Department of Genetics, Yale University, New Haven, Connecticut, USA.
Genome Biol Evol. 2011;3:456-75. doi: 10.1093/gbe/evr046. Epub 2011 May 21.
Theory suggests that biological modularity and robustness allow for maintenance of fitness under mutational change, and when this change is adaptive, for evolvability. Empirical demonstrations that these traits promote evolvability in nature remain scant however. This is in part because modularity, robustness, and evolvability are difficult to define and measure in real biological systems. Here, we address whether structural modularity and/or robustness confer evolvability at the level of proteins by looking for associations between indices of protein structural modularity, structural robustness, and evolvability. We propose a novel index for protein structural modularity: the number of regular secondary structure elements (helices and strands) divided by the number of residues in the structure. We index protein evolvability as the proportion of sites with evidence of being under positive selection multiplied by the average rate of adaptive evolution at these sites, and we measure this as an average over a phylogeny of 25 mammalian species. We use contact density as an index of protein designability, and thus, structural robustness. We find that protein evolvability is positively associated with structural modularity as well as structural robustness and that the effect of structural modularity on evolvability is independent of the structural robustness index. We interpret these associations to be the result of reduced constraints on amino acid substitutions in highly modular and robust protein structures, which results in faster adaptation through natural selection.
理论表明，生物的模块化和稳健性允许在突变变化下维持适应性，并且当这种变化是适应性的时，允许进化。然而，实证证明这些特征在自然界中促进了进化性仍然很少。部分原因是因为模块化、稳健性和进化性在真实的生物系统中很难定义和衡量。在这里，我们通过寻找蛋白质结构模块化、结构稳健性和进化性指标之间的关联，来研究结构模块化和/或稳健性是否在蛋白质水平上赋予了进化性。我们提出了一种新的蛋白质结构模块化指数：规则二级结构元素（螺旋和链）的数量除以结构中的残基数。我们将蛋白质进化性指数定义为具有正选择证据的位点比例乘以这些位点的平均适应性进化速度，并将其作为 25 种哺乳动物种系发生的平均值来衡量。我们使用接触密度作为蛋白质可设计性的指标，也就是结构稳健性的指标。我们发现蛋白质进化性与结构模块化和结构稳健性呈正相关，并且结构模块化对进化性的影响独立于结构稳健性指数。我们将这些关联解释为高度模块化和稳健的蛋白质结构中氨基酸替换的约束减少的结果，这导致通过自然选择更快地适应。
