Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 109, Issue 22, Pages 8635-8640Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1120523109
Keywords
functional genomics; RNA-seq; thermoregulation; transcriptomics
Categories
Funding
- National Institutes of Health/National Heart Lung and Blood Institute [R01 HL087216, HL087216-S1]
- National Science Foundation [IOS-0949931]
- National Sciences and Engineering Research Council of Canada
- Division Of Integrative Organismal Systems
- Direct For Biological Sciences [0949931] Funding Source: National Science Foundation
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In response to hypoxic stress, many animals compensate for a reduced cellular O-2 supply by suppressing total metabolism, thereby reducing O-2 demand. For small endotherms that are native to high-altitude environments, this is not always a viable strategy, as the capacity for sustained aerobic thermogenesis is critical for survival during periods of prolonged cold stress. For example, survivorship studies of deer mice (Peromyscus maniculatus) have demonstrated that thermogenic capacity is under strong directional selection at high altitude. Here, we integrate measures of whole-organism thermogenic performance with measures of metabolic enzyme activities and genomic transcriptional profiles to examine the mechanistic underpinnings of adaptive variation in this complex trait in deer mice that are native to different elevations. We demonstrate that highland deer mice have an enhanced thermogenic capacity under hypoxia compared with lowland conspecifics and a closely related lowland species, Peromyscus leucopus. Our findings suggest that the enhanced thermogenic performance of highland deer mice is largely attributable to an increased capacity to oxidize lipids as a primary metabolic fuel source. This enhanced capacity for aerobic thermogenesis is associated with elevated activities of muscle metabolic enzymes that influence flux through fatty-acid oxidation and oxidative phosphorylation pathways in high-altitude deer mice and by concomitant changes in the expression of genes in these same pathways. Contrary to predictions derived from studies of humans at high altitude, our results suggest that selection to sustain prolonged thermogenesis under hypoxia promotes a shift in metabolic fuel use in favor of lipids over carbohydrates.
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