Fixation probability of a nonmutator in a large population of asexual mutators

Abstract

In an adapted population of mutators in which most mutations are deleterious, a nonmutator that lowers the mutation rate is under indirect selection and can sweep to fixation. Using a multitype branching process, we calculate the fixation probability of a rare nonmutator in a large population of asexual mutators. We show that when beneficial mutations are absent, the fixation probability is a nonmonotonic function of the mutation rate of the mutator: it first increases sublinearly and then decreases exponentially. We also find that beneficial mutations can enhance the fixation probability of a nonmutator. Our analysis is relevant to an understanding of recent experiments in which a reduction in the mutation rates has been observed.

Shifts in mutation spectra enhance access to beneficial mutations

“…We also uncover why pervasive mutation biases might evolve, complementing emerging understanding of conditions when such biases can alter adaptation (29,30). Our results have clear implications for the evolutionary dynamics of mutators, which are governed by their genetic load and supply of beneficial mutations (24,31,32). In a new environment (away from fitness optima), these parameters are primarily driven by mutators' high mutation rate (33) -particularly under strong selection (34) -allowing them to hitchhike with beneficial mutations (35).…”

Mutation bias and GC content shape antimutator invasions

“…First, the simulations purposely focused on the effects of mutational spectra on deleterious mutations, leaving aside the complications of considering either compensatory or generally-beneficial mutations. While previous research has already studied the importance of these types of mutations on antimutator dynamics 12,26,27 , a full treatment of this problem should include the fact that spectrum-driven differences can also bias mutator access to both compensatory and generally-beneficial mutations. Second, the dynamics can be further complicated by considering two phenomena well-known to limit the evolution of mutation rates: recombination and the cost of fidelity 1 .…”

“…Recent theoretical work has begun to provide a framework to account for these contrasting patterns, emphasising the role of several factors in determining the fixation probability of antimutator alleles. These factors include differences in population size, beneficial and deleterious mutation rates, mutator strength, and the availability of secondary mutations compensating the cost of deleterious mutations 12,26,27 .…”

Interference Effects of Deleterious and Beneficial Mutations in Large Asexual Populations

“…However, it is possible to make analytical progress if one exploits the fact that besides the fixation probability p i , all the mutation rates and selection coefficients are also smaller than one (Jain and James, 2017). On expanding (1) in a power series about these small quantities and retaining terms to quadratic orders (see Appendix A for details), we obtain the following equation for the fixation probability,…”

“…To find the fixation probability of a beneficial mutant for λ ≫ 1 and finite µ/λ, we essentially follow the treatment in Jain and James (2017). We first note that when the background mutation i ∼ λ, the second term on the lefthand side (LHS) of (8) may be ignored.…”