Review articleREVIEW: Epistasis and dominance in the emergence of catalytic function as exemplified by the evolution of plant terpene synthases

- An experimental approach to isolating epistatic networks is presented.
- Theoretical approaches to quantifying epistasis are enumerated.
- Biophysical models of protein epistasis are described.
- A speculative scenario of epistasis and dominance in catalytic function is described.
- A synthesis of evolutionary theory and mechanistic enzymology is presented.

Epistasis, the interaction between mutations and the genetic background, is a pervasive force in evolution that is difficult to predict yet derives from a simple principle − biological systems are interconnected. Therefore, one effect may be intimately linked to another, hence interdependent. Untangling epistatic interactions between and within genes is a vibrant area of research. Deriving a mechanistic understanding of epistasis is a major challenge. Particularly, elucidating how epistasis can attenuate the effects of otherwise dominant mutations that control phenotypes. Using the emergence of terpene cyclization in specialized metabolism as an excellent example, this review describes the process of discovery and interpretation of dominance and epistasis in relation to current efforts. Specifically, we outline experimental approaches to isolating epistatic networks of mutations in protein structure, formally quantifying epistatic interactions, then building biochemical models with chemical mechanisms in efforts to achieve an understanding of the physical basis for epistasis. From these models we describe informed conjectures about past evolutionary events that underlie the emergence, divergence and specialization of terpene synthases to illustrate key principles of the constraining forces of epistasis in enzyme function.

250