title: Evidence for a trade-off between translational efficiency and splicing regulation in determining synonymous codon usage in Drosophila melanogaster.
abstract: In Drosophila melanogaster, synonymous codons corresponding to the most abundant cognate tRNAs are used more frequently, especially in highly expressed genes. Increased use of such "optimal" codons is considered an adaptation for translational efficiency. Need it always be the case that selection should favor the use of a translationally optimal codon? Here, we investigate one possible confounding factor, namely, the need to specify information in exons necessary to enable correct splicing. As expected from such a model, in Drosophila many codons show different usage near intron-exon boundaries versus exon core regions. However, this finding is in principle also consistent with Hill-Robertson effects modulating usage of translationally optimal codons. However, several results support the splice model over the translational selection model: 1) the trends in codon usage are strikingly similar to those in mammals in which codon usage near boundaries correlates with abundance in exonic splice enhancers (ESEs), 2) codons preferred near boundaries tend to be enriched for A and avoid C (conversely those avoided near boundaries prefer C rather than A), as expected were ESEs involved, and 3) codons preferred near boundaries are typically not translationally optimal. We conclude that usage of translationally optimal codons usage is compromised in the vicinity of splice junctions in intron-containing genes, to the effect that we observe higher levels of usage of translationally optimal codons at the center of exons. On the gene level, however, controlling for known correlates of codon bias, the impact on codon usage patterns is quantitatively small. These results have implications for inferring aspects of the mechanism of splicing given nothing more than a well-annotated genome.
authors: Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, United Kingdom.
authors: Tobias
authors: T
authors: Warnecke
authors: Laurence D
authors: LD
authors: Hurst
mesh_terms: D000818:Animals; D001483:Base Sequence; D003062:Codon / Q000235:genetics*; D017124:Conserved Sequence; D004331:Drosophila melanogaster / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D005091:Exons / Q000235:genetics; D017344:Genes, Insect; D007438:Introns / Q000235:genetics; D009711:Nucleotides; D016366:Open Reading Frames / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D012044:Regression Analysis; D012641:Selection, Genetic
chemical_list: D003062:Codon; D009711:Nucleotides