Examining Sleep Signals at the Cradle of Life: Can phylogenomic analysis of the Last Universal Common Ancestor (LUCA) reveal the fundamental role of sleep?

Pandi-Perumal, S. R.; Saravanan, K. M.; Warren Spence, D.; Paul, S.; Namasivayam, G. P.; Chidambaram, S. B.

doi:10.1101/2025.03.21.644522

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bioRxiv · 10.1101/2025.03.21.644522

Examining Sleep Signals at the Cradle of Life: Can phylogenomic analysis of the Last Universal Common Ancestor (LUCA) reveal the fundamental role of sleep?

Pandi-Perumal, S. R.·Saravanan, K. M.·Warren Spence, D.·Paul, S.·Namasivayam, G. P.·Chidambaram, S. B.

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Abstract

In common with most physiological activities, sleep is a highly evolutionarily conserved function. Nevertheless, the purpose of sleep remains inadequately investigated. One possible cause of this deficiency is the limitations of the traditional methods used for examining sleep. Up to this time, the mainstay tool used to look at the evolutionary basis of sleep has been phylogenetic analysis. This approach has provided many valuable insights into sleep, yet it has left many questions unanswered. The present study uses a relatively new hybrid technique at the interface of phylogenetics and genomics, known as phylogenomic analysis. This study is the first to use phylogenomic analysis to investigate the basis of sleep by evaluating the presence and conservation of sleep-related genes in the reconstructed genome of the Last Universal Common Ancestor (LUCA). Our gene set enrichment analysis of humans and LUCA indicates that the conserved sleep genes are linked to signaling, metabolism, and circadian rhythm pathways, suggesting that these genes possess primordial roles in essential physiological functions. These findings indicate that the component genes carry out essential physiological tasks that were subsequently repurposed to regulate sleep in more advanced organisms throughout evolution. This study lays the foundation for a systematic phylogenomic exploration of sleep-related genes, connecting molecular evolution with sleep science. By tracing the biological history of sleep to its deep evolutionary origins, our research presents novel insights into sleeps nature, origin, and evolutionary function, paving the way for further interdisciplinary exploration of the biology of sleep. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=122 SRC="FIGDIR/small/644522v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@17adc89org.highwire.dtl.DTLVardef@124de86org.highwire.dtl.DTLVardef@18d3e5corg.highwire.dtl.DTLVardef@1f93b06_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Pandi-Perumal, S. R., Saravanan, K. M., Warren Spence, D., Paul, S., Namasivayam, G. P., Chidambaram, S. B.. 2025-03-23. Examining Sleep Signals at the Cradle of Life: Can phylogenomic analysis of the Last Universal Common Ancestor (LUCA) reveal the fundamental role of sleep?. https://doi.org/10.1101/2025.03.21.644522

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