Measuring high-altitude adaptation

High altitudes (>8000 ft or 2500 m) provide an experiment of nature for measuring adaptation and the physiological processes involved. Studies conducted over the past ~25 years in Andeans, Tibetans, and less often Ethiopians show varied but distinct O₂ transport traits from those of acclimatized newcomers, providing indirect evidence for genetic adaptation to high altitude. Short-term (acclimatization, developmental) and long-term (genetic) responses to high altitude exhibit a temporal gradient such that, while all influence O₂ content, the latter also improve O₂ delivery and metabolism. Much has been learned concerning the underlying physiological processes but additional studies are needed on the regulation of blood flow and O₂ utilization. Direct evidence of genetic adaptation comes from single nucleotide polymorphism (SNP)-based genome scans and whole-genome sequencing studies that have identified gene regions acted upon by natural selection. Efforts have begun to understand the connections between the two with Andean studies on the genetic factors raising uterine blood flow, fetal growth, and susceptibility to Chronic Mountain Sickness and Tibetan studies on genes serving to lower hemoglobin and pulmonary arterial pressure. Critical for future studies will be the selection of phenotypes with demonstrable effects on reproductive success, the calculation of actual fitness costs, and greater inclusion of women among the subjects being studied. The well-characterized nature of the O₂ transport system, the presence of multiple long-resident populations, and relevance for understanding hypoxic disorders in all persons underscore the importance of understanding how evolutionary adaptation to high altitude has occurred.

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