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bioRxiv · 10.1101/2024.04.24.590752

The reindeer circadian clock is rhythmic and temperature-compensated but shows evidence of weak coupling between the secondary and core molecular clock loops

Appenroth, D.·Ravuri, C. S.·Torppa, S. K.·Wood, S. H.·Hazlerigg, D. G.·West, A. C.
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Abstract

Circadian rhythms synchronize the internal physiology of animals allowing them to anticipate daily changes in their environment. Arctic habitats may diminish the selective advantages of circadian rhythmicity by relaxing daily rhythmic environmental constraints, presenting a valuable opportunity to study the evolution of circadian rhythms. In reindeer, circadian control of locomotor activity and melatonin release is weak or absent, and the molecular clockwork is reportedly non-functional. Here we present new evidence that the circadian clock in cultured reindeer fibroblasts is rhythmic and temperature-compensated. Compared to mouse fibroblasts, however, reindeer fibroblasts have a short free-running period, and temperature cycles have an atypical impact on clock gene regulation. In reindeer cells, Per2 and Bmal1 reporters show rapid responses to temperature cycles, with a disintegration of their normal antiphasic relationship. The antiphasic Per2 - Bmal1 relationship re-emerges immediately after release from temperature cycles, but without complete temperature entrainment and with a marked decline in circadian amplitude. Experiments using Bmal1 promoter reporters with mutated RORE sites showed that a reindeer-like response to temperature cycles can be mimicked in mouse or human cell lines by decoupling Bmal1 reporter activity from ROR / REV-ERB dependent transcriptional regulation. We suggest that weak coupling between core and secondary circadian feedback loops accounts for the observed behaviour of reindeer fibroblasts in vitro. Our findings highlight diversity in how the thermal environment affects the temporal organisation of mammals living under different thermoenergetic constraints.

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Appenroth, D., Ravuri, C. S., Torppa, S. K., Wood, S. H., Hazlerigg, D. G., West, A. C.. 2024-04-27. The reindeer circadian clock is rhythmic and temperature-compensated but shows evidence of weak coupling between the secondary and core molecular clock loops. https://doi.org/10.1101/2024.04.24.590752

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