ArticlePLoS genetics2025
Evolution of canonical circadian clock genes underlies unique sleep strategies of marine mammals for secondary aquatic adaptation.
Article in PLoS genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- From few to many: How non-model organisms' genomics broadened our understanding of molecular evolution.Genetics and molecular biology · 2026Article
- Molecular Evolution of the NLR Gene Family Reveals Diverse Innate Immune Strategies in Bats.Biomolecules · 2025Article
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9 authors.
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Abstract
To satisfy the needs of sleeping underwater, marine mammals, including cetaceans, sirenians, and pinnipeds, have evolved an unusual form of sleep, known as unihemispheric slow-wave sleep (USWS), in which one brain hemisphere is asleep while the other is awake. All aquatic cetaceans have only evolved USWS without rapid eye movement (REM) sleep, whereas aquatic sirenians and amphibious pinnipeds display both bihemispheric slow-wave sleep (BSWS) and USWS, as well as REM sleep. However, the molecular genetic changes underlying USWS remain unknown. The present study investigated the evolution of eight canonical circadian genes and found that positive selection occurred mainly within cetacean lineages. Furthermore, convergent evolution was observed in lineages with USWS at three circadian clock genes. Remarkably, in vitro assays showed that cetacean-specific mutations increased the nuclear localization of zebrafish clocka, and enhanced the transcriptional activation activity of Clocka and Bmal1a. In vivo, transcriptome analysis showed that the overexpression of the cetacean-specific mutant clocka (clocka-mut) caused the upregulation of the wakefulness-promoting glutamatergic genes and the differential expression of multiple genes associated with sleep regulation. In contrast, the GABAergic and cholinergic pathways, which play important roles in promoting sleep, were downregulated in the bmal1a-mut-overexpressing zebrafish. Concordantly, sleep time of zebrafish overexpressing clocka-mut and bmal1a-mut were significantly less than the zebrafish overexpressing the wild-type genes, respectively. These findings support our hypothesis that canonical circadian clock genes may have evolved adaptively to enhance circadian regulation ability relating to sleep in cetaceans and, in turn, contribute to the formation of USWS.
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