Animals native to the hypoxic and cold environment at high altitude provide an excellent opportunity to elucidate the integrative mechanisms underlying the adaptive evolution of complex traits. The capacity for aerobic thermogenesis can be a critical determinant of survival for small mammals at high altitude, but the physiological mechanisms underlying the evolution of thermogenic capacity remain unresolved. We examined this issue by comparing high-altitude deer mice (Peromyscus maniculatus) to low-altitude deer mice and white-footed mice (P. leucopus). Mice were bred in captivity and adults were acclimated to each of four treatments: warm (25°C) normoxia; warm hypoxia (12 kPa O₂); cold (5°C) normoxia; or cold hypoxia. Acclimation to hypoxia and/or cold increased thermogenic capacity, but hypoxia acclimation led to much greater increases in thermogenic capacity in highlanders than in lowlanders. The high thermogenic capacity of highlanders was associated with increases in pulmonary O₂ extraction, arterial O₂ saturation, cardiac output, stroke volume, and arterial-venous O₂ difference. These mechanisms underlying the evolution of enhanced thermogenic capacity in highlanders were partially distinct from those underlying the ancestral acclimation responses of lowlanders. Environmental adaptation has thus enhanced phenotypic plasticity and expanded the physiological toolkit for coping with the challenges at high altitude.

Data were collected from Peromyscus mice during acute exposure to cold hypoxic heliox. See publication for a detailed description of the methods used to collect the data.

Not all measurements were made on every individual mouse, as described in the main paper and supplementary materials for the publication.