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Genome Res. 2014 Aug;24(8):1308-15. doi: 10.1101/gr.171876.113. Epub 2014 Apr 10.

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

Author information

1
College of Animal Science and Technology, Yunnan Agricultural University, Kunming 650201, China; College of Animal Science and Technology/State Key Laboratory for Agrobiotechnology, China Agricultural University, Beijing 100094, China;
2
Key Laboratory of Systems Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Shanghai Center for Bioinformation Technology, Shanghai Industrial Technology Institute, Shanghai 201203, China;
3
College of Animal Science and Technology/State Key Laboratory for Agrobiotechnology, China Agricultural University, Beijing 100094, China;
4
Shanghai Center for Bioinformation Technology, Shanghai Industrial Technology Institute, Shanghai 201203, China; EG Information Technology Enterprise (EGI), Encode Genomics Biotechnology Co., Ltd., Shanghai 200235, China;
5
EG Information Technology Enterprise (EGI), Encode Genomics Biotechnology Co., Ltd., Shanghai 200235, China;
6
College of Animal Science and Technology, Yunnan Agricultural University, Kunming 650201, China;
7
Shanghai Center for Bioinformation Technology, Shanghai Industrial Technology Institute, Shanghai 201203, China;
8
College of Animal Science and Technology, Northwest Agricultural and Forestry University, Yangling 712100, China;
9
Shanghai Center for Bioinformation Technology, Shanghai Industrial Technology Institute, Shanghai 201203, China; School of Life Science and Technology, Shanghai Jiaotong University, Shanghai 200240, China;
10
National Center for Protein Science Shanghai, National Facility for Protein Science in Shanghai, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China;
11
Key Laboratory of Systems Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; Shanghai Center for Bioinformation Technology, Shanghai Industrial Technology Institute, Shanghai 201203, China; School of Life Science and Technology, Shanghai Jiaotong University, Shanghai 200240, China; School of Life Science and Technology, Shanghai Tongji University, Shanghai 200092, China.

Abstract

The hypoxic environment imposes severe selective pressure on species living at high altitude. To understand the genetic bases of adaptation 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 5100 m as well as one European breed. More than 150× sequencing coverage for each breed provides us with 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. Notably, four novel nonsynonymous 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 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 adaptation to high-altitude hypoxia, but also provide a new opportunity to study the role of EPAS1 in the adaptive processes.

PMID:
24721644
PMCID:
PMC4120084
DOI:
10.1101/gr.171876.113
[Indexed for MEDLINE]
Free PMC Article
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