Warnecke, T. and Hurst, L. D., 2010. GroEL dependency affects codon usage-support for a critical role of misfolding in gene evolution. Molecular Systems Biology, 6, 340.
It has recently been suggested that the use of optimal codons limits mistranslation-induced protein misfolding, yet evidence for this remains largely circumstantial. In contrast, molecular chaperones have long been recognized to play crucial roles in misfolding prevention and remedy. We propose that putative error limitation in cis can be elucidated by examining the interaction between codon usage and chaperoning processes. Using Escherichia coli as a model system, we find that codon optimality covaries with dependency on the chaperonin GroEL. Sporadic but not obligate substrates of GroEL exhibit higher average codon adaptation and are conspicuously enriched for optimal codons at structurally sensitive sites. Further, codon optimality of sporadic clients is more conserved in the E. coli clone Shigella dysenteriae. We suggest that highly expressed genes cannot routinely use GroEL for error control so that codon usage has evolved to provide complementary error limitation. These findings provide independent evidence for a role of misfolding in shaping gene evolution and highlight the need to co-characterize adaptations in cis and trans to unravel the workings of integrated molecular systems. Molecular Systems Biology 6: 340; published online 19 January 2010; doi:10.1038/msb.2009.94
|Item Type ||Articles|
|Creators||Warnecke, T.and Hurst, L. D.|
|Departments||Faculty of Science > Biology & Biochemistry|
|Publisher Statement||msb200994.pdf: © Warnecke and Hurst 2010. Molecular Systems Biology 6 Article number: 340 doi:10.1038/msb.2009.94 This is an open-access article distributed under the terms of the Creative Commons Attribution Licence, which permits distribution and reproduction in any medium, provided the original author and source are credited. Creation of derivative works is permitted but the resulting work may be distributed only under the same or similar licence to this one. This licence does not permit commercial exploitation without specific permission.|
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