Warren Spence, D. | bioRxiv Science

bioRxiv2025

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

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

genomics↗

bioRxiv2025

Studying sleep orthologs in Epsilonproteobacteria through an evolutionary lens: Investigating sleep mysteries through phylogenomics

The current study employed phylogenomic methods to examine the evolutionary role and significance of sleep-related genes in Sulfurimonas paralvinellae of the Epsilonproteobacteria class. This has facilitated the identification of conserved sleep orthologs, including DnaK, serine hydroxymethyltransferase, and potassium channel family proteins, exhibiting sequence similarities ranging from 39.13% to 61.45%. These findings align with prior research indicating that chaperones and ion channels are conserved during sleep. This was demonstrated by the observation that proteins with fewer domains exhibited more significant conservation than others, such as adenylate kinase, which is substantial under selective pressure. Distinct adaptations in bifunctional protein - serine/threonine kinases and phosphatases were linked to S. paralvinellae, an extremophilic organism adapted to high-pressure and/or high-temperature conditions, indicating functional divergence influenced by the organisms environment. The Gene Ontology study results indicated catalytic activity, potassium channel function, and cellular processes, underscoring the significance of ion channels in regulating the sleep-wake cycle. Furthermore, the categories not recognized as particularly significant for the over-represented genes encompassed metabolic and signal transduction categories, suggesting enhanced functional flexibility within this protein subfamily. The findings emphasize that orthologous interactions are complex and influenced by subfunctionalization and neofunctionalization of ecology and evolution. These findings enhance the existing understanding of the evolution of sleep-related genes and their association with metabolic and environmental changes, providing a foundation for subsequent experimental investigations and cross-taxonomic comparisons.

genomics↗