Development of homeothermic endothermy is delayed in high-altitude native deer mice ( Peromyscus maniculatus)

Abstract

Altricial mammals begin to independently thermoregulate during the first few weeks of postnatal development. In wild rodent populations, this is also a time of high mortality (50–95%), making the physiological systems that mature during this period potential targets for selection. High altitude (HA) is a particularly challenging environment for small endotherms owing to unremitting low O 2 and ambient temperatures. While superior thermogenic capacities have been demonstrated in adults of some HA species, it is unclear if selection has occurred to survive these unique challenges early in development. We used deer mice ( Peromyscus maniculatus ) native to high and low altitude (LA), and a strictly LA species ( Peromyscus leucopus ), raised under common garden conditions, to determine if postnatal onset of endothermy and maturation of brown adipose tissue (BAT) is affected by altitude ancestry. We found that the onset of endothermy corresponds with the maturation and activation of BAT at an equivalent age in LA natives, with 10-day-old pups able to thermoregulate in response to acute cold in both species. However, the onset of endothermy in HA pups was substantially delayed (by approx. 2 days), possibly driven by delayed sympathetic regulation of BAT. We suggest that this delay may be part of an evolved cost-saving measure to allow pups to maintain growth rates under the O 2 -limited conditions at HA.

Distinct Mechanisms Underlie Developmental Plasticity and Adult Acclimation of Thermogenic Capacity in High-Altitude Deer Mice

“…There can be strong directional selection for increased thermogenic V̇O 2max at high altitude ( Hayes and O’Connor, 1999 ), which has led to evolved increases in thermogenic V̇O 2max in hypoxia in high-altitude deer mice compared to low-altitude deer mice and white-footed mice ( P. leucopus , a congeneric species that is restricted to low altitudes; Cheviron et al, 2012 , 2013 , 2014 ; Lui et al, 2015 ; Tate et al, 2017 , 2020 ). Differences in thermogenic V̇O 2max and in various respiratory and metabolic traits that underlie it become apparent ~2–3 weeks after birth in comparisons between high- and low-altitude mice raised in normoxia ( Robertson et al, 2019 ; Robertson and McClelland, 2019 ; Ivy et al, 2020 ; West et al, 2021a ). However, although the effects of adult acclimation to hypoxia on thermogenic V̇O 2max and its underlying determinants have been described ( Lui et al, 2015 ; Lau et al, 2017 ; Tate et al, 2017 , 2020 ), and life-long exposure to high altitude has been shown to increase thermogenic V̇O 2max ( Chappell et al, 2007 ), the specific effects of hypoxia exposure during pre-natal and post-natal development has not been resolved.…”

Gene regulatory changes underlie developmental plasticity in respiration and aerobic performance in highland deer mice

“…The enhanced aerobic performance under hypoxia is associated with increased survivorship in free‐ranging mice at high elevation (Hayes & O'Connor, 1999) and is associated with plastic and genetically based modifications across the O 2 transport pathway (Ivy & Scott, 2015; Schweizer et al, 2019; Schweizer et al, 2021; Storz et al, 2019; Storz & Cheviron, 2021; Storz & Scott, 2019). Research into the ontogeny of these differences has only just begun, but some components of the unique physiology of highlanders are clearly manifest within the first few weeks of life (e.g., onset of endothermy, increased blood‐O 2 affinity, development of hypoxic ventilatory response; Ivy et al, 2020, 2021; Robertson et al, 2019; Velotta et al, 2020). The plastic responses to hypoxia also differ between highland and lowland mice.…”

Evolved reductions in body temperature and the metabolic costs of thermoregulation in deer mice native to high altitude

“…Whether high-altitude deer mice have also reduced the routine demands for O 2 and metabolic fuels is less clear, but such reductions could be highly advantageous when considering that in some instances food availability may also be limited at high altitudes [37]. The ontogenetic development of endothermy is delayed in highaltitude deer mice [38][39][40], suggesting that metabolic demands of thermogenesis are reduced in early post-natal life stages. Whether they also exhibit strategies to reduce the metabolic demands of thermogenesis and body temperature regulation in later life remains unresolved.…”