bioRxiv Science⌕ Search
Home/Archive/bioRxiv

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.
View original source ↗Export metadata ↓

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

Source connections

Explore related subjects

genomicsPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

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

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Structural variation in repeat elements is widespread in normal human tissues and in tumorigenesis

Somatic mosaicism contributes to genomic variation, yet postzygotic structural variants remain under-characterized. We performed long- and short-read WGS from multiple individuals (n=47 normal tissues; n=168 samples) and identified mosaic structural variants in all individuals and germ layers, impacting a median 285.2 kb/genome. Nearly half of breakpoints were independently validated, with tissue distributions reflecting both early and late developmental origins. Most mosaic variants were repeat-mediated and 8.3% overlapped functional elements, an enrichment compared to germline variants. To extend these analyses in samples where long-read sequencing is infeasible, we measured repeat alterations from short-read sequencing, recapitulating mosaic tissue-specific differences. We characterized tumor- and tissue- specific variation in repeats across 15 cancer types and found tumor-related repeat variation to be similar in scale to that of normal mosaic variation. Tracking repeat changes in cell-free DNA provided a noninvasive approach for tumor monitoring. Our analyses revealed widespread repeat-driven structural variation in health and disease.

genomics↗
bioRxiv2026

RNA isoform-resolved multiplexed sequencing with bioorthogonal barcoding

RNA isoform dysregulation drives disease pathogenesis and is the target of FDA-approved splice-switching therapeutics. However, multiplexed sequencing methods discard splice junction information because only 3' termini are barcoded and counted. Here, we repurpose acylation and click chemistries to conjugate bioorthogonal barcodes (bobcodes) directly onto multiple internal positions along cellular RNAs. Bobcoded RNAs from multiple samples are pooled for multiplexed cDNA synthesis, during which reverse transcriptase switches from each RNA template onto its tethered bobcode with greater than 99% accuracy in species mixing experiments. Bobcode attachment intervals set cDNA insert sizes without a library fragmentation step, and priming with poly(dT) or random hexamers selects between 3'-end counting and full-length isoform capture. A bioorthogonal barcode-sequencing (BOB-seq v0.1) drug screen identifies transcriptome-wide on- and off-target RNA splicing effects and outperforms existing multiplexing RNA sequencing methods in workflow simplicity, sample-to-sample variability, and barcoding accuracy. Bobcodes add isoform resolution to scalable multiplexed RNA sequencing.

genomics↗
bioRxiv2026

Structural polymorphism and population-variable coding capacity of HERV-K(HML-2) in human pangenomes

Approximately 8% of the human genome is derived from ancient retroviral infections. The most recently integrated of these endogenous retroviruses is the HERV-K(HML-2) clade, whose expression has been associated with cancer, amyotrophic lateral sclerosis, and embryogenesis. Studies of HERV expression, particularly HML-2, have relied predominantly on short-read sequencing. However, the high similarity among HML-2 proviruses prevents many short reads from being assigned uniquely to individual loci. We therefore compared haplotype-resolved long-read genome assemblies from 292 donors to resolve variation in proviral structure and coding capacity. Several loci previously thought to be fixed were structurally polymorphic. Tandem arrays occurred at 13 loci and contained up to six proviral copies in a single array. At 8q11.23, we identified a previously undescribed full-length provirus in one haplotype. All 583 other haplotypes carried a solo-LTR. We found that standard reference genomes failed to represent the coding capacity retained in many individuals, whose proviruses contained intact open reading frames despite disruptive mutations in the reference sequences. Short-read genotypes left 32.5% of the tested donor-variant pairs unresolved at sites associated with viral reading frames. These findings show why HML-2 expression must be interpreted in the context of the structural and coding alleles each individual carries.

genomics↗