ABSTRACT Physiological systems often have emergent properties but the effects of genetic variation on physiology are often unknown, which presents a major challenge to understanding the mechanisms of phenotypic evolution. We investigated whether genetic variants in haemoglobin (Hb) that contribute to high-altitude adaptation in deer mice (Peromyscus maniculatus) are associated with evolved changes in the control of breathing. We created F2 inter-population hybrids of highland and lowland deer mice to test for phenotypic associations of α- and β-globin variants on a mixed genetic background. Hb genotype had expected effects on Hb–O2 affinity that were associated with differences in arterial O2 saturation in hypoxia. However, high-altitude genotypes were also associated with breathing phenotypes that should contribute to enhancing O2 uptake in hypoxia. Mice with highland α-globin exhibited a more effective breathing pattern, with highland homozygotes breathing deeper but less frequently across a range of inspired O2, and this difference was comparable to the evolved changes in breathing pattern in deer mouse populations native to high altitude. The ventilatory response to hypoxia was augmented in mice that were homozygous for highland β-globin. The association of globin variants with variation in breathing phenotypes could not be recapitulated by acute manipulation of Hb–O2 affinity, because treatment with efaproxiral (a synthetic drug that acutely reduces Hb–O2 affinity) had no effect on breathing in normoxia or hypoxia. Therefore, adaptive variation in Hb may have unexpected effects on physiology in addition to the canonical function of this protein in circulatory O2 transport.
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Gene regulatory changes underlie developmental plasticity in respiration and aerobic performance in highland deer mice
Phenotypic plasticity can play an important role in the ability of animals to tolerate environmental stress, but the nature and magnitude of plastic responses are often specific to the developmental timing of exposure. Here, we examine changes in gene expression in the diaphragm of highland deer mice (
- Award ID(s):
- 2114465
- PAR ID:
- 10420733
- Publisher / Repository:
- Wiley-Blackwell
- Date Published:
- Journal Name:
- Molecular Ecology
- Volume:
- 32
- Issue:
- 13
- ISSN:
- 0962-1083
- Format(s):
- Medium: X Size: p. 3483-3496
- Size(s):
- p. 3483-3496
- Sponsoring Org:
- National Science Foundation
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null (Ed.)Population genomic studies of humans and other animals at high altitude have generated many hypotheses about the genes and pathways that may have contributed to hypoxia adaptation. Future advances require experimental tests of such hypotheses to identify causal mechanisms. Studies to date illustrate the challenge of moving from lists of candidate genes to the identification of phenotypic targets of selection, as it can be difficult to determine whether observed genotype–phenotype associations reflect causal effects or secondary consequences of changes in other traits that are linked via homeostatic regulation. Recent work on high-altitude models such as deer mice has revealed both plastic and evolved changes in respiratory, cardiovascular, and metabolic traits that contribute to aerobic performance capacity in hypoxia, and analyses of tissue-specific transcriptomes have identified changes in regulatory networks that mediate adaptive changes in physiological phenotype. Here we synthesize recent results and discuss lessons learned from studies of high-altitude adaptation that lie at the intersection of genomics and physiology.more » « less
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Abstract A key question in biology concerns the extent to which distributional range limits of species are determined by intrinsic limits of physiological tolerance. Here, we use common‐garden data for wild rodents to assess whether species with higher elevational range limits typically have higher thermogenic capacities in comparison to closely related lowland species. Among South American leaf‐eared mice (genus
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