title: Distributions of beneficial fitness effects in RNA.
abstract: Beneficial mutations are the driving force of evolution by natural selection. Yet, relatively little is known about the distribution of the fitness effects of beneficial mutations in populations. Recent work of Gillespie and Orr suggested some of the first generalizations for the distributions of beneficial fitness effects and, surprisingly, they depend only weakly on biological details. In particular, the theory suggests that beneficial mutations obey an exponential distribution of fitness effects, with the same exponential parameter across different regions of genotype space, provided only that few possible beneficial mutations are available to that genotype. Here we tested this hypothesis with a quasi-empirical model of RNA evolution in which fitness is based on the secondary structures of molecules and their thermodynamic stabilities. The fitnesses of randomly selected genotypes appeared to follow a Gumbel-type distribution and thus conform to a basic assumption of adaptation theory. However, the observed distributions of beneficial fitness effects conflict with specific predictions of the theory. In particular, the distributions of beneficial fitness effects appeared exponential only when the vast majority of small-effect beneficial mutations were ignored. Additionally, the distribution of beneficial fitness effects varied with the fitness of the parent genotype. We believe that correlation of the fitness values among similar genotypes is likely the cause of the departure from the predictions of recent adaptation theory. Although in conflict with the current theory, these results suggest that more complex statistical generalizations about beneficial mutations may be possible.
authors.affiliation: Institute for Cellular and Molecular Biology, University of Texas, Austin, Texas 78712, USA.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Cowperthwaite
authors.forename: J J
authors.initials: JJ
authors.lastname: Bull
authors.forename: Lauren Ancel
authors.initials: LA
authors.lastname: Meyers
mesh_terms: D019143:Evolution, Molecular; D008957:Models, Genetic; D009154:Mutation; D012313:RNA / Q000235:genetics*; D012641:Selection, Genetic
chemical_list: D012313:RNA