Molecular Variation in Thermoregulatory Adaptation in Rodents

AbstractEndothermic homeothermy, a key adaptation in mammals and birds, enables survival across diverse environments, albeit at significant energetic costs. Some mammals mitigate these costs through flexible thermoregulation, alternating homeothermy with daily heterothermy or hibernation in response to environmental variability. We hypothesize that flexible thermoregulators have evolved adaptive molecular changes in thermoregulatory genes to enhance responsiveness to environmental change. To test this, we analyzed 54 thermoregulation-associated genes in 21 rodent species, traditionally classified as homeothermic, daily heterothermic, or hibernating. Signals of positive selection were identified in 35 genes, many of which were shared among thermoregulatory strategies. Daily heterotherms exhibited stronger selection signals in metabolic and stress-response genes, while hibernators showed selection in homeostasis-related genes. Protein modeling and structural docking analyses revealed that amino acid substitutions in Ucp1 marginally altered predicted folding, likely enhancing thermal stability and acclimation to fluctuating temperatures in daily heterotherms. Hibernators showed increased connectivity in thermoregulatory protein networks, suggesting greater molecular complexity and flexibility. The overlap of positively selected genes in multiple species suggests that thermoregulatory strategies form a continuum rather than discrete categories. Our findings highlight how gene evolution and network connectivity underpin the emergence of thermoregulatory flexibility in mammals, enabling adaptative responses to environmental challenges.