Abstract
Archaeological evidence shows that humans began living in the high altitude Andes approximately 12,000 years ago. Andean highlanders are known to have developed the most complex societies of pre-Columbian South America despite challenges to their health and reproductive success resulting from chronic exposure to hypoxia. While the physiological adaptations to this environmental stressor are well studied in contemporary Andean highlanders, the molecular evolutionary processes associated with such adaptations remain unclear. We aim to better understand how humans managed to demographically establish in this harsh environment by addressing a central question: did exposure to hypoxia drive adaptation via natural selection within Andean populations or did an existing phenotype –characterized by reduced susceptibility to hypoxic stress–enable human settlement of the Andes? We genotyped three variable loci within the NOS3 and EGLN1 genes previously associated with adaptation to high altitude in 150 ancient human DNA samples from Peruvian high altitude and coastal low altitude sites in a time frame between ~8500–560 BP. We compare the data of 109 successful samples to forward simulations of genetic drift with natural selection and find that selection, rather than drift, explains the gradual frequency changes observed in the highland populations for two of the three SNPs.
Highlights
Humans residing in the high altitude Central Andes are directly and indirectly affected by two primary environmental extremes: hypobaric hypoxia and cold
To better understand if and how evolutionary forces might have contributed to the development ofthe genetic diversity of Andean high altitude populations due to the exposure to hypoxia we analyzed three single nucleotide polymorphism (SNP) in two different candidate genes previously associated with response to hypoxic stress (NOS3: rs1799983; EGLN1: rs1769792, rs1769813) in 150 pre-Columbian individuals dating from ~8,500 to 600 BP. 85 samples derive from archaeological sites in the Peruvian highlands; 65 samples from low altitude coastal sites were included for comparative purposes (Fig. 1; Table 1)
Because of the recent advances in genomics, and a growing number of studies identifying candidate genes involved in particular pathways with hypothesized roles in high-altitude adaptation, it is possible to directly test the hypothesis that beneficial traits evolved under selection and contributed to the survivability and success of societies living in the high altitude environments of the Andes
Summary
Humans residing in the high altitude Central Andes (above 2,500 m.a.s.l.) are directly and indirectly affected by two primary environmental extremes: hypobaric hypoxia and cold. While most traits ameliorate negative effects of hypoxia, others could represent maladaptation, e.g. CMS These distinctive phenotypes observed in Andean highlanders and the relatively short time period since the onset of human presence in the high altitude Andes (~480 generations) would suggest strong selective pressures upon putatively beneficial traits[2,9,10]. To better understand if and how evolutionary forces might have contributed to the development ofthe genetic diversity of Andean high altitude populations due to the exposure to hypoxia we analyzed three SNPs in two different candidate genes previously associated with response to hypoxic stress (NOS3: rs1799983; EGLN1: rs1769792, rs1769813) in 150 pre-Columbian individuals dating from ~8,500 to 600 BP. These observations inform our expectation that the G-allele of rs1799983 should increase the fitness of individuals exposed to hypoxic stress
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