A cellular basis for the mammalian nocturnal-diurnal switch

Mammalian colonization of daytime niches accelerated after the Cretaceous-Paleogene extinction. Diurnality subsequently evolved multiple times independently, but underlying mechanisms remain unclear. We identified a conserved cell-intrinsic signal inversion that may have facilitated transitions from nocturnality to diurnality. Diurnal and nocturnal mammalian cells respond oppositely to temperature and osmotic cycles, mirroring species’ activity patterns. Cells exhibited differential global responses to temperature changes, including the phosphoproteome and protein synthesis. Differences in mechanistic Target of Rapamycin (mTOR) signaling contribute to the inversion, with diurnal mammals evolutionarily converging on modifications to mTOR and With-no-lysine (WNK) kinase pathways. Treatments that reduced mTOR activity induced nocturnal-to-diurnal shifting at cellular, tissue, and organismal levels. Therefore, mTOR signaling integrates energetic state with environmental signals to help tune physiology to different temporal niches.