Dataset Information

The adaptive benefit of evolved increases in hemoglobin-O₂ affinity is contingent on tissue O₂ diffusing capacity in high-altitude deer mice.

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 O₂ consumption, V̇O₂max, during acute cold exposure) in high-altitude deer mice (Peromyscus maniculatus). We crossed highland and lowland deer mice to produce F₂ inter-population hybrids, which expressed genetically based variation in hemoglobin (Hb) O₂ affinity on a mixed genetic background. We then combined physiological experiments and mathematical modeling of the O₂ transport pathway to examine the links between cardiorespiratory traits and V̇O₂max.

Results

Physiological experiments revealed that increases in Hb-O₂ affinity of red blood cells improved blood oxygenation in hypoxia but were not associated with an enhancement in V̇O₂max. Sensitivity analyses performed using mathematical modeling showed that the influence of Hb-O₂ affinity on V̇O₂max in hypoxia was contingent on the capacity for O₂ diffusion in active tissues.

Conclusions

These results suggest that increases in Hb-O₂ affinity would only have adaptive value in hypoxic conditions if concurrent with or preceded by increases in tissue O₂ diffusing capacity. In high-altitude deer mice, the adaptive benefit of increasing Hb-O₂ affinity is contingent on the capacity to extract O₂ from the blood, which helps resolve controversies about the general role of hemoglobin function in hypoxia tolerance.

SUBMITTER: Wearing OH

PROVIDER: S-EPMC8218429 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:At high-altitude, small mammals are faced with the energetic challenge of sustaining thermogenesis and aerobic exercise in spite of the reduced O2 availability. Under conditions of hypoxic cold stress, metabolic demands of shivering thermogenesis and locomotion may require enhancements in the oxidative capacity and O2 diffusion capacity of skeletal muscle to compensate for the diminished tissue O2 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? (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.

Dataset Information

The adaptive benefit of evolved increases in hemoglobin-O₂ affinity is contingent on tissue O₂ diffusing capacity in high-altitude deer mice.

Background

Results

Conclusions

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

The adaptive benefit of evolved increases in hemoglobin-O2 affinity is contingent on tissue O2 diffusing capacity in high-altitude deer mice.

Background

Results

Conclusions

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

The adaptive benefit of evolved increases in hemoglobin-O₂ affinity is contingent on tissue O₂ diffusing capacity in high-altitude deer mice.