Epistasis in protein evolution

The structure, function, and evolution of proteins depend on physical and genetic interactions among amino acids. Recent studies have used new strategies to explore the prevalence, biochemical mechanisms, and evolutionary implications of these interactions-called epistasis-within proteins. Here we describe an emerging picture of pervasive epistasis in which the physical and biological effects of mutations change over the course of evolution in a lineage-specific fashion. Epistasis can restrict the trajectories available to an evolving protein or open new paths to sequences and functions that would otherwise have been inaccessible. We describe two broad classes of epistatic interactions, which arise from…

• NS
  National Science Foundation

  Awards: DGE‐1144082, 1144082, DGE-1144082
• NI
  National Institutes of Health

  Awards: DGE-1144082, T32-GM007183, R01GM104397, T32‐GM007183