The Andean Adaptive Toolkit to Counteract High Altitude Maladaptation: Genome-Wide and Phenotypic Analysis of the Collas.

Mormina, Maru and Eichstaedt, Christina and Antao, Tiago and Pagani, Luca and Cardona, Alexia and Kivisild, Toomas (2014) The Andean Adaptive Toolkit to Counteract High Altitude Maladaptation: Genome-Wide and Phenotypic Analysis of the Collas. PLOS One, 9 (3). pp. 1-2. ISSN 1932-6203

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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 Wichı´ 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.

Item Type: Article
Additional Information: This work was supported by European Research Council Starting Investigator grant (FP7-261213, TK), a starting investigator grant from the University of East Anglia (RC-158, MM) and the Young Explorers Grant from the National Geographic Society http://www. (8900-11, CE). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Uncontrolled Keywords: adult; altitude acclimatization; altitude disease; Argentina; article; body mass; body weight; brain blood flow; breathing pattern; ELTD1 gene; gene; gene flow; gene frequency; genetic variability; heart output; heart rate; hematocrit; homozygosity; human; human experiment; normal human; oxygen saturation; single nucleotide polymorphism; systolic blood pressure; VEGFB gene; acclimatization; adaptation; altitude; anoxia; ecosystem; evolution; genetic association; genetics; genotype; metabolism; population genetics; procedures; South America
Subjects: C Biological sciences > C170 Population biology
C Biological sciences > C182 Evolution
C Biological sciences > C420 Human genetics
C Biological sciences > C450 Genomics
Depositing User: Maru Mormina
Date Deposited: 18 Apr 2016 12:49
Last Modified: 18 Apr 2016 12:49

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