Environmental hypoxia challenges female reproductive physiology in placental mammals, increasing rates of gestational complications. Adaptation to high elevation has limited many of these effects in humans and other mammals, offering potential insight into the developmental processes that lead to and protect against hypoxia-related gestational complications. However, our understanding of these adaptations has been hampered by a lack of experimental work linking the functional, regulatory, and genetic underpinnings of gestational development in locally adapted populations. Here, we dissect high-elevation adaptation in the reproductive physiology of 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 (
- NSF-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
More Like this
-
more » « less
Peromyscus maniculatus ), a rodent species with an exceptionally broad elevational distribution that has emerged as a model for hypoxia adaptation. Using experimental acclimations, we show that lowland mice experience pronounced fetal growth restriction when challenged with gestational hypoxia, while highland mice maintain normal growth by expanding the compartment of the placenta that facilitates nutrient and gas exchange between gestational parent and fetus. We then use compartment-specific transcriptome analyses to show that adaptive structural remodeling of the placenta is coincident with widespread changes in gene expression within this same compartment. Genes associated with fetal growth in deer mice significantly overlap with genes involved in human placental development, pointing to conserved or convergent pathways underlying these processes. Finally, we overlay our results with genetic data from natural populations to identify candidate genes and genomic features that contribute to these placental adaptations. Collectively, these experiments advance our understanding of adaptation to hypoxic environments by revealing physiological and genetic mechanisms that shape fetal growth trajectories under maternal hypoxia. -
more » « less
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
Phyllotis ), mean thermogenic performance is higher in species with higher elevational range limits, but there is little among‐species variation in the magnitude of plasticity in this trait. In the North American rodent genusPeromyscus , highland deer mice (Peromyscus maniculatus ) have greater thermogenic maximal oxygen uptake () than lowland white‐footed mice (Peromyscus leucopus ) at a level of hypoxia that matches the upper elevational range limit of the former species. In highland deer mice, the enhanced thermogenic in hypoxia is attributable to a combination of evolved and plastic changes in physiological pathways that govern the transport and utilization of O2and metabolic substrates. Experiments withPeromyscus mice also demonstrate that exposure to hypoxia during different stages of development elicits plastic changes in cardiorespiratory traits that improve thermogenic via distinct physiological mechanisms. Evolved differences in thermogenic capacity provide clues about why some species are able to persist in higher‐elevation habitats that lie slightly beyond the tolerable limits of other species. Such differences in environmental tolerance also suggest why some species might be more vulnerable to climate change than others.image -
more » « less
Abstract Background Complex organismal traits are often the result of multiple interacting genes and sub-organismal phenotypes, but how these interactions shape the evolutionary trajectories of adaptive traits is poorly understood. We examined how functional interactions between cardiorespiratory traits contribute to adaptive increases in the capacity for aerobic thermogenesis (maximal O2consumption,
V̇ O2max, during acute cold exposure) in high-altitude deer mice (Peromyscus maniculatus ). We crossed highland and lowland deer mice to produce F2inter-population hybrids, which expressed genetically based variation in hemoglobin (Hb) O2affinity on a mixed genetic background. We then combined physiological experiments and mathematical modeling of the O2transport pathway to examine the links between cardiorespiratory traits andV̇ O2max.Results Physiological experiments revealed that increases in Hb-O2affinity of red blood cells improved blood oxygenation in hypoxia but were not associated with an enhancement in
V̇ O2max. Sensitivity analyses performed using mathematical modeling showed that the influence of Hb-O2affinity onV̇ O2max in hypoxia was contingent on the capacity for O2diffusion in active tissues.Conclusions These results suggest that increases in Hb-O2affinity would only have adaptive value in hypoxic conditions if concurrent with or preceded by increases in tissue O2diffusing capacity. In high-altitude deer mice, the adaptive benefit of increasing Hb-O2affinity is contingent on the capacity to extract O2from the blood, which helps resolve controversies about the general role of hemoglobin function in hypoxia tolerance.
-
more » « less
Key points Small mammals native to high altitude must sustain high rates of thermogenesis to cope with cold. Skeletal muscle is a key site of shivering and non‐shivering thermogenesis, but the importance of mitochondrial plasticity in cold hypoxic environments remains unresolved.
We examined high‐altitude deer mice, which have evolved a high capacity for aerobic thermogenesis, to determine the mechanisms of mitochondrial plasticity during chronic exposure to cold and hypoxia, alone and in combination.
Cold exposure in normoxia or hypoxia increased mitochondrial leak respiration and decreased phosphorylation efficiency and OXPHOS coupling efficiency, which may serve to augment non‐shivering thermogenesis. Cold also increased muscle oxidative capacity, but reduced the capacity for mitochondrial respiration via complex II relative to complexes I and II combined.
High‐altitude mice had a more oxidative muscle phenotype than low‐altitude mice.
Therefore, both plasticity and evolved changes in muscle mitochondria contribute to thermogenesis at high altitude.
Abstract Small mammals native to high altitude must sustain high rates of thermogenesis to cope with cold and hypoxic environments. Skeletal muscle is a key site of shivering and non‐shivering thermogenesis, but the importance of mitochondrial plasticity in small mammals at high altitude remains unresolved. High‐altitude deer mice (
Peromyscus maniculatus ) and low‐altitude white‐footed mice (P. leucopus ) were born and raised in captivity, and chronically exposed as adults to warm (25°C) normoxia, warm hypoxia (12 kPa O2), cold (5°C) normoxia, or cold hypoxia. We then measured oxidative enzyme activities, oxidative fibre density and capillarity in the gastrocnemius, and used a comprehensive substrate titration protocol to examine the function of muscle mitochondria by high‐resolution respirometry. Exposure to cold in both normoxia or hypoxia increased the activities of citrate synthase and cytochrome oxidase. In lowlanders, this was associated with increases in capillary density and the proportional abundance of oxidative muscle fibres, but in highlanders, these traits were unchanged at high levels across environments. Environment had some distinct effects on mitochondrial OXPHOS capacity between species, but the capacity of complex II relative to the combined capacity of complexes I and II was consistently reduced in both cold environments. Both cold environments also increased leak respiration and decreased phosphorylation efficiency and OXPHOS coupling efficiency in both species, which may serve to augment non‐shivering thermogenesis. These cold‐induced changes in mitochondrial function were overlaid upon the generally more oxidative phenotype of highlanders. Therefore, both plasticity and evolved changes in muscle mitochondria contribute to thermogenesis at high altitudes. -
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.more » « less
