Genomic insights into adaptation to high-altitude environments

Abstract

Elucidating the molecular genetic basis of adaptive traits is a central goal of evolutionary genetics. The cold, hypoxic conditions of high-altitude habitats impose severe metabolic demands on endothermic vertebrates, and understanding how high-altitude endotherms cope with the combined effects of hypoxia and cold can provide important insights into the process of adaptive evolution. The physiological responses to high-altitude stress have been the subject of over a century of research, and recent advances in genomic technologies have opened up exciting opportunities to explore the molecular genetic basis of adaptive physiological traits. Here, we review recent literature on the use of genomic approaches to study adaptation to high-altitude hypoxia in terrestrial vertebrates, and explore opportunities provided by newly developed technologies to address unanswered questions in high-altitude adaptation at a genomic scale.

Figure 1

Schematic representation of HIF regulation of erythropoiesis. Gray boxes represent genome scan-nominated candidate genes that have been hypothesized to contribute to the blunted erythropoietic response in Tibetans. The genes in the white boxes are provided for reference. Note that for simplicity, many other genes that participate in erythropoiesis (for example, hepcidin, ferroportin, transferrin and Janus kinase) have been omitted. Figure modified from those in Semenza (2009) and Simonson et al. (2010).

Figure 2

Functional differences between high- and low-altitude deer mouse hemoglobin isoforms. P₅₀ represents the pO₂ at which hemoglobin is 50% saturated, and lower P₅₀ values indicate higher oxygen affinity. High-altitude isoforms exhibit higher oxygen affinity than low-altitude isoforms (lower P₅₀ values) in the presence of allosteric cofactors (2,3 DPG and Cl⁻ ions), but oxygen affinities are similar in their absence. These results demonstrate that differences in oxygen affinity are because of differences in their sensitivity to these erythrocytic allosteric cofactors. Figure modified from data presented in Storz et al. (2009, 2010a).

Figure 3

Cytochrome oxidase kinetics in bar-headed geese. Bar-headed geese differ from lowland congeners in (a) Michaelis–Menton enzyme kinetics, (b) substrate affinity (K_m) and (c) maximal cytochrome oxidase activity (V_max). ^*Significant differences (P<0.05) from both species of lowland geese. Figure modified from Scott et al. (2011).