Two sides of the same coin: A population genetics perspective on lethal mutagenesis and mutational meltdown

Abstract

The extinction of RNA virus populations upon application of a mutagenic drug is frequently referred to as evidence for the existence of an error threshold, above which the population cannot sustain the mutational load. To explain the extinction process after reaching this threshold, models of lethal mutagenesis have been proposed, in which extinction is described as a deterministic (and thus population size-independent) process. As a separate body of literature, the population genetics community has developed models of mutational meltdown, which focus on the stochastic (and thus population-size dependent) processes governing extinction. However, recent extensions of both models have blurred these boundaries. Here, we first clarify definitions in terms of assumptions, expectations, and relevant parameter spaces, and then assess similarities and differences. As concepts from both fields converge, we argue for a unified theoretical framework that is focused on the evolutionary processes at play, rather than dispute over terminology.