Whole genome sequencing of six dog breeds from continuous altitudes reveals adaption to high-altitude hypoxia

  1. Yixue Li2
  1. 1 Yunnan Agricultural University;
  2. 2 Shanghai Institutes for Biological Sciences;
  3. 3 China Agricultural University;
  4. 4 Shanghai Center for Bioinformation Technology, Shanghai Industrial Technology Institute;
  5. 5 EG Information Technology Enterprise (EGI), Encode Genomics Biotechnology Co., Ltd.;
  6. 6 Northwest Agricultural and Forestry University;
  7. 7 National Facility for Protein Science in Shanghai
  1. * Corresponding author; email: zwang01{at}sibs.ac.cn

Abstract

The hypoxic environment imposes severe selective pressure on species living at high altitude. To understand the genetic bases of adaption to high altitude in dogs, we performed whole-genome sequencing of 60 dogs including five breeds living at continuous altitudes along the Tibetan plateau from 800 to 5,100 m as well as one European breed. More than 150x sequencing coverage for each breed provides us a comprehensive assessment of the genetic polymorphisms of the dogs including Tibetan Mastiffs. Comparison of the breeds from different altitudes reveals strong signals of population differentiation at the locus of hypoxia-related genes including endothelial Per-Arnt-Sim (PAS) domain protein 1 (EPAS1) and beta hemoglobin cluster. Especially, four novel non-synonymous mutations specific to high-altitude dogs are identified at EPAS1, one of which occurred at a quite conserved site in the PAS domain. The association testing between EPAS1 genotypes and blood-related phenotypes on additional high-altitude dogs reveals that the homozygous mutation is associated with the decreased blood flow resistance, which may help to improve hemorheologic fitness. Interestingly, EPAS1 was also identified as a selective target in Tibetan highlanders, though no amino acid changes were found. Thus, our results not only indicate parallel evolution of humans and dogs in adaption to high-altitude hypoxia, but also provide a new opportunity to study the role of EPAS1 in the adaptive processes.

  • Received December 30, 2013.
  • Accepted April 8, 2014.

This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.

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  1. Genome Res. gr.171876.113 Published by Cold Spring Harbor Laboratory Press

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