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.
Highlights
In the last 40,000 years modern humans have undergone a series of rapid adaptive changes in response to new environmental pressures as they spread from Africa into new habitats [1]
It is only very recently that Ethiopians highlanders were included in genomic High altitude (HA) studies [92,93,94] and only three published genome-wide studies in Andeans are currently available [15,16,17], all including Quechua or Aymara populations
The Colla group chosen for this study is a HA population with recent shared ancestry to Aymara and Quechua, yet with sufficient degree of geographic isolation to provide an independent study group
Summary
In the last 40,000 years modern humans have undergone a series of rapid adaptive changes in response to new environmental pressures as they spread from Africa into new habitats [1]. Effective adaptive mechanisms are known to be in place to contend with the effects of chronic hypoxia. These are known to differ and be convergent among the main HA populations: Tibetans, Andeans and Ethiopians [4]. Given the relatively recent time scale of peopling of the Himalayas and the Andes [5] these convergent patterns suggest strong selective pressures upon putative beneficial traits. As hypoxia is a major factor in a number of pathologies [2,6], HA populations represent an ideal natural experiment to understand the biology of the hypoxic response
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