GroEL dependency affects codon usage—support for a critical role of misfolding in gene evolution
Open Access
- 19 January 2010
- journal article
- Published by Springer Science and Business Media LLC in Molecular Systems Biology
- Vol. 6 (1), 340
- https://doi.org/10.1038/msb.2009.94
Abstract
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.Keywords
This publication has 60 references indexed in Scilit:
- Translationally Optimal Codons Associate with Structurally Sensitive Sites in ProteinsMolecular Biology and Evolution, 2009
- Fidelity at the Molecular Level: Lessons from Protein SynthesisCell, 2009
- An atlas of chaperone–protein interactions in Saccharomyces cerevisiae : implications to protein folding pathways in the cellMolecular Systems Biology, 2009
- Comprehensive mass-spectrometry-based proteome quantification of haploid versus diploid yeastNature, 2008
- Mistranslation-Induced Protein Misfolding as a Dominant Constraint on Coding-Sequence EvolutionCell, 2008
- The interaction network of the chaperonin CCTThe EMBO Journal, 2008
- Global aggregation of newly translated proteins in an Escherichia coli strain deficient of the chaperonin GroELProceedings of the National Academy of Sciences of the United States of America, 2006
- Pathways of chaperone-mediated protein folding in the cytosolNature Reviews Molecular Cell Biology, 2004
- Integrating high-throughput and computational data elucidates bacterial networksNature, 2004
- GroEL buffers against deleterious mutationsNature, 2002