A cellular basis for the mammalian nocturnal-diurnal switch
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.
Authors
- Jerry Pelletier (ORCID: https://orcid.org/0000-0003-1963-6466)
- John S. O’Neill (ORCID: https://orcid.org/0000-0003-2204-6096)
- Zanna J. Voysey (ORCID: https://orcid.org/0000-0002-6980-6059)
- Nicola J. Smyllie (ORCID: https://orcid.org/0000-0002-6324-1421)
- Aiwei Zeng (ORCID: https://orcid.org/0000-0003-0354-2529)
- Andrei Mihut (ORCID: https://orcid.org/0000-0003-4241-2567)
- Nathan R. James (ORCID: https://orcid.org/0000-0003-1147-6285)
- Violetta Pilorz (ORCID: https://orcid.org/0000-0002-8478-1734)
- Rachel S. Edgar (ORCID: https://orcid.org/0000-0002-3348-0851)
- Matthew J. Christmas (ORCID: https://orcid.org/0000-0002-6355-7581)
- Nina M. Rzechorzek (ORCID: https://orcid.org/0000-0003-3209-5019)
- Rose Richardson (ORCID: https://orcid.org/0000-0001-7164-0337)
- Shaline V. Fazal (ORCID: https://orcid.org/0000-0002-2813-4022)
- Priya Crosby (ORCID: https://orcid.org/0000-0002-7532-7708)
- Mads F. Bertelsen (ORCID: https://orcid.org/0000-0001-9201-7499)
- Madeline A. Lancaster (ORCID: https://orcid.org/0000-0003-2324-8853)
- Andrew D. Beale (ORCID: https://orcid.org/0000-0002-2051-0919)
- Roelof A. Hut
- Christopher Ellis
- Sew Y. Peak-Chew
- Kevin Moreau
Institutions
- Uppsala University (SE)
- University of Groningen (NL)
- MRC Laboratory of Molecular Biology (GB)
- University of California, Santa Cruz (US)
- University of Cambridge (GB)
- Science for Life Laboratory (SE)
- The Francis Crick Institute (GB)
- Copenhagen Zoo (DK)
- University of Manchester (GB)
- AstraZeneca (South Korea) (KR)
- AstraZeneca (Poland) (PL)
- Imperial College London (GB)
- McGill University (CA)
- University of Lübeck (DE)
- University of Edinburgh (GB)
Publication Details
- Journal
- Science
- Published
- 2026-02-26
- DOI
- https://doi.org/10.1126/science.ady2822
- Primary Topic
- Circadian rhythm and melatonin
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- AstraZeneca
- Wellcome Trust
- UK Research and Innovation
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Medical Research Council