Phenotypic plasticity, genetic assimilation, and genetic compensation in hypoxia adaptation of high-altitude vertebrates

Abstract

Important questions about mechanisms of physiological adaptation concern the role of phenotypic plasticity and the extent to which acclimatization responses align with genetic responses to selection. Such questions can be addressed in experimental studies of high-altitude vertebrates by investigating how mechanisms of acclimatization to hypoxia in lowland natives may influence genetic adaptation to hypoxia in highland natives. Evidence from high-altitude mammals suggest that evolved changes in some physiological traits involved canalization of the ancestral acclimatization response to hypoxia (genetic assimilation), a mechanism that results in an evolved reduction in plasticity. In addition to cases where adaptive plasticity may have facilitated genetic adaptation, evidence also suggests that some physiological changes in high-altitude natives are the result of selection to mitigate maladaptive plastic responses to hypoxia (genetic compensation). Examples of genetic compensation involve the attenuation of hypoxic pulmonary hypertension in Tibetan humans and other mammals native to high altitude. Here we discuss examples of adaptive physiological phenotypes in high-altitude natives that may have evolved by means of genetic assimilation or genetic compensation.

Figure 1.

Role of phenotypic plasticity in adaptation to a newly colonized environment. (A) Hypothetical scenario in which fitness varies as a function of phenotypic trait values in an ancestral, lowland environment. The trait value that confers the highest fitness is denoted by a vertical dashed line. (B) In the high-altitude environment, the fitness function of the phenotype is shifted relative to that in the lowland environment. The high-altitude phenotypic optimum is denoted by the solid vertical line. Upon colonization of the high-altitude environment, a plastic response (black arrow) moves the population mean phenotype to the new optimum. In this scenario, adaptive plasticity in the fitness-related phenotype eliminates the opportunity for selection on genetically based trait variation. (C) A plastic response (black arrow) moves the population mean phenotype part way to the new optimum, and selection on genetically based variation (orange arrow) then shifts it the rest of the way. (D) A maladaptive plastic response (black arrow) moves the population mean further from the new optimum, and selection on genetically based variation (orange arrow) then compensates the environmentally induced change in phenotype.

Figure 2.

Evolutionary changes in phenotypic plasticity and consequences for observed patterns of trait variation. (A) Genetic assimilation. The fitness function for the trait in question is different in the ancestral lowland environment and the newly colonized highland environment. The hypoxia-induced plastic response is adaptive (reaction norm illustrated with solid line) and becomes canalized by selection, resulting in the loss of plasticity. Far right panel: Hypothetical outcome of reciprocal-transplant experiment showing expression of the phenotype when highlanders and lowlanders are reared in native and nonnative environments. Arrow heads denote outcomes of reciprocal transplants (phenotypes expressed in the non-native environment). Highlanders and lowlanders exhibit a pronounced difference in phenotype (ΔP) when observed in their native habitats, and the reciprocal transplant reveals the loss of plasticity in highlanders. (B) Genetic compensation with canalization. Fitness function for the trait is the same in the lowland and highland environments. The hypoxia-induced plastic response shifts the mean trait value away from the global optimum. In highland natives, selection on genetically based trait variation counteracts the plastic change, thereby restoring the ancestral phenotype (i.e., the same phenotype expressed by lowland natives in the ancestral environment). Far right panel: Highlanders and lowlanders exhibit no difference in phenotype when observed in their native habitats (ΔP=0), and the reciprocal transplant reveals the loss of plasticity in highlanders. (C) Genetic compensation without canalization. Same scenario as in B, but the highland population evolves a new reaction norm without a concomitant loss of plasticity (change in Y-intercept, but no change in slope). Far right panel: Highlanders and lowlanders exhibit no difference in phenotype when observed in their native habitats (ΔP=0), and the reciprocal transplant reveals that they exhibit plastic responses in opposite directions when reared in nonnative environments.

Figure 3.

Large-scale deletion in the β-globin gene cluster of Tibetan antelope is revealed by analysis of pairwise sequence matches with homologous chromosomal regions in other bovids. Cyan, green, and dark blue boxes represent members of triplicated gene blocks containing the genes that encode the β-type subunits of juvenile (β^C), adult (β^A), and fetal (β^F) Hb isoforms, respectively. (a) Gray shading denotes percent sequence identity between homologous β-globin gene clusters. (b) A ~45 kb chromosomal deletion in the β-globin gene cluster of Tibetan antelope resulted in secondary loss of the β^A-containing gene block. Modified with permission from Signore and Storz (2020).

Figure 4.

Exposure to chronic hypoxia led to (A) pulmonary hypertension (increased right-ventricle systolic pressure) and (B) right-ventricle hypertrophy (increased right ventricle mass relative to the combined mass of the left ventricle and septum) in deer mouse populations from low altitude, but these effects were attenuated in populations from high altitude. Data are means ± SE. * Significant differences between populations within an environment (P<0.05). Modified with permission from West et al. (2021).