Departement de Biochimie, Université de Montréal, 2900 Édouard-Montpetit, Montréal, Québec, H3T 1J4, Canada.
Centre Robert Cedergren en Bioinformatique et Génomique, Université de Montréal, 2900 Édouard-Montpetit, Montréal, Québec, H3T 1J4, Canada.
Sci Rep. 2017 Nov 20;7(1):15844. doi: 10.1038/s41598-017-16030-z.
Epistasis or the non-additivity of mutational effects is a major force in protein evolution, but it has not been systematically quantified at the level of a proteome. Here, we estimated the extent of epistasis for 2,382 genes in E. coli using several hundreds of orthologs for each gene within the class Gammaproteobacteria. We found that the average epistasis is ~41% across genes in the proteome and that epistasis is stronger among highly expressed genes. This trend is quantitatively explained by the prevailing model of sequence evolution based on minimizing the fitness cost of protein unfolding and aggregation. The genes with the highest epistasis are also functionally involved in the maintenance of proteostasis, translation and central metabolism. In contrast, genes evolving with low epistasis mainly encode for membrane proteins and are involved in transport activity. Our results highlight the coupling between selection and epistasis in the long-term evolution of a proteome.
上位性或突变效应的非加性是蛋白质进化的主要力量，但它在蛋白质组水平上尚未得到系统地量化。在这里，我们使用了 gammaproteobacteria 类中的每个基因的数百个直系同源物，来估计大肠杆菌 2382 个基因的上位性程度。我们发现，在蛋白质组中，平均上位性约为 41%，而且在上调基因中更为强烈。这种趋势可以通过基于最小化蛋白质展开和聚集的适应性成本的序列进化的流行模型来定量解释。具有最高上位性的基因也在蛋白质稳态、翻译和中心代谢的维持中具有功能相关性。相比之下，具有低上位性的基因主要编码膜蛋白，并参与运输活动。我们的结果强调了选择和上位性在蛋白质组长期进化中的耦合。
