Altitude Adaptation: A Glimpse Through Various Lenses

Abstract

Simonson, Tatum S. Altitude adaptation: A glimpse through various lenses. High Alt Med Biol 16:125-137, 2015.-Recent availability of genome-wide data from highland populations has enabled the identification of adaptive genomic signals. Some of the genomic signals reported thus far among Tibetan, Andean, and Ethiopian are the same, while others appear unique to each population. These genomic findings parallel observations conveyed by decades of physiological research: different continental populations, resident at high altitude for hundreds of generations, exhibit a distinct composite of traits at altitude. The most commonly reported signatures of selection emanate from genomic segments containing hypoxia-inducible factor (HIF) pathway genes. Corroborative evidence for adaptive significance stems from associations between putatively adaptive gene copies and sea-level ranges of hemoglobin concentration in Tibetan and Amhara Ethiopians, birth weights and metabolic factors in Andeans and Tibetans, maternal uterine artery diameter in Andeans, and protection from chronic mountain sickness in Andean males at altitude. While limited reports provide mechanistic insights thus far, efforts to identify and link precise genetic variants to molecular, physiological, and developmental functions are underway, and progress on the genomics front continues to provide unprecedented movement towards these goals. This combination of multiple perspectives is necessary to maximize our understanding of orchestrated biological and evolutionary processes in native highland populations, which will advance our understanding of both adaptive and non-adaptive responses to hypoxia.

Sea‐level haemoglobin concentration is associated with greater exercise capacity in Tibetan males at 4200 m

“…At the genetic and genomic levels, it will be important to determine the primary targets of adaptation in high-altitude Tibetans (Simonson, 2015). For instance, it will be important to determine whether [Hb] was the direct target of adaptive change, e.g.…”

Human genetic adaptation to high altitudes: Current status and future prospects

“…Unknown is whether the Tibetans’ improved tissue O 2 diffusion and utilization (Holden et al, 1995; Simonson et al, 2015) also occur with lifelong residence. With respect to comparisons among native high-altitude populations, the relatively small number of studies in Ethiopian highlanders makes three-way comparisons difficult but several comprehensive reviews of Andeans and Tibetans have been published (Beall et al, 1990; Bigham and Lee, 2014; Gilbert-Kawai et al, 2014; Holden et al, 1995; Moore, 2001; Moore et al, 1998b; Simonson, 2015; Simonson et al, 2015; Winslow et al, 1989). To summarize, Tibetans compared to Andeans have higher V E at rest and during exercise, marginally lower lung volumes and diffusing capacities, similar levels of SaO 2 , lower Hb concentrations, less hypoxic pulmonary vasoconstriction and hence lower Ppa pressures (Figure 4B), and perhaps better preservation of cardiac function, exercise performance, O 2 diffusion to the muscle and tissue O 2 utilization.…”

The human physiological impact of global deoxygenation

“…Current best estimates place Tibetan plateau settlement first (25,000 years ago) followed by that of the Andean Altiplano (12,000 years ago) with a range of values given for colonization of the Ethiopian plateau (between 5000 and 70,000 years ago), although we cannot prove genetic continuity between original colonizers and modern-day populations [29]. Specific physiological traits, related to the oxygen transport pathway or oxygen utilization, have been identified in these populations, but the composite of traits is different in each.…”