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Updated: Feb 18, 2026

The Multifaceted Benefits of Protein Co-expression in Escherichia coli
Published on: February 5, 2015
Highly expressed genes evolve under strong epistasis from a proteome-wide scan in E. coli
Pouria Dasmeh1,2, Éric Girard1,2, Adrian W R Serohijos3,4
1Departement de Biochimie, Université de Montréal, 2900 Édouard-Montpetit, Montréal, Québec, H3T 1J4, Canada.
Abstract:
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.
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