On the feasibility of saltational evolution

Significance In evolutionary biology, it is generally assumed that evolution occurs in the weak mutation limit, that is, the frequency of multiple mutations simultaneously occurring in the same genome and the same generation is negligible. We employ mathematical modeling to show that, although under the typical parameter values of the evolutionary process the probability of multimutational leaps is indeed low, they might become substantially more likely under stress, when the mutation rate is dramatically elevated. We hypothesize that stress-induced mutagenesis in microbes is an evolvable adaptive strategy. Multimutational leaps might matter also in other cases of substantially increased mutation rate, such as growing tumors or evolution of primordial replicators. Is evolution always gradual or can it make leaps? We examine a mathematical model of an evolutionary process on a fitness landscape and obtain analytic solutions for the probability of multimutation leaps, that is, several mutations occurring simultaneously, within a single generation in 1 genome, and being fixed all together in the evolving population. The results indicate that, for typical, empirically observed combinations of the parameters of the evolutionary process, namely, effective population size, mutation rate, and distribution of selection coefficients of mutations, the probability of a multimutation leap is low, and accordingly the contribution of such leaps is minor at best. However, we show that, taking sign epistasis into account, leaps could become an important factor of evolution in cases of substantially elevated mutation rates, such as stress-induced mutagenesis in microbes. We hypothesize that stress-induced mutagenesis is an evolvable adaptive strategy.