title: The Andean adaptive toolkit to counteract high altitude maladaptation: genome-wide and phenotypic analysis of the Collas.
abstract: During their migrations out of Africa, humans successfully colonised and adapted to a wide range of habitats, including extreme high altitude environments, where reduced atmospheric oxygen (hypoxia) imposes a number of physiological challenges. This study evaluates genetic and phenotypic variation in the Colla population living in the Argentinean Andes above 3500 m and compares it to the nearby lowland Wichí group in an attempt to pinpoint evolutionary mechanisms underlying adaptation to high altitude hypoxia. We genotyped 730,525 SNPs in 25 individuals from each population. In genome-wide scans of extended haplotype homozygosity Collas showed the strongest signal around VEGFB, which plays an essential role in the ischemic heart, and ELTD1, another gene crucial for heart development and prevention of cardiac hypertrophy. Moreover, pathway enrichment analysis showed an overrepresentation of pathways associated with cardiac morphology. Taken together, these findings suggest that Colla highlanders may have evolved a toolkit of adaptative mechanisms resulting in cardiac reinforcement, most likely to counteract the adverse effects of the permanently increased haematocrit and associated shear forces that characterise the Andean response to hypoxia. Regulation of cerebral vascular flow also appears to be part of the adaptive response in Collas. These findings are not only relevant to understand the evolution of hypoxia protection in high altitude populations but may also suggest new avenues for medical research into conditions where hypoxia constitutes a detrimental factor.
authors.affiliation: Division of Biological Anthropology, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Eichstaedt
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, Oxfordshire, United Kingdom.
authors.forename: Tiago
authors.initials: T
authors.lastname: Antão
authors.affiliation: Division of Biological Anthropology, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom; Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, United Kingdom.
authors.forename: Luca
authors.initials: L
authors.lastname: Pagani
authors.affiliation: Division of Biological Anthropology, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom.
authors.forename: Alexia
authors.initials: A
authors.lastname: Cardona
authors.affiliation: Division of Biological Anthropology, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom.
authors.forename: Toomas
authors.initials: T
authors.lastname: Kivisild
authors.affiliation: Division of Biological Anthropology, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom; School of Chemistry, University of East Anglia, Norwich, Norfolk, United Kingdom.
authors.forename: Maru
authors.initials: M
authors.lastname: Mormina
mesh_terms: D000064:Acclimatization / Q000235:genetics*; D000222:Adaptation, Physiological / Q000235:genetics*; D000531:Altitude; D005075:Biological Evolution; D017753:Ecosystem; D005828:Genetics, Population / Q000379:methods; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D000860:Hypoxia / Q000235:genetics; D010100:Oxygen / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013020:South America
chemical_list: D010100:Oxygen