Amazing stuff! How mammals became diurnal after nocturnality!
"Early mammals were nocturnal, sleeping during the day while large predators were active. However, after the extinction of dinosaurs, several different lineages of mammals independently transitioned to become active during the day. Exactly how this dramatic change occurred has proved elusive. A new study, published in the journal Science, has revealed a cellular switch which holds the answer. ...
he study looked at how cells from a range of nocturnal (active at night) and diurnal (active in the day) mammals, like humans, respond to environmental signals.
Changes in temperature or osmolarity, as happens to the body throughout the day, caused the cells to respond in opposite ways, including in fundamental cellular functions. This divergence flips the timing of cellular activity, essentially acting as a day/night ‘switch’ at a molecular level.
The researchers pinpointed these differing responses to the mechanistic Target of Rapamycin (mTOR) and With-no-lysine (WNK) kinase pathways, central signalling networks in cells responsible for regulating several key functions, including protein synthesis. This suggested that modification of their activity could enable nocturnal mammals to switch to more diurnal activity.
To explore this hypothesis, the researchers administered diet-based treatments to mice to target the mTOR pathway, as mTOR activity is highly sensitive to nutrient levels.
Once mTOR function was reduced, the mice began behaving more like diurnal animals, shifting their active hours into the daytime. This underlined that mTOR signalling goes beyond influencing metabolism; it also helps dictate when an animal is active. ..."
From the editor's summary and abstract:
"Editor’s summary
When ferocious dinosaurs roamed the earth, it was advantageous for mammals to be nocturnal. After these predators became extinct, many mammals (including the ancestors of humans) switched their daily rhythms to be active during the day. Beale et al. explored changes that might allow animals that retain the same fundamental clock components to make this switch. One cue that influences the timing of cellular clocks is temperature. Cells of nocturnal animals were more sensitive to temperature changes, and their clocks ran faster at higher temperatures. This appeared to reflect differential sensitivity of signaling pathways that regulate rates of protein translation through changes in protein phosphorylation. Inhibition of one pathway containing the protein kinase mTOR (mechanistic target of rapamycin) shifted nocturnal mouse cells toward more diurnal activity. ...
Structured Abstract
INTRODUCTION
The ancestors of modern mammals were strictly nocturnal, avoiding the daytime while dinosaurs dominated. Only after the extinction of nonavian dinosaurs did mammals radiate into daytime niches, meaning that daily physiological rhythms became reversed with respect to the day and night but without any change in the brain’s master circadian clock.
Diurnality evolved multiple times, independently, but can also arise spontaneously in certain nocturnal species under conditions of very low energy balance. No specific neuroanatomical circuit has been demonstrated to function as a nocturnal-diurnal switch in any mammalian lineage, so we tested the hypothesis that this daily biological signal inverter instead has a cell-autonomous basis.
RATIONALE
Circadian timing is intrinsic to most mammalian cells. Daily hormonal cues, such as glucocorticoid and insulin signaling, potently synchronize cellular clocks with each other and the external day:night cycle, with very similar effects on the cellular clocks of diurnal and nocturnal mammals. However, the rates and equilibria of several fundamental biochemical processes were recently revealed to differ markedly between human and mouse cells. We therefore asked whether daily systemic rhythms (temperature, osmolality) that directly affect cellular biochemistry might elicit different effects on the function of diurnal versus nocturnal mammalian cells. To test this, we compared responses of cells and tissues under acute, long-term, and cyclical stimuli at the levels of circadian timing (bioluminescence reporter assays), proteins (proteome), protein modifications (phosphoproteome), and protein synthesis. We used comparative genomics to identify genes evolving with diurnal niche preference, and we perturbed candidate pathways in cells, tissues, and live mice to test causality.
RESULTS
Using daily thermal or osmotic cycles as a tool, we found opposite entrainment of diurnal versus nocturnal cells, reflecting their species’ temporal niche. Mouse and human cells differed not only in the magnitude but also the direction of their response to temperature. Moreover, temperature change evoked opposite shifts in global protein synthesis and phosphorylation between human and mouse cells and implicated differential sensitivity of the mechanistic target of rapamycin (mTOR) and with-no-lysine (WNK) kinase signaling pathways as plausible mediators.
Comparative genomics validated that genes in these pathways show accelerated evolution in diurnal mammals, rendering diurnal cells more robust against perturbations of solvent thermodynamics and consistent with an energy-saving adaptation. Last, manipulation of mTOR signaling in nocturnal mouse cells and tissues and in vivo was sufficient to shift circadian timing toward being more diurnal.
CONCLUSION
We identified a cell-intrinsic, thermodynamic mechanism underlying the mammalian switch between nocturnal and diurnal activity. By linking cellular responses to thermodynamic perturbation with circadian entrainment through genetic alterations in the mTOR and WNK pathways, our findings explain how diurnality could repeatedly evolve in mammals. More broadly, they highlight that even fundamental cellular properties, such as the response to temperature, may differ systematically between species, with profound consequences for circadian biology and temporal niche."
A cellular basis for the mammalian nocturnal-diurnal switch (no public access)
Convergent evolution of cellular clock robustness to perturbation as a route to mammalian diurnality.
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