Distributions of Beneficial Fitness Effects in RNA

Beneficial mutations are the driving force of evolution by natural selection. Molecular biology has provided insights into the causes and types of mutations, as well as the biochemical and functional bases of specific beneficial mutations. 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 mutations and, surprisingly, they are partially biology independent. In particular, the theory suggests beneficial mutations obey an exponential distribution of fitness effects, with the same exponential parameter across different regions of genotype space, provided only that there are few possible beneficial mutations 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 theory was supported in local regions of genotype space when mildly beneficial mutations were ignored. However, the theory neither generalized to the full distribution of beneficial mutations in local regions of genotype space nor did the theory generalize across genotype space. Although in conflict with the current theory, these results suggest that more complex statistical generalizations about beneficial mutations may be possible.