Measuring high-altitude adaptation

Abstract

High altitudes (>8,000 ft or 2,500 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, although 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.NEW & NOTEWORTHY Variation in O₂ transport characteristics among Andean, Tibetan, and, when available, Ethiopian high-altitude residents supports the existence of genetic adaptations that improve the distribution of blood flow to vital organs and the efficiency of O₂ utilization. Genome scans and whole genome sequencing studies implicate a broad range of gene regions. Future studies are needed using phenotypes of clear relevance for reproductive success for determining the mechanisms by which naturally selected genes are acting.

Keywords: Andes; Chronic Mountain Sickness; Tibet; hypoxia; pregnancy.

Fig. 1.

The O₂ transport system comprises two pumps, the lungs and the heart, that bring in O₂ from the atmosphere and circulates it via the blood throughout the body, and two diffusion steps. The diffusion steps transfer O₂ across the alveolar membrane and from the blood into tissues where it is consumed in the mitochondria to generate chemical energy in the form of adenosine triphosphate (ATP). Acclimatization involves changes in these components over days and developmental responses take place across lifetimes in chiefly the components affecting arterial O₂ content. Long-term high-altitude populations are distinguished from acclimatized newcomers in terms of their hemoglobin levels, regional blood flow, and O₂ utilization components of the O₂ transport system. [Adapted from Moore (99) with permission from Elsevier. Copyright © 2016 Elsevier.]

Fig. 2.

A: hemoglobin levels in Ethiopians and Tibetans are similar to those of US sea-level residents and below those seen Andean males or females at the altitudes shown[Reproduced from Beall et al. (10) with permission from the National Academy of Sciences. Copyright © 2002 National Academy of Sciences.]. Values among the high-altitude groups are, however, more similar if comparisons are made with acclimatized newcomers (see Table 2). B: Tibetans and Andeans have approximately half the altitude-associated reduction in infant birth weight compared with Europeans or Han Chinese [see text for details and (110) for original references]. C: prevalence of chronic mountain sickness (CMS) is markedly less in Tibetans than similarly aged men from various ancestry groups residing at the altitudes shown. Original references may be found in . [Adapted from Niermeyer et al. (110) with permission from SAGE Publications.]

Fig. 3.

Adaptive challenges or those affecting reproductive success occur at high altitudes at multiple times across the lifespan. About half cluster during the perinatal period or that from gestation through the first week of postnatal life, with the remainder occurring during adolescence or adulthood (see text for references). There is increased mortality from chronic obstructive lung disease (105), but whether mortality from heart disease is affected as well is uncertain (13, 109).