Adaptive Modifications of Muscle Phenotype in High-Altitude Deer Mice Are Associated with Evolved Changes in Gene Regulation

Graham R. Scott, Todd S. Elogio, Mikaela A. Lui, Jay F Storz, Zachary A. Cheviron

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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-1α (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.

Original languageEnglish (US)
Pages (from-to)1962-1976
Number of pages15
JournalMolecular biology and evolution
Volume32
Issue number8
DOIs
StatePublished - Aug 1 2015

Fingerprint

Peromyscus
deer
phenotype
Capillary Action
muscle
Phenotype
capillarity
Muscles
muscles
gene
Skeletal Muscle
Thermogenesis
Genes
highlands
genes
Energy Metabolism
Population
heat production
energy metabolism
skeletal muscle

Keywords

  • RNA-seq
  • capillarity
  • hypoxia adaptation
  • muscle fiber type
  • oxygen transport
  • physiological genomics

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics

Cite this

Adaptive Modifications of Muscle Phenotype in High-Altitude Deer Mice Are Associated with Evolved Changes in Gene Regulation. / Scott, Graham R.; Elogio, Todd S.; Lui, Mikaela A.; Storz, Jay F; Cheviron, Zachary A.

In: Molecular biology and evolution, Vol. 32, No. 8, 01.08.2015, p. 1962-1976.

Research output: Contribution to journalArticle

Scott, Graham R. ; Elogio, Todd S. ; Lui, Mikaela A. ; Storz, Jay F ; Cheviron, Zachary A. / Adaptive Modifications of Muscle Phenotype in High-Altitude Deer Mice Are Associated with Evolved Changes in Gene Regulation. In: Molecular biology and evolution. 2015 ; Vol. 32, No. 8. pp. 1962-1976.
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