A null model for the distribution of fitness effects of mutations

Abstract

The distribution of fitness effects (DFE) of new mutations is key to our understanding of many evolutionary processes. Theoreticians have developed several models to help understand the patterns seen in empirical DFEs. Many such models reproduce the broad patterns seen in empirical DFEs but these models often rely on structural assumptions that cannot be tested empirically. Here, we investigate how much of the underlying “microscopic” biological processes involved in the mapping of new mutations to fitness can be inferred from “macroscopic” observations of the DFE. We develop a null model by generating random genotype-to-fitness maps and show that the null DFE is that with the largest possible information entropy. We further show that, subject to one simple constraint, this null DFE is a Gompertz distribution. Finally, we illustrate how the predictions of this null DFE match empirically measured DFEs from several datasets, as well as DFEs simulated from Fisher’s geometric model. This suggests that a match between models and empirical data is often not a very strong indication of the mechanisms underlying the mapping of mutation to fitness.