Rocha Eduardo P C, Danchin Antoine
Unité GGB, Institut Pasteur, Paris, France.
Mol Biol Evol. 2004 Jan;21(1):108-16. doi: 10.1093/molbev/msh004. Epub 2003 Oct 31.
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.
蛋白质中氨基酸替换率的变化取决于几个变量。其中，蛋白质的表达水平、功能类别、必需性或其氨基酸残基的代谢成本可能起重要作用。然而，在比较分析中尚未评估每个变量的相对重要性。为此，我们结合了两种有充分文献记载的模式细菌——大肠杆菌和枯草芽孢杆菌——中有关这些变量和进化速率的现有数据进行回归分析。在这两种细菌中，蛋白质在细胞中的表达水平是迄今为止限制氨基酸替换率的最重要驱动力。随后将其他变量纳入分析几乎没有增加更多信息。此外，当在大肠杆菌数据的分析中纳入同义替换率时，只有表达水平这一变量仍具有统计学意义。非同义替换率被证明与表达水平相关，且独立于同义替换率。这些结果表明表达水平，或至少翻译优化的密码子使用偏好，对细菌中的非同义替换率有重要的直接影响。它们还表明，当纳入对该变量的控制时，必需性在细菌蛋白质进化速率中不起显著作用，这与真核生物的情况相同。
