Chaperonin activity modulates codon adaptation

Abstract

Mol Syst Biol. 6: 6 Since the discovery of the genetic code by Holley, Khorana, and Nirenberg, researchers have been fascinated by the apparent redundancy of synonymous codons that code for the same amino acid. Subsequent work led to the discovery that synonymous codons are not used randomly in coding sequences. Rather, classes of genes that are characterized by a specific codon usage bias can be identified. Thus, ‘optimal codons’ were defined as codons that are enriched in highly expressed genes. Based on this notion, bioinformatics researchers have developed the Codon Adaptation Index, which has been adopted as an approximate measure for overall gene expression level. The classical theory of codon bias posits that optimal codons correlate with the abundances of cognate tRNAs, and thereby increase translational efficiency and accuracy (Ikemura, 1981) by reducing the rate of ribosomal stalling and decreasing the chances of incorporating the wrong amino acid. Consequently, optimal codons are thought to prevent mistranslation‐induced misfolding (Drummond and Wilke, 2008). In a recent study published in Molecular Systems Biology , Warnecke and Hurst (2010) report evidence for a novel mechanism underlying optimal codon usage. They hypothesize a novel link between codon bias and the cellular folding machinery; namely, the GroEL chaperonin complex. Specifically, proteins that only sporadically rely on chaperones (in trans ) to prevent misfolding are …