Phenotypic plasticity and genetic adaptation to high-altitude hypoxia in vertebrates

Abstract

High-altitude environments provide ideal testing grounds for investigations of mechanism and process in physiological adaptation. In vertebrates, much of our understanding of the acclimatization response to high-altitude hypoxia derives from studies of animal species that are native to lowland environments. Such studies can indicate whether phenotypic plasticity will generally facilitate or impede adaptation to high altitude. Here, we review general mechanisms of physiological acclimatization and genetic adaptation to high-altitude hypoxia in birds and mammals. We evaluate whether the acclimatization response to environmental hypoxia can be regarded generally as a mechanism of adaptive phenotypic plasticity, or whether it might sometimes represent a misdirected response that acts as a hindrance to genetic adaptation. In cases in which the acclimatization response to hypoxia is maladaptive, selection will favor an attenuation of the induced phenotypic change. This can result in a form of cryptic adaptive evolution in which phenotypic similarity between high- and low-altitude populations is attributable to directional selection on genetically based trait variation that offsets environmentally induced changes. The blunted erythropoietic and pulmonary vasoconstriction responses to hypoxia in Tibetan humans and numerous high-altitude birds and mammals provide possible examples of this phenomenon. When lowland animals colonize high-altitude environments, adaptive phenotypic plasticity can mitigate the costs of selection, thereby enhancing prospects for population establishment and persistence. By contrast, maladaptive plasticity has the opposite effect. Thus, insights into the acclimatization response of lowland animals to high-altitude hypoxia can provide a basis for predicting how altitudinal range limits might shift in response to climate change.

Fig. 1.

O₂ is transported from atmospheric air to the mitochondria of tissue cells along a pathway with several diffusive and convective steps. The steps in this O₂ cascade are breathing, O₂ diffusion across the blood–gas interface, circulation of O₂ throughout the body, O₂ diffusion across the blood–tissue interface to the mitochondria, and O₂ utilization to generate ATP by oxidative phosphorylation.

Fig. 2.

The ventilatory response to environmental hypoxia causes a secondary loss of CO₂, and the resulting hypocapnia (low arterial CO₂ tension) and alkalosis (high arterial pH) inhibit breathing. As a result, the hypoxic ventilatory response (HVR) when CO₂ is experimentally maintained (isocapnia, white symbols) is higher than in the environmentally realistic situation when CO₂ is uncontrolled and allowed to fall (poikilocapnia, filled symbols). However, bar-headed geese (orange triangles) are less sensitive to hypocapnia than are low-altitude birds, and thus exhibit an enhanced ventilatory response to acute environmental hypoxia (gray arrow). This is reflected by a higher poikilocapnic HVR in bar-headed geese than in pekin ducks (green squares) but a similar isocapnic HVR. Data are means ± s.e.m., modified from Scott and Milsom (Scott and Milsom, 2007). 1 Torr≈133 Pa.

Fig. 3.

Schematic illustration of blood O₂ transport. (A) O₂-equilibrium curve under physiochemical conditions prevailing in arterial blood (a, solid curve, open symbol) and venous blood (v, dashed curve, closed symbol). The x-axis measures blood P_O2 and the y-axis measures blood O₂ content. Ca_O2–Cv_O2 denotes the arterial–venous difference in O₂ content, Pa_O2–Pv_O2, denotes the corresponding difference in P_O2, βb_O2 denotes the blood O₂ capacitance coefficient (see text for details), denotes cardiac output, and denotes the rate of O₂ consumption. (B) The area of the rectangle is proportional to total O₂ consumption, which can be enhanced by increasing and/or by increasing the βb_O2. Increases in the βb_O2 produce a corresponding increase in Ca_O2–Cv_O2 through shifts in the shape or position of the O₂-equilibrium curve.

Fig. 4.

Odds ratios (OR) for stillbirths (A), preterm births (B) and small-for-gestational-age (SGA) births (C) as a function of maternal Hb concentration. Data are compiled from 37,377 women residing at low (150 m) and high (>3000 m) altitudes (2003–2006) (modified from Gonzales et al., 2009).

Fig. 5.

The diffusion capacity for O₂ is enhanced in the flight muscle of the bar-headed goose, a species that lives at elevation and migrates over the Himalayas at extremely high altitudes. This is accomplished by an increase in capillarity and a redistribution of mitochondria towards the cell membrane. (A) Histological staining for alkaline phosphatase activity identifies abundant capillaries in the pectoralis muscle of a bar-headed goose (scale bar: 50 μm). (B) Transmission electron micrograph of a fast-oxidative muscle fiber in a bar-headed goose showing the abundant subsarcolemmal mitochondria (arrow) and the less common intermyofibrillar mitochondria (arrowhead) (scale bar: 5 μm). See Scott et al. (Scott et al., 2009a) for details.