Why are translationally sub-optimal synonymous codons used in Escherichia coli?

Natural selection favors certain synonymous codons which aid translation in Escherichia coli, yet codons not favored by translational selection persis t. We use the frequency distributions of synonymous polymorphisms to test t hree hypotheses for the existence of translationally sub-optimal codons: (1 ) selection is a relatively weak force, so there is a balance between mutat ion, selection, and drift; (2) at some sites there is no selection on codon usage, so some synonymous sites are unaffected by translational selection; and (3) translationally sub-optimal codons are favored by alternative sele ction pressures at certain synonymous sites. We find that when all the data is considered, model I is supported and both models 2 and 3 are rejected a s sole explanations for the existence of translationally sub-optimal codons . However, we find evidence in favor of both models 2 and 3 when the data i s partitioned between groups of amino acids and between regions of the gene s. Thus, all three mechanisms appear to contribute to the existence of tran slationally sub-optimal codons in E. coli.