Mining conserved and divergent signals in 5’ splicing site sequences across fungi, metazoa and plants

The main steps of the splicing process are similar across eukaryotes. However differences in splicing factors, gene architecture and sequence divergences suggest clade-specific features of splicing and its regulation. In each organism the ensemble of 5’ splicing sequences reflects the balance between natural nucleotidic variability and minimal molecular constraints to assure splicing fidelity. This compromise shapes the underlying statistical patterns in donor sequences composition.

In this work we aimed to mine conserved and divergent signals in splicing donor sequences. As 5’ donor sequences are a major cue for proper recognition of splicing sites we reasoned that statistical regularities of their sequence composition might reflect biological functionality and evolutionary history associated to splicing mechanisms.

We considered a regularized maximum entropy modeling framework to mine for non-trivial two-site correlations in donor sequences of 30 different eukaryote organisms. Our approach allowed us to accommodate and extend within a unified framework many of the regularities observed in previous works, like the negative epistatic effects between exonic and intronic consensus sites. In addition, for each analyzed organism, we could identify minimal sets of two-site coupling patterns that could generate, at a given regularization level, observed one-site and two-site frequencies in donor sequences. Noticeably, performing a systematic and comparative analysis of 5’ss we showed that lineage information could be traced from joint di-nucleotide probabilities. Specifically, we could identify characteristic two-site coupling patterns for plants and for animals and argue that they could echo differences in splicing regulation previously reported between these groups.