Codon choice and gene expression: synonymous codons differ in translational accuracy.

Abstract

Ribosomes programmed by different synonymous codons also differ in discriminating among near-cognate aminoacylated tRNAs. In the initial step of the recognition reaction ribosomes programmed by UUC discriminate less well than ribosomes programmed by UUU against ternary complexes containing three types of Leu-tRNA, and ribosomes programmed by CUC discriminate less well than ribosomes programmed by CUU against ternary complexes containing Phe-tRNA. Furthermore, in the proofreading step ribosomes programmed by UUC discriminate less well than ribosomes programmed by UUU against two of three near-cognate LeutRNAs, and ribosomes programmed by CUC discriminate less well than ribosomes programmed by CUU against nearcognate Phe-tRNA. The codon-induced change in reaction rate with near-cognate ternary complexes is greater than that with cognate ternary complexes: the most efficient codon is, therefore, the least accurate. Because the efficient, but inaccurate, codon UUC is used preferentially in highly expressed mRNAs of Escherichia coli, maxinmization of translational accuracy apparently has not been significant in the evolution of this particular biased codon choice in E. coli.The ribosomes, tRNAs, and factors of the translational apparatus are usually thought devoid of intrinsic specificity because any specificity could interfere with accurate reading of mRNA. But surprisingly the translational apparatus shows a distinct specificity for certain codon-tRNA pairs. The translational apparatus of many organisms appears to prefer a distinct subset of possible codons in highly expressed genes (1-4). Explanations for this bias based on the existence of preferred structures for mRNAs are unconvincing, and attempts to explain the bias now focuses on the hypothesis that the disfavored codons are either less rapidly or less accurately read by the translational apparatus. Evidence for the idea that disfavored codons are translated less rapidly includes the finding that the average in vivo translational-step times of highly expressed mRNAs increase when the mRNAs contain these codons (5) and that pause sites in translating several mRNAs associate with the disfavored codons (6). These findings have often been attributed to the fact that disfavored codons are generally translated by low-abundance tRNAs (7). However, we recently presented evidence that the ribosome works faster with certain codontRNA pairs (8). Thus, we showed in vitro that the phenylalanine codon UUC is more rapidly translated by Phe-tRNA than is the synonymous codon UUU. Results pointing to the same conclusion have been obtained in vivo by Curran and Yarus (29). That a favored codon is translated almost twice as fast as its disfavored synonym supports the idea that need for translational efficiency is one factor driving the evolution of codon bias in Escherichia coli.Another factor possibly contributing to the evolution of codon bias is the need for accurate translation. The choice of asparagine codons may provide an example of this effect. Parker and his co...

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