title: Effects of genotype on rates of substitution during experimental evolution.
abstract: Rates of molecular evolution may vary widely between populations, yet the causes of this variation are still incompletely understood. Genetic differences between populations may make an important contribution to variation in rates of evolution, owing to differences in fitness, population size, mutation rates, or in the distribution of fitness effects (DFEs) of available beneficial mutations. By whole genome sequencing of Escherichia coli populations experimentally evolved in the presence of a quinolone antibiotic, we found that rates of substitution varied by genotype, with evidence for a contribution from a genotype's starting fitness. Subsequent targeted sequencing showed that genotypes with high average substitution rates were more likely to undergo the simultaneous fixation of several mutations, consistent with theoretical models of multiple mutation dynamics. Moreover, patterns of substitution were indicative of epistatic relationships between known resistance mutations.
authors.affiliation: Department of Biology, Carleton University, Ottawa, Ontario, Canada. alex.wong@carleton.ca.
authors.forename: Alex
authors.initials: A
authors.lastname: Wong
authors.affiliation: Department of Biology, Carleton University, Ottawa, Ontario, Canada.
authors.forename: Kimberley
authors.initials: K
authors.lastname: Seguin
mesh_terms: D004926:Escherichia coli / Q000235:genetics*; D019143:Evolution, Molecular; D005838:Genotype; D009154:Mutation; D012641:Selection, Genetic
keywords: Epistasis; molecular evolution; selection-experimental; variation