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.

Keywords: Andean; Ethiopian; Tibetan; adaptation; altitude; genetics; physiology.

FIG. 1.

Map with three locations where high-altitude adapted populations have lived for hundreds of generations. (Image modified from http://www.nasa.gov/topics/earth/features/20090629.html; low elevations are purple, medium elevations are greens and yellows, and high elevations are orange, red and white.)

FIG. 2.

Selective sweep in human genomes across evolutionary time. Each panel represents a collection of the same chromosomal region sampled at successive generations over time. A beneficial genetic variant will increase in frequency over many generations, leaving a pattern of decreased genetic variation (extended haplotype homozygosity). The first panel represents a neutrally evolving region; the second and third panels represent signals detected from an incomplete and complete selective sweep, respectively, that occurred over many generations of selective pressure. In the latter case, the region harboring the adaptive genetic variant(s) is fixed (or nearly fixed) in the population.