title: Genetic convergence in the adaptation of dogs and humans to the high-altitude environment of the tibetan plateau.
abstract: The high-altitude hypoxic environment represents one of the most extreme challenges for mammals. Previous studies of humans on the Tibetan plateau and in the Andes Mountains have identified statistical signatures of selection in different sets of loci. Here, we first measured the hemoglobin levels in village dogs from Tibet and those from Chinese lowlands. We found that the hemoglobin levels are very similar between the two groups, suggesting that Tibetan dogs might share similar adaptive strategies as the Tibetan people. Through a whole-genome sequencing approach, we have identified EPAS1 and HBB as candidate genes for the hypoxic adaptation on the Tibetan plateau. The population genetic analysis shows a significant convergence between humans and dogs in Tibet. The similarities in the sets of loci that exhibit putative signatures of selection and the hemoglobin levels between humans and dogs of the same environment, but not between human populations in different regions, suggests an extraordinary landscape of convergent evolution between human beings and their best friend on the Tibetan plateau.
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, and Yunnan Laboratory of Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Wang
authors.affiliation: Laboratory for Conservation and Utilization of Bio-resources, Yunnan University, Kunming, China.
authors.forename: Ruo-Xi
authors.initials: RX
authors.lastname: Fan
authors.affiliation: Center for Computational Biology and Laboratory of Disease Genomics and Individualized Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhai
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, and Yunnan Laboratory of Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Laboratory for Conservation and Utilization of Bio-resources, Yunnan University, Kunming, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Laboratory for Conservation and Utilization of Bio-resources, Yunnan University, Kunming, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Laboratory for Conservation and Utilization of Bio-resources, Yunnan University, Kunming, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, and Yunnan Laboratory of Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China Department of Molecular and Cell Biology, School of Life Sciences, University of Science and Technology of China, Hefei, China.
authors.forename: He-Chuan
authors.initials: HC
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, and Yunnan Laboratory of Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
authors.forename: Shi-Fang
authors.initials: SF
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, and Yunnan Laboratory of Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
authors.forename: Chun-Ling
authors.initials: CL
authors.lastname: Zhu
authors.affiliation: Laboratory for Conservation and Utilization of Bio-resources, Yunnan University, Kunming, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, and Yunnan Laboratory of Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Key Laboratory for High Altitude Medicine of Ministry of Chinese Education and Research Center for High Altitude Medicine, Qinghai University, Xining, China.
authors.forename: Ri-Li
authors.initials: RL
authors.lastname: Ge
authors.affiliation: Laboratory for Conservation and Utilization of Bio-resources, Yunnan University, Kunming, China Department of Ecology and Evolution, University of Chicago.
authors.forename: Chung-I
authors.initials: CI
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, and Yunnan Laboratory of Molecular Biology of Domestic Animals, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China Laboratory for Conservation and Utilization of Bio-resources, Yunnan University, Kunming, China Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore zhangyp@mail.kiz.ac.cn.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Zhang
mesh_terms: D000064:Acclimatization; D000222:Adaptation, Physiological; D000531:Altitude; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D004285:Dogs / Q000097:blood / Q000235:genetics / Q000502:physiology*; D019143:Evolution, Molecular; D005828:Genetics, Population; D016678:Genome; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008958:Models, Molecular; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D018609:Tibet; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D006454:Hemoglobins; D000099162:Endothelial PAS Domain-Containing Protein 1
keywords: EPAS1; Tibetan village dog; convergence; high-altitude adaptation
references.citation: Bioinformatics. 2009 Jul 15;25(14):1754-60
references.pmid: 19451168
references.citation: Mol Biol Evol. 2011 Feb;28(2):1003-11
references.pmid: 20961960
references.citation: High Alt Med Biol. 2008 Summer;9(2):148-57
references.pmid: 18578646
references.citation: Vet Clin Pathol. 2004;33(1):32-8
references.pmid: 15048625
references.citation: Nature. 2005 Dec 8;438(7069):803-19
references.pmid: 16341006
references.citation: J Am Chem Soc. 2009 Dec 9;131(48):17647-54
references.pmid: 19950993
references.citation: PLoS Genet. 2010 Sep 09;6(9):e1001116
references.pmid: 20838600
references.citation: Proc Natl Acad Sci U S A. 2013 Dec 17;110(51):20669-74
references.pmid: 24297909
references.citation: Science. 1961 Jun 2;133(3466):1770-1
references.pmid: 13783042
references.citation: Nat Methods. 2010 Apr;7(4):248-9
references.pmid: 20354512
references.citation: Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11459-64
references.pmid: 20534544
references.citation: Bioinformatics. 2009 Aug 15;25(16):2078-9
references.pmid: 19505943
references.citation: Nature. 2001 May 10;411(6834):199-204
references.pmid: 11346797
references.citation: PLoS Genet. 2012;8(12):e1003110
references.pmid: 23236293
references.citation: Genome Biol. 2012 Jan 20;13(1):R1
references.pmid: 22264333
references.citation: Nat Genet. 2007 Nov;39(11):1321-8
references.pmid: 17906626
references.citation: Proc Natl Acad Sci U S A. 2007 May 15;104 Suppl 1:8655-60
references.pmid: 17494744
references.citation: Genome Res. 2002 Dec;12(12):1805-14
references.pmid: 12466284
references.citation: Science. 2010 Jul 2;329(5987):75-8
references.pmid: 20595611
references.citation: Proc Natl Acad Sci U S A. 2009 Jan 13;106(2):450-5
references.pmid: 19129502
references.citation: Compr Physiol. 2012 Apr;2(2):1463-89
references.pmid: 23798307
references.citation: Nat Commun. 2013;4:1860
references.pmid: 23673645
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14450-5
references.pmid: 19667207
references.citation: Trends Biochem Sci. 2000 Jun;25(6):300-2
references.pmid: 10838572
references.citation: Science. 2010 Jul 2;329(5987):72-5
references.pmid: 20466884
references.citation: J Exp Biol. 2010 Aug 1;213(Pt 15):2565-74
references.pmid: 20639417
references.citation: Science. 2013 Jun 14;340(6138):1324-7
references.pmid: 23766324
references.citation: Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15504-9
references.pmid: 14668441
references.citation: Genome Res. 2014 Aug;24(8):1308-15
references.pmid: 24721644
references.citation: Mol Biol Evol. 2009 Dec;26(12):2849-64
references.pmid: 19723671
references.citation: Annu Rev Pathol. 2011;6:165-92
references.pmid: 20939709
references.citation: Mol Biol Evol. 2014 May;31(5):1200-5
references.pmid: 24520091
references.citation: Proc Natl Acad Sci U S A. 2009 Dec 15;106(50):21230-5
references.pmid: 19955425
references.citation: Nat Genet. 2008 Mar;40(3):340-5
references.pmid: 18246066
references.citation: Science. 2002 Nov 22;298(5598):1610-3
references.pmid: 12446907
references.citation: Mol Biol Evol. 2011 Feb;28(2):1075-81
references.pmid: 21030426
references.citation: Mol Biol Evol. 2012 Nov;29(11):3359-70
references.pmid: 22628534
references.citation: Evolution. 1984 Nov;38(6):1358-1370
references.pmid: 28563791