The surprising negative correlation of gene length and optimal codon use - disentangling translational selection from GC-biased gene conversion in yeast

Yeast is a good organism to study this as equal numbers of optimal codons end in -GC and -AT and one may hence compare frequencies of optimal GC- with optimal AT-ending codons to disentangle the forces. Results of this study demonstrate in yeast frequencies of GC-ending (optimal AND non-optimal) codons decrease with gene length and increase with recombination. A decrease of GC-ending codons along genes contributes to the negative correlation with gene length. Correlations with recombination and gene expression differentiate between GC-ending and optimal codons, and also substitution patterns support effects of GC-biased gene conversion.While the general effect of GC-biased gene conversion is well known, the negative correlation of optimal codon use with gene length has not been considered in this context before. Initiation of gene conversion events in promoter regions and the presence of a gene conversion gradient most likely explain the observed decrease of GC-ending codons with gene length and gene position.Translational selection on synonymous codon use is indicated if frequencies of preferentially used, 'optimal', codons increase with expression level and correspond to the most abundant tRNA or to the tRNA with which they form the strongest binding - for several organisms, this seems to be the case (see for reviews [1-4]). Additional support for a beneficial role of certain 'optimal' codons in translation comes from laboratory studies [5-8]. Translational selection may act to maximise the speed of elongation, minimize the costs of proofreading or maximise the accuracy of translation [1], and depending on the selective target, one can test further distinct predictions. Under selection for translational accuracy we expect for example: (i) selection against translational errors to relate to the error's costs. As costs of an erroneous protein should accrue with each added amino acid during protein synthesis, one may expect long genes to experience higher optimal cod