Selection on mutators is not frequency-dependent

Abstract The evolutionary fate of mutator mutations – i.e., genetic variants that raise the genome-wide mutation rate – in asexual populations is often described as being frequency (or number) dependent. This common intuition suggests that mutators can invade a population by hitchhiking with a sweeping beneficial mutation, but only when sufficiently frequent to produce such a mutation before non-mutators do. Here, we use stochastic, agent-based simulations to show that neither the strength nor the sign of selection on mutators depend on their initial frequency, and while the overall probability of hitchhiking increases predictably with frequency, the per-capita probability of fixation remains unchanged.