title: The length scale of selection in protein evolution.
abstract: Central to the study of molecular evolution, and an area of long-standing debate, is the appropriate model for the fitness landscape of proteins. Much of this debate has focused on the strength and frequency of positive and purifying selection, but the form and frequency of selective correlations is also a vital element. The constituent amino acids within a protein generically interact and share selective pressures in predictable ways, which conflicts with the selective independence assumed by common caricatures of the fitness landscape. Here, I discuss a recent study by myself and coauthors that used whole-genome comparisons of orthologous molecular sequences from closely related Drosophilids to explore the form of the selective correlations and selective interactions (epistasis) between the amino acids within a protein. I outline our results and highlight our finding of a selective length scale of ten amino acids within which individual amino acids are substantially and generically more likely to share selective pressures and interact epistatically. I then focus on the evidence presented in our study supporting a substantial role for epistasis in the process of molecular evolution, and discuss further the implications of this widespread epistasis on the overdispersion of the molecular clock and the efficacy of common tests for positive selection.
authors.affiliation: Department of Applied Physics, Stanford University, Stanford, CA, USA. benjc@stanford.edu
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Callahan
mesh_terms: D000818:Animals; D004330:Drosophila; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics*; D004331:Drosophila melanogaster; D019143:Evolution, Molecular; D012641:Selection, Genetic
chemical_list: D029721:Drosophila Proteins