Phenotypic plasticity in blood-oxygen transport in highland and lowland deer mice

Abstract

SUMMARYIn vertebrates living at high altitude, arterial hypoxemia may be ameliorated by reversible changes in the oxygen-carrying capacity of the blood (regulated by erythropoiesis) and/or changes in blood-oxygen affinity (regulated by allosteric effectors of hemoglobin function). These hematological traits often differ between taxa that are native to different elevational zones, but it is often unknown whether the observed physiological differences reflect fixed, genetically based differences or environmentally induced acclimatization responses (phenotypic plasticity). Here, we report measurements of hematological traits related to blood-O 2 transport in populations of deer mice (Peromyscus maniculatus) that are native to high-and low-altitude environments. We conducted a common-garden breeding experiment to assess whether altitude-related physiological differences were attributable to developmental plasticity and/or physiological plasticity during adulthood. Under conditions prevailing in their native habitats, high-altitude deer mice from the Rocky Mountains exhibited a number of pronounced hematological differences relative to low-altitude conspecifics from the Great Plains: higher hemoglobin concentrations, higher hematocrits, higher erythrocytic concentrations of 2,3-diphosphoglycerate (an allosteric regulator of hemoglobin-oxygen affinity), lower mean corpuscular hemoglobin concentrations and smaller red blood cells. However, these differences disappeared after 6weeks of acclimation to normoxia at low altitude. The measured traits were also indistinguishable between the F 1 progeny of highland and lowland mice, indicating that there were no persistent differences in phenotype that could be attributed to developmental plasticity. These results indicate that the naturally occurring hematological differences between highland and lowland mice are environmentally induced and are largely attributable to physiological plasticity during adulthood. Supplementary material available online at

Bohr effect and temperature sensitivity of hemoglobins from highland and lowland deer mice

“…In conclusion, adaptive modifications of the oxygenation properties of deer mouse Hbs do not affect the magnitude of the Bohr effect, indicating that O 2 unloading at high-altitude is instead facilitated by an increased muscle capillary density, and possibly also by plastic changes in hematocrit, Hb concentration, and intraerythrocytic DPG concentration that increase blood-O 2 carrying capacity (Tufts et al 2013; Lui et al 2015). Furthermore, the low temperature effect on Hb-O 2 affinity, which is comparable to that of temperature-insensitive ruminant Hbs, suggests that O 2 delivery to extremities that are below the body core temperature may be facilitated by a lower heat of oxygenation of the Hb, as reported in polar mammals (Weber and Campbell 2011).…”

“…For example, high-altitude deer mice have evolved significantly higher muscle capillary densities relative to lowland mice (Lui et al 2015; Scott et al 2015), a change which should increase the O 2 diffusion capacity, thereby enhancing aerobic capacity under hypoxia (Wagner 1996; Scott and Milsom 2006). Moreover, deer mice exhibit plasticity in a number of hematological traits such as hematocrit, Hb concentration, and the intraerythrocytic concentration of DPG that can potentially enhance blood-O 2 carrying capacity in response to hypoxia (Tufts et al 2013; Lui et al 2015). Thus, it appears that genetic adaptation to high-altitude in deer mice involves an evolved increase in Hb-O 2 affinity, which maximizes pulmonary O 2 loading, in conjunction with an evolved increase in tissue diffusion capacity of O 2 (via increased muscle capillarization) that should promote O 2 unloading.…”

Hemoglobin–oxygen affinity in high-altitude vertebrates: is there evidence for an adaptive trend?

“…In mammals that have acclimatized to chronic hypoxia, the seemingly maladaptive increase in red cell [DPG] may represent a miscued response to environmental hypoxia in species whose ancestors evolved in a lowland environment (Storz et al, 2010b;Tufts et al, 2013). In contrast to mammals, teleost fishes typically respond to environmental hypoxia by reducing red cell concentrations of nucleotide triphosphates such as ATP and GTP, thereby increasing Hb-O 2 affinity to enhance O 2 uptake in the gills (Weber, 1996;Jensen et al, 1998;Val, 2000;Nikinmaa, 2001).…”

Genetically based low oxygen affinities of felid hemoglobins: lack of biochemical adaptation to high-altitude hypoxia in the snow leopard

“…It is clear that the loss of DPG sensitivity caused by the β2His→Phe substitution effectively eliminates a mechanism of phenotypic plasticity that plays a well-documented role in the acclimatization response to hypoxia in many other eutherian mammals (MacArthur, 1984;Tufts et al, 2013;Weber and Fago, 2004). The reduced intrinsic O 2 affinity of feline Hb clearly compensates for the loss of DPG-mediated regulation of O 2 binding, otherwise the constitutively elevated blood-O 2 affinity would impair O 2 unloading to the cells of respiring tissues.…”