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MBE Advance Access published online on November 13, 2006

Molecular Biology and Evolution, doi:10.1093/molbev/msl166
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© The Author 2006. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org
Accepted November 2, 2006

Research Article

Synonymous Codon Usage in Escherichia coli - Selection for Translational Accuracy

Nina Stoletzki 1 * and Adam Eyre-Walker 2

1 Ludwig-Maximilan Universität, Biocenter, Grosshaderner Str. 2, D-82152 Planegg-Martinsried; Center for Study of Evolution, School of Life Sciences, University of Sussex, Brighton BN1 9QG, UK
2 Center for Study of Evolution, School of Life Sciences, University of Sussex, Brighton BN1 9QG, UK; National Evolutionary Synthesis Center, Durham NC 27707, USA

* To whom correspondence should be addressed.
Nina Stoletzki, E-mail: nstoletzki{at}googlemail.com


   Abstract

In many organisms, selection acts on synonymous codons to improve translation. However the precise basis of this selection remains unclear in the majority of species. Selection could be acting to maximise the speed of elongation, to minimise the costs of proofreading or to maximise the accuracy of translation. Using several datasets, we find evidence that codon use in Escherichia coli is biased to reduce the costs of both mis-sense and non-sense translational errors. Highly conserved sites and genes have higher codon bias than less conserved ones, and codon bias is positively correlated to gene length and production costs, both indicating selection against mis-sense errors. Additionally, codon bias increases along the length of genes, indicating selection against non-sense errors. Doublet mutations or replacement substitutions do not explain our observations. The correlations remain when we control for expression level, and for conflicting selection pressures at the start and end of genes. Considering each amino acid by itself confirms our results. We conclude that selection on synonymous codon use in E. coli is largely due to selection for translational accuracy, to reduce the costs of both mis-sense and of non-sense errors.


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