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Front. Physiol. | doi: 10.3389/fphys.2019.01116

Population history and altitude-related adaptation in the Sherpa

 Sushil Bhandari1* and Gianpiero L. Cavalleri1*
  • 1Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Ireland

The first ascent of Mount Everest by Tenzing Norgay and Sir Edmund Hillary in 1953 brought global attention to the Sherpa people and human performance at altitude. The Sherpa inhabit the Khumbu Valley of Nepal, and are descendants of a population that has resided continuously on the Tibetan plateau for the past ~25,000 to 40,000 years. The long exposure of the Sherpa to an inhospitable environment has driven genetic selection and produced distinct adaptive phenotypes. This review summarizes the population history of the Sherpa and their physiological and genetic adaptation to hypoxia. Genome-wide studies have identified robust signals of positive selection across EPAS1, EGLN1 and PPARA, that are associated with hemoglobin levels, which likely protect the Sherpa from altitude sickness. However, the biological underpinnings of other adaptive phenotypes such as birth weight and the increased reproductive success of Sherpa women are unknown. Further studies are required to identify additional signatures of selection and refine existing Sherpa-specific adaptive phenotypes to understand how genetic factors have underpinned adaptation in this population. By correlating known and emerging signals of genetic selection with adaptive phenotypes, we can further reveal hypoxia-related biological mechanisms of adaptation. Ultimately this work could provide valuable information regarding treatments of hypoxia-related illnesses including stroke, heart failure, lung disease and cancer.

Keywords: Sherpa climbers, High altitude adaptation, genetic selection, natural selection, Hypoxia Adaptation

Received: 30 Jan 2019; Accepted: 12 Aug 2019.

Edited by:

Tatum S. Simonson, University of California, San Diego, United States

Reviewed by:

Lorna G. Moore, School of Medicine, University of Colorado Denver, United States
Cynthia M. Beall, Case Western Reserve University, United States
Edward Gilbert-Kawai, University College London, United Kingdom  

Copyright: © 2019 Bhandari and Cavalleri. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Sushil Bhandari, Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, County Dublin, Ireland, sushilbhandari@rcsi.ie
Prof. Gianpiero L. Cavalleri, Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, County Dublin, Ireland, gcavalleri@rcsi.ie