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Mol. Biol. Evol. 21(1):108-116. 2004
DOI: 10.1093/molbev/msh004
© 2004 by the Society for Molecular Biology and Evolution. ISSN: 0737-4038

An Analysis of Determinants of Amino Acids Substitution Rates in Bacterial Proteins

Eduardo P. C. Rocha*,{dagger} and Antoine Danchin*,{ddagger}

* Unité GGB, Institut Pasteur, Paris, France
{dagger} Atelier de BioInformatique, Université Pierre et Marie Curie, Paris, France
{ddagger} HKU-Pasteur Research Centre, Hong Kong

E-mail: erocha{at}abi.snv.jussieu.fr.

The variation of amino acid substitution rates in proteins depends on several variables. Among these, the protein's expression level, functional category, essentiality, or metabolic costs of its amino acid residues may play an important role. However, the relative importance of each variable has not yet been evaluated in comparative analyses. To this aim, we made regression analyses combining data available on these variables and on evolutionary rates, in two well-documented model bacteria, Escherichia coli and Bacillus subtilis. In both bacteria, the level of expression of the protein in the cell was by far the most important driving force constraining the amino acids substitution rate. Subsequent inclusion in the analysis of the other variables added little further information. Furthermore, when the rates of synonymous substitutions were included in the analysis of the E. coli data, only the variable expression levels remained statistically significant. The rate of nonsynonymous substitution was shown to correlate with expression levels independently of the rate of synonymous substitution. These results suggest an important direct influence of expression levels, or at least codon usage bias for translation optimization, on the rates of nonsynonymous substitutions in bacteria. They also indicate that when a control for this variable is included, essentiality plays no significant role in the rate of protein evolution in bacteria, as is the case in eukaryotes.

Key Words: protein evolution • substitution rates • eukaryotes • essentiality • expression levels • functional categories


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