Andrew D. Beale, Matthew J. Christmas, Nina M. Rzechorzek, Andrei Mihut, Aiwei Zeng, Christopher Ellis, Nathan R. James, Nicola J. Smyllie, Violetta Pilorz, Rose Richardson, Mads F. Bertelsen, Shaline V. Fazal, Zanna Voysey, Kevin Moreau, Jerry Pelletier, Priya Crosby, Sew Y. Peak-Chew, Rachel S. Edgar, Madeline A. Lancaster, Roelof A. Hut, John S. O’Neill
Early mammals were nocturnal while dinosaurs dominated the daytime. Mammalian transition to daytime activity accelerated after the Cretaceous-Paleogene extinction, but the underlying mechanisms remain unclear. We identified a conserved cell-intrinsic, thermodynamic mechanism that likely facilitated this shift. In cells from diurnal mammals, protein synthesis, phosphorylation, and circadian timing were less sensitive to temperature changes than were cells from nocturnal mammals. Comparative genomics revealed accelerated evolution within essential signaling pathways, including mechanistic target of rapamycin (mTOR), that increase the robustness of diurnal cellular clocks to thermal and osmotic perturbation. In nocturnal mice, mTOR inhibition shifted cells, tissues, and behavior toward diurnal activity. These findings uncover a genetic and biochemical basis for nocturnal-diurnal switching, emphasizing how cellular signaling networks can encode complex phenotypes such as temporal niche selection.