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Parallel Measurement of Circadian Clock Gene Expression and Hormone Secretion in Human Primary Cell Cultures
Published on: November 11, 2016
A cellular basis for the mammalian nocturnal-diurnal switch
Andrew D Beale1, Matthew J Christmas2, Nina M Rzechorzek1,3
1MRC Laboratory of Molecular Biology, Cambridge, UK.
Mammals shifted from nocturnal to diurnal activity after dinosaur extinction due to cellular mechanisms making their biological clocks more heat-tolerant. mTOR pathway inhibition in nocturnal mice promoted daytime activity, revealing a genetic basis for temporal niche selection.
Area of Science:
- Evolutionary Biology
- Chronobiology
- Cellular Signaling
Background:
- Early mammals were primarily nocturnal, while dinosaurs occupied diurnal niches.
- The transition of mammals to diurnal activity post-Cretaceous-Paleogene extinction lacks clear mechanistic explanations.
- Understanding the cellular basis of temporal niche selection is crucial for evolutionary studies.
Purpose of the Study:
- To identify the cell-intrinsic mechanisms underlying the mammalian shift from nocturnal to diurnal activity.
- To investigate the role of thermodynamic properties in cellular clocks during this evolutionary transition.
- To explore the genetic and signaling pathways involved in regulating diurnal versus nocturnal behavior.
Main Methods:
- Comparative genomics to identify accelerated evolution in signaling pathways.
- Analysis of protein synthesis, phosphorylation, and circadian timing sensitivity to temperature in cells from diurnal and nocturnal mammals.
- Pharmacological inhibition of the mechanistic target of rapamycin (mTOR) pathway in nocturnal mice.
Main Results:
- Cells from diurnal mammals exhibit reduced sensitivity of protein synthesis, phosphorylation, and circadian timing to temperature fluctuations compared to nocturnal mammals.
- Comparative genomics revealed accelerated evolution in key signaling pathways, notably mTOR, enhancing cellular clock robustness.
- Inhibition of mTOR in nocturnal mice induced a shift towards diurnal activity at cellular, tissue, and behavioral levels.
Conclusions:
- A conserved, cell-intrinsic thermodynamic mechanism involving temperature-robust cellular clocks facilitated the mammalian shift to diurnal activity.
- Accelerated evolution in signaling pathways like mTOR provides a genetic and biochemical basis for adapting temporal niches.
- Cellular signaling networks play a critical role in encoding complex phenotypes such as temporal niche selection.
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