The evolution of a condition-dependent mutation rate enhances evolvability

Empirical studies have demonstrated that mutation rates may change with individual condition, such as in the case of stress-induced mutagenesis. This has led to the hypothesis that condition-dependent (or "plastic") mutation rates could be selectively favoured, as the increased production of new mutants in times of maladaptation enhances evolvability, the ability to undergo adaptive evolution. However, while empirical evidence for condition-dependent mutation rates is accumulating, theoretical models studying their evolution are lacking. Here, we employ an individual-based simulation approach to examine the evolution of condition-dependent mutation rates in a changing environment. We find that condition-dependent mutation rates consistently evolve when the environment changes at an intermediate pace. Furthermore, populations with condition-dependent mutation rates are substantially better adapted to their (changing) environment. Finally, the evolutionary dynamics of condition-dependent mutation rates are both accelerated and destabilised when the mutation rate is self-referential (i.e., when mutator loci affect their own mutation rate). We conclude that condition-dependent mutation rates (and thus evolvability) can readily evolve in changing environments. Significance statementMutation provides the raw material for evolution. Mutation rates thus tune evolvability, the ability to undergo adaptive evolution: if mutation rates are too low, evolution is impeded; if mutation rates are too high, adaptive traits cannot be maintained. Using a theoretical model, we explore the evolution of plastic mutation rates that systematically depend on the condition of the organism and its environment. An example is stress-induced mutagenesis in bacteria, which is implicated in the evolution of antibiotic resistance. We show that plastic mutation rates readily evolve, providing "well-timed" variation specifically when organisms are poorly adapted. Such plastic mutation rates thus facilitate better adaptation to changing environments, and their evolution provides an example of evolvability itself evolving.