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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
Abstract 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 (Peromyscus maniculatus) in response to hypoxia exposure at different stages of development. In highland deer mice, developmental plasticity in diaphragm function may mediate changes in several respiratory traits that influence aerobic metabolism and performance under hypoxia. We generated RNAseq data from diaphragm tissue of adult deer mice exposed to (1) life‐long hypoxia (before conception to adulthood), (2) post‐natal hypoxia (birth to adulthood), (3) adult hypoxia (6–8 weeks only during adulthood) or (4) normoxia. We found five suites of co‐regulated genes that are differentially expressed in response to hypoxia, but the patterns of differential expression depend on the developmental timing of exposure. We also identified four transcriptional modules that are associated with important respiratory traits. Many of the genes in these transcriptional modules bear signatures of altitude‐related selection, providing an indirect line of evidence that observed changes in gene expression may be adaptive in hypoxic environments. Our results demonstrate the importance of developmental stage in determining the phenotypic response to environmental stressors.
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- 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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