title: REVIEW: Epistasis and dominance in the emergence of catalytic function as exemplified by the evolution of plant terpene synthases.
abstract: 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.
authors.affiliation: John Innes Centre, Computational and Systems Biology, Norwich Research Park, Norwich NR4 7UH, UK. Electronic address: Jitender.Cheema@jic.ac.uk.
authors.forename: Jitender
authors.initials: J
authors.lastname: Cheema
authors.affiliation: John Innes Centre, Department of Metabolic Biology, Norwich Research Park, Norwich NR4 7UH, UK. Electronic address: FaraldosJA@cardiff.ac.uk.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Faraldos
authors.affiliation: John Innes Centre, Department of Metabolic Biology, Norwich Research Park, Norwich NR4 7UH, UK; Institute of Food Research, Food & Health Programme, Norwich Research Park, Norwich NR4 7UA, UK. Electronic address: paul.omaille@sri.com.
authors.forename: Paul E
authors.initials: PE
authors.lastname: O'Maille
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000235:genetics* / Q000378:metabolism; D005075:Biological Evolution; D004843:Epistasis, Genetic; D017343:Genes, Plant; D008954:Models, Biological; D009154:Mutation; D010641:Phenotype; D010940:Plant Proteins / Q000235:genetics* / Q000378:metabolism; D010944:Plants / Q000235:genetics* / Q000378:metabolism; D011487:Protein Conformation; D013729:Terpenes / Q000378:metabolism*
chemical_list: D010940:Plant Proteins; D013729:Terpenes; D019883:Alkyl and Aryl Transferases; C108877:terpene synthase
keywords: Chemical mechanisms; Epistasis; Evolutionary theory; Networks; Plant specialized metabolism; Protein structure