Whole genome sequencing of six dog breeds from continuous altitudes reveals adaption to high-altitude hypoxia
- Xiao Gou1,
- Zhen Wang2,8,
- Ning Li3,
- Feng Qiu4,
- Ze Xu5,
- Dawei Yan1,
- Shuli Yang1,
- Jia Jia4,
- Xiaoyan Kong1,
- Zehui Wei6,
- Shaoxiong Lu1,
- Linsheng Lian1,
- Changxin Wu3,
- Xueyan Wang1,
- Guozhi Li1,
- Teng Ma1,
- Qiang Jiang1,
- Xue Zhao1,
- Jiaqiang Yang1,
- Baohong Liu5,
- Dongkai Wei5,
- Hong Li2,
- Jianfa Yang1,
- Yulin Yan1,
- Guiying Zhao1,
- Xingxing Dong1,
- Mingli Li1,
- Weidong Deng1,
- Jing Leng1,
- Chaochun Wei4,
- Chuan Wang7,
- Huaming Mao1,
- Hao Zhang3,
- Guohui Ding2 and
- Yixue Li2
- 1 Yunnan Agricultural University;
- 2 Shanghai Institutes for Biological Sciences;
- 3 China Agricultural University;
- 4 Shanghai Center for Bioinformation Technology, Shanghai Industrial Technology Institute;
- 5 EG Information Technology Enterprise (EGI), Encode Genomics Biotechnology Co., Ltd.;
- 6 Northwest Agricultural and Forestry University;
- 7 National Facility for Protein Science in Shanghai
- ↵* 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.
- Published by Cold Spring Harbor Laboratory Press
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