Epistasis in a Fitness Landscape Defined by Antibody-Antigen Binding Free Energy.

ABSTRACT: Epistasis is the phenomenon by which the effect of a mutation depends on its genetic background. While it is usually defined in terms of organismal fitness, for single proteins, it must reflect physical interactions among residues. Here, we systematically extract the specific contribution pairwise epistasis makes to the physical affinity of antibody-antigen binding relevant to affinity maturation, a process of accelerated Darwinian evolution. We find that, among competing definitions of affinity, the binding free energy is the most appropriate to describe epistasis. We show that epistasis is pervasive, accounting for 25%-35% of variability, of which a large fraction is beneficial. This work suggests that epistasis both constrains, through negative epistasis, and enlarges, through positive

SUBMITTER: Adams RM 

PROVIDER: S-EPMC6487650 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature