title: Admixture facilitates genetic adaptations to high altitude in Tibet.
abstract: Admixture is recognized as a widespread feature of human populations, renewing interest in the possibility that genetic exchange can facilitate adaptations to new environments. Studies of Tibetans revealed candidates for high-altitude adaptations in the EGLN1 and EPAS1 genes, associated with lower haemoglobin concentration. However, the history of these variants or that of Tibetans remains poorly understood. Here we analyse genotype data for the Nepalese Sherpa, and find that Tibetans are a mixture of ancestral populations related to the Sherpa and Han Chinese. EGLN1 and EPAS1 genes show a striking enrichment of high-altitude ancestry in the Tibetan genome, indicating that migrants from low altitude acquired adaptive alleles from the highlanders. Accordingly, the Sherpa and Tibetans share adaptive haemoglobin traits. This admixture-mediated adaptation shares important features with adaptive introgression. Therefore, we identify a novel mechanism, beyond selection on new mutations or on standing variation, through which populations can adapt to local environments.
authors: Department of Human Genetics, University of Chicago, Chicago, Illinois 60637, USA.
authors: Choongwon
authors: C
authors: Jeong
authors: Department of Human Genetics, University of Chicago, Chicago, Illinois 60637, USA.
authors: Gorka
authors: G
authors: Alkorta-Aranburu
authors: Oxford University Clinical Research Unit, Patan Hospital, Lal Durbar marg, GPO Box 3596, Kathmandu, Nepal.
authors: Buddha
authors: B
authors: Basnyat
authors: Mountain Medicine Society of Nepal, Maharajgunj, Kathmandu, Nepal.
authors: Maniraj
authors: M
authors: Neupane
authors: Department of Human Genetics, University of Chicago, Chicago, Illinois 60637, USA.
authors: David B
authors: DB
authors: Witonsky
authors: 1] Department of Human Genetics, University of Chicago, Chicago, Illinois 60637, USA [2] Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA [3].
authors: Jonathan K
authors: JK
authors: Pritchard
authors: Department of Anthropology, Case Western Reserve University, Cleveland, Ohio 44106-7125, USA.
authors: Cynthia M
authors: CM
authors: Beall
authors: Department of Human Genetics, University of Chicago, Chicago, Illinois 60637, USA.
authors: Anna
authors: A
authors: Di Rienzo
mesh_terms: D000220:Adaptation, Biological; D000328:Adult; D000531:Altitude; D044466:Asian People / Q000235:genetics*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D005260:Female; D051456:Gene Flow; D006801:Humans; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018609:Tibet; D055815:Young Adult; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D000099162:Endothelial PAS Domain-Containing Protein 1; C490190:EGLN1 protein, human