CLOCK evolved in cnidaria to synchronize internal rhythms with diel environmental cues

Abstract

The circadian clock enables anticipation of the day/night cycle in animals ranging from cnidarians to mammals. Circadian rhythms are generated through a transcription-translation feedback loop (TTFL) involving negative and positive factors. CLOCK is a central conserved positive factor in the animal kingdom. However, the functional evolutionary origin and mechanism of action of CLOCK in basal animals are unknown. In cnidarians, the transcription of putative core clock genes, including Clock, is arrhythmic under constant conditions, and it is unclear how the TTFL model can regulate physiological rhythms. Here, we used the CRISPR/Cas9 system to generate a Clock mutant (Clock -/-) in Nematostella vectensis. High-throughput video tracking of locomotor activity in Clock -/- adults revealed that light regulates rhythmic behavior, while CLOCK maintains a 24-hour circadian rhythm under constant light conditions, and even under a 6-hour cycle, reminiscent of the tidal rhythm. Transcriptome profiling identified hundreds of differentially expressed genes in Clock -/- adults, particularly genes involved in cell cycle and neural development. In accordance with the rhythmic behavioral profile, computational analysis revealed rhythmic and arrhythmic gene expression in wild-type and Clock -/- adults, respectively, under constant dark conditions. Notably, hierarchal light-and Clock-signaling is required to drive rhythmic transcription of the core clock genes. These findings demonstrate that CLOCK has evolved in cnidarians to maintain synchronized 24-hour rhythmic physiology and behavior despite the chaotic inputs of environmental cues.

Cnidarians are CLOCKing in

“…Was it before or after the divergence of bilaterians and a related phylum known as the cnidarians? Now, in eLife, Raphael Aguillon, Mieka Rinsky, Oren Levy and colleagues at Bar-Ilan University report the results of experiments on Nematostella vectensis – a cnidarian known as the starlet sea anemone – that shed light on this critical question ( Aguillon et al, 2023 ).…”