Exonic Splicing Regulatory Elements Skew Synonymous Codon Usage near Intron-exon Boundaries in Mammals

Abstract

In mammals there is a bias in amino acid usage near splice sites that is explained, in large part, by the high density of exonic splicing enhancers (ESEs) in these regions. Is there a similar bias for the relative use of synonymous codons, and can any such bias be predicted by their abundance in ESEs? Prior reports suggested that such trends may exist. From analysis of human exons, we find that 47 of the 59 codons with at least one synonym show differential usage in the proximity of exon ends, of which 42 remain significant after correction for multiple testing. Within sets of synonymous codons those more preferred near splice sites are generally those that are relatively more abundant within the ESEs. However, the examples given previously appear exceptionally good fits and there exist many exceptions, the usage of lysine's codons being a case in point. Similar results are observed in mouse exons. We conclude that splice regulation impacts on the choice of synonymous codons in mammals, but the magnitude of this effect is less than might at first have been supposed.