Genetic Convergence in the Adaptation of Dogs and Humans to the High-Altitude Environment of the Tibetan Plateau

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.

• Publication year

  2014

• Venue

  Genome Biology and Evolution

• Publication date

  2014-08-01

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.1093/gbe/evu162PMID 25091388PMCID 4231634
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Population variation revealed high-altitude adaptation of Tibetan mastiffs.

  2014cited by this paper
• Whole-genome sequencing of six dog breeds from continuous altitudes reveals adaptation to high-altitude hypoxia

  2014cited by this paper
• Repeated elevational transitions in hemoglobin function during the evolution of Andean hummingbirds

  2013cited by this paper
• Epistasis Among Adaptive Mutations in Deer Mouse Hemoglobin

  2013cited by this paper
• The genomics of selection in dogs and the parallel evolution between dogs and humans

  2013cited by this paper
• The Genetic Architecture of Adaptations to High Altitude in Ethiopia

  2012cited by this paper
• Oxygen transport by hemoglobin.

  2012cited by this paper
• High genetic diversity of Tibetan Mastiffs revealed by mtDNA sequences

  2012cited by this paper
• Genetic adaptation to high altitude in the Ethiopian highlands

  2012cited by this paper
• Genetic adaptation of the hypoxia-inducible factor pathway to oxygen pressure among eurasian human populations.

  2012cited by this paper
• Genetic variations in Tibetan populations and high-altitude adaptation at the Himalayas.

  2011cited by this paper
• The HIF pathway and erythrocytosis.

  2011cited by this paper
• A genome-wide search for signals of high-altitude adaptation in Tibetans.

  2011cited by this paper
• Genetic differences in hemoglobin function between highland and lowland deer mice

  2010cited by this paper
• A method and server for predicting damaging missense mutations

  2010cited by this paper
• Natural selection on EPAS1 (HIF2α) associated with low hemoglobin concentration in Tibetan highlanders

  2010cited by this paper
• Identifying Signatures of Natural Selection in Tibetan and Andean Populations Using Dense Genome Scan Data

  2010cited by this paper
• Genetic Evidence for High-Altitude Adaptation in Tibet

  2010cited by this paper
• Sequencing of 50 Human Exomes Reveals Adaptation to High Altitude

  2010cited by this paper
• mtDNA Data Indicate a Single Origin for Dogs South of Yangtze River, Less Than 16,300 Years Ago, from Numerous Wolves

  2009cited by this paper
• The Sequence Alignment/Map format and SAMtools

  2009cited by this paper
• Artificial ligand binding within the HIF2α PAS-B domain of the HIF2 transcription factor

  2009cited by this paper
• Principles of ligand binding within a completely buried cavity in HIF2alpha PAS-B.

  2009influential reference
• Mitochondrial genome evidence reveals successful Late Paleolithic settlement on the Tibetan Plateau

  2009cited by this paper
• Evolutionary and functional insights into the mechanism underlying high-altitude adaptation of deer mouse hemoglobin

  2009cited by this paper
• Natural selection has driven population differentiation in modern humans

  2008cited by this paper
• Mechanisms of Hemoglobin Adaptation to High Altitude Hypoxia

  2008cited by this paper
• Colloquium Papers: Two routes to functional adaptation: Tibetan and Andean high-altitude natives

  2007cited by this paper
• Efficient mapping of mendelian traits in dogs through genome-wide association

  2007cited by this paper
• Genome sequence, comparative analysis and haplotype structure of the domestic dog

  2005influential reference
• Theoretical and practical advances in genome halving

  2004cited by this paper
• Canine and feline hematology reference values for the ADVIA 120 hematology system.

  2004influential reference
• Structural basis for PAS domain heterodimerization in the basic helix–loop–helix-PAS transcription factor hypoxia-inducible factor

  2003cited by this paper
• Interrogating a high-density SNP map for signatures of natural selection.

  2002influential reference
• Genetic Evidence for an East Asian Origin of Domestic Dogs

  2002cited by this paper
• Linkage disequilibrium in the human genome

  2001cited by this paper
• Cn3D: sequence and structure views for Entrez.

  2000cited by this paper
• Origins of the dog: domestication and early history

  1995cited by this paper
• ESTIMATING F‐STATISTICS FOR THE ANALYSIS OF POPULATION STRUCTURE

  1984influential reference
• Transport of Oxygen through Hemoglobin Solutions

  1961cited by this paper

• Review: Genomic insights into the adaptive traits and stress resistance in modern horses

  2026cites this paper
• Phylogenomics provides comprehensive insights into the evolutionary relationships among cultivated buckwheat species

  2025cites this paper
• Exploring the genetic footprints of high altitude adapted humans and livestock

  2025cites this paper
• Genomics provides insights into high‐altitude adaptation in plateau brown frog

  2025cites this paper
• The Vulpes vulpes montana genome provides insights into high-altitude adaptation mechanisms of the Vulpes species

  2025cites this paper
• Integrative Genomic, Transcriptomic and Epigenomic Analysis Reveals cis-regulatory Contributions to High-altitude Adaptation in Tibetan Pigs

  2025cites this paper
• Structural Variations Associated with Adaptation and Coat Color in Qinghai‐Tibetan Plateau Cattle

  2025cites this paper
• Shennong 1 Chicken 40K Liquid Chip: Advancing Genetic Research in Chinese Indigenous Chickens

  2025cites this paper
• Earliest sustained settlement by farmers and symbiotic relationship with foragers at high altitude on the Tibetan Plateau

  2025cites this paper
• Knockout of the fih gene by CRISPR/Cas9 enhances the hypoxia tolerance in grass carp(Ctenopharyngodon idella)

  2025cites this paper
• Early findings from the Dog Aging Project

  2024cites this paper
• A missing paradigm: deciphering endocrine innovations among diverging regulations of alleles, paralogous and orthologous genes.

  2024cites this paper
• Genomic insights into the genetic diversity, lateral gaits and high-altitude adaptation of Chakouyi (CKY) horses.

  2024cites this paper
• Human-directed sociability in the domestic dog: a Tinbergian approach.

  2024cites this paper
• Whole-genome resequencing of Chinese indigenous sheep provides insight into the genetic basis underlying climate adaptation

  2024cites this paper
• North African fox genomes show signatures of repeated introgression and adaptation to life in deserts

  2023cites this paper
• Hypoxia Inducible Factor pathway proteins in high-altitude mammals.

  2023cites this paper
• Convergent evolution of the environmental adaptability of high‐elevation populations of waist‐shaped bugs

  2023cites this paper
• Deletion of prolyl hydroxylase domain-containing enzyme 3 (phd3) in zebrafish facilitates hypoxia tolerance

  2023cites this paper
• Genetic and cultural adaptations underlie the establishment of dairy pastoralism in the Tibetan Plateau

  2023cites this paper
• Quelle relation existe-t-il entre l’importance fonctionnelle d’un gène et son degré de polymorphisme? Un point de vue intra- et interespèces

  2023cites this paper
• Being a Dog: A Review of the Domestication Process

  2023cites this paper
• A highland-adaptation mutation of the Epas1 protein increases its stability and disrupts the circadian clock in the plateau pika.

  2022cites this paper
• Convergent Genomic Signatures of High-Altitude Adaptation among Six Independently Evolved Mammals

  2022cites this paper
• Genomic differentiation with isolation by distance along a latitudinal gradient in the spotted-leg treefrog Polypedates megacephalus.

  2022cites this paper
• Gene essentiality and variability: What is the link? A within‐ and between‐species perspective

  2022cites this paper
• Chromosome-level Genome Assembly of the High-altitude Leopard (Panthera pardus) Sheds Light on Its Environmental Adaptation

  2022cites this paper
• Time Domains of Hypoxia Responses and -Omics Insights

  2022cites this paper
• Whole-Genome Analysis Deciphers Population Structure and Genetic Introgression Among Bovine Species

  2022cites this paper
• Evolutionary Conservation Genomics Reveals Recent Speciation and Local Adaptation in Threatened Takins

  2022cites this paper
• Comparative genomic analysis of high-altitude adaptation for Mongolia Mastiff, Tibetan Mastiff, and Canis Lupus.

  2022cites this paper
• Comparing wolves and dogs: current status and implications for human 'self-domestication'.

  2022cites this paper
• Pervasive genomic signatures of local adaptation to altitude across highland specialist Andean hummingbird populations.

  2021cites this paper
• Long distance migration is a major factor driving local adaptation at continental scale in Coho Salmon

  2021cites this paper
• Efecto de marcadores genéticos moleculares en genes inducibles por hipoxia de bovinos criollos y Brown Swiss criados en los Andes de Perú

  2021cites this paper
• FGF5 and EPAS1 gene polymorphisms are associated with high-altitude adaptation in Nepalese goat breeds.

  2021cites this paper
• Recent progress in research on the gut microbiota and highland adaptation on the Qinghai‐Tibet Plateau

  2021cites this paper
• Population Genomics of High-Altitude Adaptation

  2021cites this paper
• Application of a novel haplotype‐based scan for local adaptation to study high‐altitude adaptation in rhesus macaques

  2021cites this paper
• Genomic analysis of field pennycress (Thlaspi arvense) provides insights into mechanisms of adaptation to high elevation

  2021cites this paper
• Whole-Genome Sequencing Reveals Lactase Persistence Adaptation in European Dogs

  2021cites this paper
• Genome and population evolution and environmental adaptation of Glyptosternon maculatum on the Qinghai-Tibet Plateau

  2021cites this paper
• Hb adaptation to hypoxia in high-altitude fishes: Fresh evidence from schizothoracinae fishes in the Qinghai-Tibetan Plateau.

  2021cites this paper
• Genomes reveal selective sweeps in kiang and donkey for high-altitude adaptation

  2021cites this paper
• Introgressive Hybridization and Hypoxia Adaptation in High-Altitude Vertebrates

  2021cites this paper
• Adaptive introgression of the beta-globin cluster in two Andean waterfowl

  2021cites this paper
• Aconiti lateralis Radix Praeparata inhibits Alzheimer’s disease by regulating the complex regulation network with the core of GRIN1 and MAPK1

  2021influential citation
• Genome-wide comparative analyses reveal selection signatures underlying adaptation and production in Tibetan and Poll Dorset sheep

  2021cites this paper
• Using seasonal genomic changes to understand historical adaptation to new environments: Parallel selection on stickleback in highly‐variable estuaries

  2021cites this paper
• High-altitude adaptation in rhesus macaques

  2020cites this paper
• Selection signatures for high-altitude adaptation in ruminants.

  2020cites this paper
• Deciphering the puzzles of dog domestication

  2020cites this paper
• Genetic Adaptation in New York City Rats

  2020cites this paper
• The Genomics and Genetics of Oxygen Homeostasis.

  2020cites this paper
• Evidence of Echolocation in the Common Shrew from Molecular Convergence with Other Echolocating Mammals.

  2020cites this paper
• The Domestication Makeup: Evolution, Survival, and Challenges

  2020cites this paper
• Cross-Species Insights Into Genomic Adaptations to Hypoxia

  2020cites this paper
• Comparative microRNA Transcriptomes in Domestic Goats Reveal Acclimatization to High Altitude

  2020cites this paper
• Goat Genomic Resources: The Search for Genes Associated with Its Economic Traits

  2020cites this paper
• Parámetros ecocardiográficos y electrocardiográficos en caninos atletas de la raza Border Collie en gran altitud

  2020cites this paper
• Accelerated evolution and positive selection of rhodopsin in Tibetan loaches living in high altitude.

  2020cites this paper
• Using seasonal genomic changes to understand historical adaptation: parallel selection on stickleback in highly-variable estuaries

  2020cites this paper
• Comparative genome analyses reveal the unique genetic composition and selection signals underlying the phenotypic characteristics of three Chinese domestic goat breeds

  2019cites this paper
• Convergent genomic signatures of high-altitude adaptation among domestic mammals

  2019cites this paper
• EPAS1 Gain-of-Function Mutation Contributes to High-Altitude Adaptation in Tibetan Horses

  2019influential citation
• Comparative analysis of peripheral blood reveals transcriptomic adaptations to extreme environments on the Qinghai-Tibetan Plateau in the gray wolf (Canis lupus chanco)

  2019cites this paper
• Dog10K: an international sequencing effort to advance studies of canine domestication, phenotypes and health

  2019cites this paper
• Divergent Fine-Scale Recombination Landscapes between a Freshwater and Marine Population of Threespine Stickleback Fish

  2019cites this paper
• Chromosome‐level genome assembly of Triplophysa tibetana, a fish adapted to the harsh high‐altitude environment of the Tibetan Plateau

  2019cites this paper
• Identification of Candidate Genes for the Plateau Adaptation of a Tibetan Amphipod, Gammarus lacustris, Through Integration of Genome and Transcriptome Sequencing

  2019cites this paper
• Convergent evolution on the hypoxia-inducible factor (HIF) pathway genes EGLN1 and EPAS1 in high-altitude ducks

  2019cites this paper
• Genetic Diversity and Signatures of Selection in 15 Chinese Indigenous Dog Breeds Revealed by Genome-Wide SNPs

  2019cites this paper
• Whole-genome sequencing reveals selection signatures associated with important traits in six goat breeds

  2018cites this paper
• Fine-grained genetic-environmenthabitat- associated genetic connectivity ion in an admixed population of mussels in the small isolated Kerguelen island connectivity of marine populations in the genomic era.

  2018cites this paper
• Whole-Genome Sequencing of Three Native Cattle Breeds Originating From the Northernmost Cattle Farming Regions

  2018influential citation
• A Key For Hypoxia Genetic Adaptation In Alpaca Could Be A HIF1A Truncated bHLH Protein Domain

  2018cites this paper
• Structural variation during dog domestication: insights from gray wolf and dhole genomes

  2018cites this paper
• Whole‐Genome Sequencing of African Dogs Provides Insights into Adaptations against Tropical Parasites

  2018cites this paper
• Sequence Characterization of DSG3 Gene to Know Its Role in High-Altitude Hypoxia Adaptation in the Chinese Cashmere Goat

  2018cites this paper
• The Genome Landscape of Tibetan Sheep Reveals Adaptive Introgression from Argali and the History of Early Human Settlements on the Qinghai–Tibetan Plateau

  2018cites this paper
• Transcriptome analysis of the hypothalamic-pituitary-adrenal axis in the experimentally domesticated fox

  2017cites this paper
• Dissecting evolution and disease using comparative vertebrate genomics

  2017cites this paper
• Fine-grained habitat-associated genetic connectivity in an admixed population of mussels in the small isolated Kerguelen Islands

  2017cites this paper
• The companion dog as a unique translational model for aging.

  2017cites this paper
• Genome methylation and regulatory functions for hypoxic adaptation in Tibetan chicken embryos

  2017cites this paper
• Hypoxia Inducible Factor (HIF) transcription factor family expansion, diversification, divergence and selection in eukaryotes

  2017cites this paper
• High-altitude adaptation in humans: from genomics to integrative physiology

  2017cites this paper
• Migration-Selection Balance Drives Genetic Differentiation in Genes Associated with High-Altitude Function in the Speckled Teal (Anas flavirostris) in the Andes

  2017cites this paper
• Comprehensive transcriptomic analysis of Tibetan Schizothoracinae fish Gymnocypris przewalskii reveals how it adapts to a high altitude aquatic life

  2017cites this paper
• Population transcriptomes reveal synergistic responses of DNA polymorphism and RNA expression to extreme environments on the Qinghai–Tibetan Plateau in a predatory bird

  2017cites this paper
• A non-synonymous SNP with the allele frequency correlated with the altitude may contribute to the hypoxia adaptation of Tibetan chicken

  2017cites this paper
• Genomic signature of highland adaptation in fish: a case study in Tibetan Schizothoracinae species

  2017cites this paper
• Genetic signatures of high-altitude adaptation in Tibetans

  2017cites this paper
• Demographic history, selection and functional diversity of the canine genome

  2017cites this paper
• Evidence of high-altitude adaptation in the glyptosternoid fish, Creteuchiloglanis macropterus from the Nujiang River obtained through transcriptome analysis

  2017cites this paper
• Time Domains of the Hypoxic Ventilatory Response and Their Molecular Basis.

  2016cites this paper
• Genomic analysis identified a potential novel molecular mechanism for high-altitude adaptation in sheep at the Himalayas

  2016cites this paper
• Genomewide scan for adaptive differentiation along altitudinal gradient in the Andrew's toad Bufo andrewsi

  2016cites this paper
• Identifying molecular signatures of hypoxia adaptation from sex chromosomes: A case for Tibetan Mastiff based on analyses of X chromosome

  2016cites this paper
• Whole-genome resequencing of Xishuangbanna fighting chicken to identify signatures of selection

  2016cites this paper