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

Abstract

An important means of physiological adaptation to environmental hypoxia is an increased oxygen (O2) affinity of the hemoglobin (Hb) that can help secure high O2 saturation of arterial blood. However, the trade-off associated with a high Hb-O2 affinity is that it can compromise O2 unloading in the systemic capillaries. High-altitude deer mice (Peromyscus maniculatus) have evolved an increased Hb-O2 affinity relative to lowland conspecifics, but it is not known whether they have also evolved compensatory mechanisms to facilitate O2 unloading to respiring tissues. Here we investigate the effects of pH (Bohr effect) and temperature on the O2-affinity of high- and low-altitude deer mouse Hb variants, as these properties can potentially facilitate O2 unloading to metabolizing tissues. Our experiments revealed that Bohr factors for the high- and low-altitude Hb variants are very similar in spite of the differences in O2-affinity. The Bohr factors of deer mouse Hbs are also comparable to those of other mammalian Hbs. In contrast, the high- and low-altitude variants of deer mouse Hb exhibited similarly low temperature sensitivities that were independent of red blood cell anionic cofactors, suggesting an appreciable endothermic allosteric transition upon oxygenation. In conclusion, high-altitude deer mice have evolved an adaptive increase in Hb-O2 affinity, but this is not associated with compensatory changes in sensitivity to changes in pH or temperature. Instead, it appears that the elevated Hb-O2 affinity in high-altitude deer mice is compensated by an associated increase in the tissue diffusion capacity of O2 (via increased muscle capillarization), which promotes O2 unloading.

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

“…the independent colonization of high-altitude environments by multiple species) complement insights derived from controlled laboratory experiments. For example, comparative studies have documented that high-altitude rodents often have higher Hb and/or blood O 2 affinities than their lowland relatives (Hall et al, 1936;Bullard et al, 1966;Ostojic et al, 2002;Storz, 2007;Storz et al, 2009Storz et al, , 2010aNatarajan et al, 2013Natarajan et al, , 2015aJensen et al, 2016), and these observations complement the results of experiments demonstrating that increases in blood-O 2 affinity enhance tissue O 2 delivery and measures of physiological performance in rodents subjected to environmental hypoxia (Eaton et al, 1974;Turek et al, 1978a,b;Chappell and Snyder, 1984). Such consilience of evidence from comparative and experimental studies can greatly strengthen conclusions about the adaptive significance of evolutionary changes in Hb-O 2 affinity.…”

“…This latter 'KCl+DPG' treatment is most relevant to in vivo conditions in mammalian red blood cells, but measurements of O 2 affinity under each of the four standardized treatments can provide insights into the functional mechanism responsible for observed differences in P 50 (KCl+DPG) . (A) Comparison between Hb variants of high-and low-altitude deer mice, Peromyscus maniculatus, from the Rocky Mountains and Great Plains, respectively [data from Natarajan et al, 2015a; for additional details, see Storz et al (2009Storz et al ( , 2010a; Jensen et al (2016)]. (B) Comparison between Hbs of the high-altitude American pika (Ochotona princeps) and the low-altitude collared pika (O. collaris) (data from Tufts et al, 2015).…”

The Greenland shark Somniosus microcephalus—Hemoglobins and ligand-binding properties

“…microcephalus Hbs, indicating that binding of negatively-charged ATP to the low-affinity conformation enhances H + uptake. For comparison, the Bohr coefficient of human adult HbA in the presence of Cl - is around -0.50 in the pH range of 7.0–7.4 [35, 37, 71]. S .…”

Alteration of the α1β2/α2β1 subunit interface contributes to the increased hemoglobin-oxygen affinity of high-altitude deer mice

“…Populations of deer mice that are native to high-altitudes in the Rocky Mountains have evolved a genetically based increase in hemoglobin-oxygen affinity relative to lowland conspecifics in the prairie grassland. The hemoglobin of the highland mice has a higher intrinsic oxygen-affinity, and this affinity difference is further accentuated in the presence of chloride ions and 2,3-disphophoglycrate (DPG)[15–19]. The most common hemoglobin variants of high- and low-altitude deer mice are distinguished by a total of 12 amino acid substitutions–eight in the in the α subunit and four in the β subunit (Fig 1A).…”

“…The most common hemoglobin variants of high- and low-altitude deer mice are distinguished by a total of 12 amino acid substitutions–eight in the in the α subunit and four in the β subunit (Fig 1A). The oxygenation properties of these alternative variants are well-characterized [15–19], but the structural basis of the observed differences in oxygen affinity has not been fully elucidated.…”