Conserved and divergent signals in 5' splice site sequences across fungi, metazoa and plants

PLoS Comput Biol. 2023 Oct 13;19(10):e1011540. doi: 10.1371/journal.pcbi.1011540. eCollection 2023 Oct.

Abstract

In eukaryotic organisms the ensemble of 5' splice site sequences reflects the balance between natural nucleotide variability and minimal molecular constraints necessary to ensure splicing fidelity. This compromise shapes the underlying statistical patterns in the composition of donor splice site sequences. The scope of this study was to mine conserved and divergent signals in the composition of 5' splice site sequences. Because 5' donor sequences are a major cue for proper recognition of splice sites, we reasoned that statistical regularities in their composition could reflect the biological functionality and evolutionary history associated with splicing mechanisms. Results: We considered a regularized maximum entropy modeling framework to mine for non-trivial two-site correlations in donor sequence datasets corresponding to 30 different eukaryotes. For each analyzed species, we identified minimal sets of two-site coupling patterns that were able to replicate, at a given regularization level, the observed one-site and two-site frequencies in donor sequences. By performing a systematic and comparative analysis of 5'splice sites we showed that lineage information could be traced from joint di-nucleotide probabilities. We were able to identify characteristic two-site coupling patterns for plants and animals, and propose that they may echo differences in splicing regulation previously reported between these groups.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Eukaryota
  • Fungi / genetics
  • Introns
  • Nucleotides
  • Plants / genetics
  • RNA Splice Sites* / genetics
  • RNA Splicing* / genetics

Substances

  • RNA Splice Sites
  • Nucleotides

Grants and funding

MY ackowledges support from Fondo para la Investigación Científica y Tecnológica (ANPCyT-FONCYT, grant PICT-2015-3147). AC acknowledges support from Secretaría de Ciencia y Técnica, Universidad de Buenos Aires (grant 20020170100356BA). AC and MY are members of Carrera de Investigador of Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.