Abstract
Human populations at high altitude exhibit both unique physiological responses and strong genetic signatures of selection thought to compensate for the decreased availability of oxygen in each breath of air. With the increased availability of genomic information from Tibetans, Andeans, and Ethiopians, much progress has been made to elucidate genetic adaptations to chronic hypoxia that have occurred throughout hundreds of generations in these populations. In this perspectives piece, we discuss specific hypoxia-pathway variants that have been identified in high-altitude populations and methods for functional investigation, which may be used to determine the underlying causal factors that afford adaptation to high altitude.
Highlights
Many of humankind’s smallest but greatest secrets are packaged within the human genome
Given that many highland populations have persisted in such environments for hundreds of generations, it was hypothesized that genetic factors provided an adaptive advantage in these groups
While many of the original studies of highland Tibetan, Andean, and Ethiopian populations were based on analysis of “tagging” single nucleotide changes scattered throughout the genome, whole genome sequencing (WGS) tools have afforded an opportunity to cultivate multiple large-scale genome datasets, which provide greater resolution for cross-population comparisons
Summary
Many of humankind’s smallest but greatest secrets are packaged within the human genome. Seq-ing Higher Ground advances have provided additional multi-omics insights (e.g., transcriptomics, epigenomics, proteomics, metabolomics), and gene-editing techniques are available to manipulate and assess the functional consequences of specific genetic variants and their impact on molecular and physiological pathways. This wealth of information regarding genomic, -omics, and functional variation provides an opportunity to more comprehensively examine aspects of evolutionary change in highlanders and place this information into the context of other large-scale, publicly available data sets. While the functional variants have yet to be determined, these studies suggest archaic genetic admixture provided variation that helped Tibetans adapt to the high-altitude environment. This finding highlights the importance of understanding distinct population histories, and unique genetic backgrounds, in studies of genetic adaptation to high altitude
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