Dataset Information

Geographic variation in epigenetic responses to hypoxia in deer mice (Peromyscus maniculatus) distributed along an elevational gradient

ABSTRACT: Spatially varying environments can pose distinct costs and benefits on traits under selection, such that a beneficial trait in one environment may be counter-productive in another. As an example, lowland and highland Peromyscus maniculatus populations display divergent, locally adapted physiological mechanisms shaped by altitudinal differences in oxygen availability. Particularly, lowland mice leverage ancestral plasticity derived from acute episodic bouts of low internal oxygen triggered by causes such as blood loss, anemia or tissue ischemia. These responses can be maladaptive under persistent low-oxygen conditions, as they could lead to physiological complications such as pulmonary hypertension. Therefore, highland ancestry is associated with traits promoting chronic hypoxia tolerance. Given each population’s distinct adaptive histories and reliance on plasticity for hypoxia tolerance, we hypothesized that upon hypoxia exposure lowland mice would have a more robust epigenetic response, driving trait plasticity, than highland mice. Using DNA methylation data collected from left ventricle tissues, we show that upon hypoxia exposure, lowland mice can chemically modulate the epigenetic landscape to a greater extent than highland mice, especially at key hypoxia-relevant genes such as Egln3, a regulator of Epas1- a gene frequently targeted for positive selection at high elevation. In addition, lowland mice show greater enrichment of DNA methylation change concentrated at hypoxia-relevant biological pathways, particularly those related to Notch ligands. These findings exemplify each population’s distinct reliance on molecular plasticity driven by their unique evolutionary histories.

ORGANISM(S): Peromyscus maniculatus

PROVIDER: GSE270202 | GEO | 2025/04/30

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Skeletal muscle is the largest tissue in the body and mainly relies on mitochondrial oxidative metabolism for sustainable ATP production. Reduced oxygen availability, also known as hypoxia, can be caused by high altitude or pathology and impacts mitochondria. Whereas long-term hypoxia results in increased reliance on glycolysis, reduced fatty acid oxidation and a decreased skeletal muscle mass, the in vivo mechanisms of adaptation of skeletal muscle to acute hypoxia remain elusive. Therefore, we aimed to provide an integrated description of the response of the M. gastrocnemius to acute hypoxia. Fasted male C57BL/6JOlaHsd mice were exposed to 12% oxygen representing normobaric hypoxia versus 21% oxygen (normoxia) for six hours (n=12 mice per group). Whole-body energy metabolism and the transcriptome response of the M. gastrocnemius mice was analyzed and confirmed by acylcarnitine determination and RT-qPCR. On whole-body level, six hours of hypoxia reduced energy expenditure, increased blood glucose and tended to further decrease the respiratory exchange ratio (RER). Whole genome transcriptome analysis revealed upregulation of the FOXO signalling pathway including an increased expression of Trib3, which was positively correlated with blood glucose. Apart from upregulation of Cpt1a, which negatively correlated with the RER, and SLC25a25 (Cact), fatty acid β-oxidation was not regulated. Together with significantly increased muscle C14 and C16-acylcarnitines this supports no increased fatty acid catabolism in muscle. In addition, the hypoxia-induced FOXO activation could also be connected to altered gene profiles related to fiber type switching, extracellular matrix remodelling, muscle differentiation and the denervation of neuromuscular junctions (NMJ). Conclusively, our results suggest that an acute, six hours exposure of mice to hypoxia impacts M. gastrocnemius via FOXO1, initiating alterations in skeletal muscle that may ultimately contribute to tissue remodelling. This supports an early role of hypoxia in tissue alterations in hypoxia-associated conditions such as aging and obesity. The observed impact of hypoxia on denervated NMJ is novel and warrants further investigation.

Dataset Information

Geographic variation in epigenetic responses to hypoxia in deer mice (Peromyscus maniculatus) distributed along an elevational gradient

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets