Ensemble epistasis: thermodynamic origins of nonadditivity between mutations.

ABSTRACT: Epistasis-when mutations combine nonadditively-is a profoundly important aspect of biology. It is often difficult to understand its mechanistic origins. Here, we show that epistasis can arise from the thermodynamic ensemble, or the set of interchanging conformations a protein adopts. Ensemble epistasis occurs because mutations can have different effects on different conformations of the same protein, leading to nonadditive effects on its average, observable properties. Using a simple analytical model, we found that ensemble epistasis arises when two conditions are met: (1) a protein populates at least three conformations and (2) mutations have differential effects on at least two conformations. To explore the relative magnitude of ensemble epistasis, we performed a virtual deep-mutational

SUBMITTER: Morrison AJ 

PROVIDER: S-EPMC8633102 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature