Abstract
Humans living at high altitude (≥2,500 meters above sea level) have acquired unique abilities to survive the associated extreme environmental conditions, including hypoxia, cold temperature, limited food availability and high levels of free radicals and oxidants. Long-term inhabitants of the most elevated regions of the world have undergone extensive physiological and/or genetic changes, particularly in the regulation of respiration and circulation, when compared to lowland populations. Genome scans have identified candidate genes involved in altitude adaption in the Tibetan Plateau and the Ethiopian highlands, in contrast to populations from the Andes, which have not been as intensively investigated. In the present study, we focused on three indigenous populations from Bolivia: two groups of Andean natives, Aymara and Quechua, and the low-altitude control group of Guarani from the Gran Chaco lowlands. Using pooled samples, we identified a number of SNPs exhibiting large allele frequency differences over 900,000 genotyped SNPs. A region in chromosome 10 (within the cytogenetic bands q22.3 and q23.1) was significantly differentiated between highland and lowland groups. We resequenced ~1.5 Mb surrounding the candidate region and identified strong signals of positive selection in the highland populations. A composite of multiple signals like test localized the signal to FAM213A and a related enhancer; the product of this gene acts as an antioxidant to lower oxidative stress and may help to maintain bone mass. The results suggest that positive selection on the enhancer might increase the expression of this antioxidant, and thereby prevent oxidative damage. In addition, the most significant signal in a relative extended haplotype homozygosity analysis was localized to the SFTPD gene, which encodes a surfactant pulmonary-associated protein involved in normal respiration and innate host defense. Our study thus identifies two novel candidate genes and associated pathways that may be involved in high-altitude adaptation in Andean populations.
Highlights
It is generally accepted that anatomically modern humans emerged in Africa and radiated from there to colonize most of the world's land masses [1]
We focused on three indigenous populations from Bolivia, namely two groups of native inhabitants living at high altitude (!3600 meters above sea level) in the Andes, Aymara and Quechua, and as a control group the Guarani from the Gran Chaco lowlands
The most common haplogroup found in our collection of Bolivian males was Q, at frequencies of roughly 80% in all three groups (S1 Fig)
Summary
It is generally accepted that anatomically modern humans emerged in Africa and radiated from there to colonize most of the world's land masses [1]. During this “out of Africa” diaspora, modern humans encountered new habitats with a very diverse set of ecological conditions in contrast to the African homeland, e.g., in the form of new geographic environments, climates, diets and/or pathogens. One of the extreme habitats successfully colonized by humans is high altitude. Some populations of humans have developed a physique that enables permanent habitation of high-altitude regions despite the severe conditions of hypoxia and other environmental stressors
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