Finding exonic islands in a sea of non-coding sequence: splicing related constraints on protein composition and evolution are common in intron-rich genomes

Tobias Warnecke , Joanna L Parmley and Laurence D Hurst

Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK

author email corresponding author email

Genome Biology 2008, 9:R29doi:10.1186/gb-2008-9-2-r29


Published:	7 February 2008

Subject areas: Evolution, Molecular biology, Bioinformatics

Abstract

Background

In mammals, splice-regulatory domains impose marked trends on the relative abundance of certain amino acids near exon-intron boundaries. Is this a mammalian particularity or symptomatic of exonic splicing regulation across taxa? Are such trends more common in species that a priori have a harder time identifying exon ends, that is, those with pre-mRNA rich in intronic sequence? We address these questions surveying exon composition in a sample of phylogenetically diverse genomes.

Results

Biased amino acid usage near exon-intron boundaries is common throughout the metazoa but not restricted to the metazoa. There is extensive cross-species concordance as to which amino acids are affected, and reduced/elevated abundances are well predicted by knowledge of splice enhancers. Species expected to rely on exon definition for splicing, that is, those with a higher ratio of intronic to coding sequence, more introns per gene and longer introns, exhibit more amino acid skews. Notably, this includes the intron-rich basidiomycete Cryptococcus neoformans, which, unlike intron-poor ascomycetes (Schizosaccharomyces pombe, Saccharomyces cerevisiae), exhibits compositional biases reminiscent of the metazoa. Strikingly, 5 prime ends of nematode exons deviate radically from normality: amino acids strongly preferred near boundaries are strongly avoided in other species, and vice versa. This we suggest is a measure to avoid attracting trans-splicing machinery.

Conclusion

Constraints on amino acid composition near exon-intron boundaries are phylogenetically widespread and characteristic of species where exon localization should be problematic. That compositional biases accord with sequence preferences of splice-regulatory proteins and are absent in ascomycetes is consistent with selection on exonic splicing regulation.