title: Finding exonic islands in a sea of non-coding sequence: splicing related constraints on protein composition and evolution are common in intron-rich genomes.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK. tw233@bath.ac.uk
authors.forename: Tobias
authors.initials: T
authors.lastname: Warnecke
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Parmley
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Hurst
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics*; D000818:Animals; D019143:Evolution, Molecular; D005091:Exons; D016678:Genome; D006801:Humans; D007438:Introns; D051379:Mice; D010802:Phylogeny; D017434:Protein Structure, Tertiary / Q000235:genetics*; D012326:RNA Splicing; D020506:Untranslated Regions / Q000235:genetics*
chemical_list: D020506:Untranslated Regions