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How mutational epistasis impairs predictability in protein evolution and design.


ABSTRACT: There has been much debate about the extent to which mutational epistasis, that is, the dependence of the outcome of a mutation on the genetic background, constrains evolutionary trajectories. The degree of unpredictability introduced by epistasis, due to the non-additivity of functional effects, strongly hinders the strategies developed in protein design and engineering. While many studies have addressed this issue through systematic characterization of evolutionary trajectories within individual enzymes, the field lacks a consensus view on this matter. In this work, we performed a comprehensive analysis of epistasis by analyzing the mutational effects from nine adaptive trajectories toward new enzymatic functions. We quantified epistasis by comparing the effect of mutations occurring bet

SUBMITTER: Miton CM 

PROVIDER: S-EPMC4918425 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature