Journal
MOLECULAR BIOLOGY AND EVOLUTION
Volume 32, Issue 8, Pages 1962-1976Publisher
OXFORD UNIV PRESS
DOI: 10.1093/molbev/msv076
Keywords
capillarity; hypoxia adaptation; muscle fiber type; oxygen transport; physiological genomics; RNA-seq
Funding
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- National Institutes of Health [HL087216]
- National Science Foundation [IOS-1354934, IOS-1354390]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL087216] Funding Source: NIH RePORTER
- Division Of Integrative Organismal Systems [1354390, 1354934] Funding Source: National Science Foundation
Ask authors/readers for more resources
At high-altitude, small mammals are faced with the energetic challenge of sustaining thermogenesis and aerobic exercise in spite of the reduced O-2 availability. Under conditions of hypoxic cold stress, metabolic demands of shivering thermogenesis and locomotion may require enhancements in the oxidative capacity and O-2 diffusion capacity of skeletal muscle to compensate for the diminished tissue O-2 supply. We used common-garden experiments involving highland and lowland deer mice (Peromyscus maniculatus) to investigate the transcriptional underpinnings of genetically based population differences and plasticity in muscle phenotype. We tested highland and lowland mice that were sampled in their native environments as well as lab-raised F1 progeny of wild-caught mice. Experiments revealed that highland natives had consistently greater oxidative fiber density and capillarity in the gastrocnemius muscle. RNA sequencing analyses revealed population differences in transcript abundance for 68 genes that clustered into two discrete transcriptional modules, and a large suite of transcripts (589 genes) with plastic expression patterns that clustered into five modules. The expression of two transcriptional modules was correlated with the oxidative phenotype and capillarity of the muscle, and these phenotype-associated modules were enriched for genes involved in energy metabolism, muscle plasticity, vascular development, and cell stress response. Although most of the individual transcripts that were differentially expressed between populations were negatively correlated with muscle phenotype, several genes involved in energy metabolism (e.g., Ckmt1, Ehhadh, Acaa1a) and angiogenesis (Notch4) were more highly expressed in highlanders, and the regulators of mitochondrial biogenesis, PGC-1 alpha (Ppargc1a) and mitochondrial transcription factor A (Tfam), were positively correlated with muscle oxidative phenotype. These results suggest that evolved population differences in the oxidative capacity and capillarity of skeletal muscle involved expression changes in a small suite of coregulated genes.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available