Exploring the genetic footprints of high altitude adapted humans and livestock

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Abstract
High-altitude environments such as the Himalayas, Andes, and Ethiopian regions pose extreme environmental challenges like hypobaric hypoxia, cold stress, and extreme UV radiation. This prompts both short-term physiological and long-term genetic adaptations in resident human and livestock populations. Various genetic studies suggest that candidate genes, such as HIF1A, EPAS1, EGLN1, MITF, ITPR2, VEGFA etc. are involved in hypoxia response, erythropoiesis, angiogenesis and metabolic regulation that results in high altitude adaptation. Phylogenetic comparisons of HIF family genes, suggest evolutionary divergence between humans and livestock, however, closer relationships exist among the ruminants suggesting shared adaptive pressures. The present study revealed that despite of the different evolutionary history, both humans and livestock across the different geographical regions show similar type of traits, driven by certain genes (either the same genes or different genes working in similar ways). These genes have been naturally selected over the time and helped the humans and livestock to survive at extreme environments. Furthermore, enrichment analysis suggests convergent evolution at the gene and pathway levels, supporting the genetic adaption in humans and livestock across the different geographical regions. This review will serve as a valuable information source for researchers working in the fields of high-altitude environments, evolutionary biology and environmental genomics.

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