medicine, Qinghai University Medical School, Xining, Qinghai 810001, People’s Republic of China.
3 Division of Hematology and Department of Pathology (ARUP), University of Utah School of Medicine and VAH, Salt Lake City, UT 84112, USA.

* The Research Center for High-Altitude Medicine initiated the research project and was primarily responsible for phenotyping and DNA collection.

{dagger} To whom correspondence should be addressed. E-mail: lbj{at}genetics.utah.edu (L.B.J); josef.prchal{at}hsc.utah.edu (J.T.P.); geriligao{at}hotmail.com (R.L.G.)

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