title: The evolutionarily stable distribution of fitness effects.
abstract: The distribution of fitness effects (DFE) of new mutations is a key parameter in determining the course of evolution. This fact has motivated extensive efforts to measure the DFE or to predict it from first principles. However, just as the DFE determines the course of evolution, the evolutionary process itself constrains the DFE. Here, we analyze a simple model of genome evolution in a constant environment in which natural selection drives the population toward a dynamic steady state where beneficial and deleterious substitutions balance. The distribution of fitness effects at this steady state is stable under further evolution and provides a natural null expectation for the DFE in a population that has evolved in a constant environment for a long time. We calculate how the shape of the evolutionarily stable DFE depends on the underlying population genetic parameters. We show that, in the absence of epistasis, the ratio of beneficial to deleterious mutations of a given fitness effect obeys a simple relationship independent of population genetic details. Finally, we analyze how the stable DFE changes in the presence of a simple form of diminishing-returns epistasis.
authors.affiliation: Department of Organismic and Evolutionary Biology and FAS Center for Systems Biology, Harvard University, Cambridge, Massachusetts 02138.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Rice
authors.affiliation: Department of Organismic and Evolutionary Biology and FAS Center for Systems Biology, Harvard University, Cambridge, Massachusetts 02138 Department of Physics, Harvard University, Cambridge, Massachusetts 02138.
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Good
authors.affiliation: Department of Organismic and Evolutionary Biology and FAS Center for Systems Biology, Harvard University, Cambridge, Massachusetts 02138 Department of Physics, Harvard University, Cambridge, Massachusetts 02138 mdesai@oeb.harvard.edu.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Desai
mesh_terms: D004843:Epistasis, Genetic; D019143:Evolution, Molecular; D056084:Genetic Fitness; D006238:Haploidy; D008957:Models, Genetic; D009154:Mutation; D012641:Selection, Genetic
keywords: distribution of fitness effects; evolutionary equilibrium; mutation–selection–drift balance