title: Purifying Selection on Exonic Splice Enhancers in Intronless Genes.
abstract: Exonic splice enhancers (ESEs) are short nucleotide motifs, enriched near exon ends, that enhance the recognition of the splice site and thus promote splicing. Are intronless genes under selection to avoid these motifs so as not to attract the splicing machinery to an mRNA that should not be spliced, thereby preventing the production of an aberrant transcript? Consistent with this possibility, we find that ESEs in putative recent retrocopies are at a higher density and evolving faster than those in other intronless genes, suggesting that they are being lost. Moreover, intronless genes are less dense in putative ESEs than intron-containing ones. However, this latter difference is likely due to the skewed base composition of intronless sequences, a skew that is in line with the general GC richness of few exon genes. Indeed, after controlling for such biases, we find that both intronless and intron-containing genes are denser in ESEs than expected by chance. Importantly, nucleotide-controlled analysis of evolutionary rates at synonymous sites in ESEs indicates that the ESEs in intronless genes are under purifying selection in both human and mouse. We conclude that on the loss of introns, some but not all, ESE motifs are lost, the remainder having functions beyond a role in splice promotion. These results have implications for the design of intronless transgenes and for understanding the causes of selection on synonymous sites.
authors.affiliation: Department of Biology and Biochemistry, The Milner Centre for Evolution, University of Bath, Bath, United Kingdom r.savisaar@bath.ac.uk.
authors.forename: Rosina
authors.initials: R
authors.lastname: Savisaar
authors.affiliation: Department of Biology and Biochemistry, The Milner Centre for Evolution, University of Bath, Bath, United Kingdom.
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Hurst
mesh_terms: D000818:Animals; D019295:Computational Biology / Q000379:methods; D004742:Enhancer Elements, Genetic; D019143:Evolution, Molecular; D005091:Exons; D006801:Humans; D007438:Introns; D051379:Mice; D009154:Mutation; D059645:Mutation Rate; D059372:Nucleotide Motifs; D020641:Polymorphism, Single Nucleotide; D022821:RNA Splice Sites; D012326:RNA Splicing; D012641:Selection, Genetic / Q000235:genetics / Q000276:immunology
chemical_list: D022821:RNA Splice Sites
keywords: SR proteins; avoidance selection; exonic splice enhancers; intronless genes; splice control