Biology subjects

Creasey, L. D.

Publications and source records attributed to Creasey, L. D..

2 recordsLinked to original sources

bioRxiv2026

Synonymous codon usage is biased for and against m⁶A RRACH motifs in mammals

RNA methylation at N6-adenosine (m6A) predominantly occurs within RRACH motifs, yet the forces shaping these motifs in coding regions remain unclear. Here we show that the synonymous codon combinations able to form or disrupt RRACH sites are used non-randomly across mammals. Using 13,491 protein-coding genes from 261 species, we identified genes significantly enriched or depleted in RRACH motifs, a pattern consistent with gene-specific selection for or against m6A potential. Genes enriched in RRACH sites were linked to ubiquitin-like conjugation and cell cycle regulation, whereas transmembrane and HOX genes were RRACH-poor, likely reflecting sequence incompatibility with CpG dinucleotides. Cross-species comparison with Caenorhabditis elegans, which lacks mRNA m6A methylation, revealed reciprocal RRACH frequencies, as expected if these motifs are under selection in m6A-competent genomes but evolve without this constraint otherwise. At the codon level, specific amino acid pairs, particularly threonine-ending dyads, were biased toward RRACH-forming codons while others were depleted, indicating that synonymous codon choice is skewed for and against motif formation. RRACH motifs were also non-randomly distributed along coding sequences, depleted near start codons and enriched toward the 3' end, consistent with known m6A profiles. Finally, analysis of cancer mutations revealed tissue-specific gain and loss of RRACH sites, reflecting context-dependent remodeling of methylation potential. Together, these results show that synonymous codon usage is systematically biased for and against m6A RRACH motifs, pointing to an evolutionary coupling between the genetic code and the epitranscriptomic landscape.

genomics↗

bioRxiv2025

The Evolutionary Flexibility of the Drosophila Circadian Clock: Network Constraints or Adaptive Freedom?

The study of network evolution is critical to understanding how complex biological processes arise and adapt over time. Protein networks, composed of interacting components, can exhibit varying degrees of conservation and flexibility, enabling organisms to fine-tune their responses to environmental changes. Using the circadian clock system in Drosophila as a case study, we explore how such networks evolve. We leverage the recently published 101 Drosophilidae genome project to analyze the evolution and co-evolution of 11 core clock proteins across 65 species spanning about 60 million years of evolution. A sliding window analysis of coding regions reveals substantial heterogeneity in nucleotide divergence, with Clk and per exhibiting high divergence, whereas Pdp1 and sgg show virtually no evolutionary change. Additionally, we assessed interdependent amino acid evolution across different proteins, identifying 67 co-evolving site pairs, primarily between CLK-PER, CLK-CWO, and SGG-PER. Using codon-based models of evolution we found four genes (cwo, jet, per, and sgg) showing evidence of positive selection. Since several clock proteins are pleiotropic, we tested whether their multifunctionality influences their evolutionary constraints. Using alternative approaches to assess pleiotropy, we found no significant correlation between pleiotropy and the non-synonymous substitution rate (Ka) in 440 Drosophila proteins, including circadian clock ones. Overall, our findings suggest that the circadian clock network does not impose strong constraints on the evolution of its components. This flexibility may facilitate species-specific adaptation of the clock and allow the pleiotropic functions of clock proteins.

evolutionary biology↗