The effect of population bottlenecks on mutation rate evolution in asexual populations

Abstract

In the absence of recombination, a mutator allele can spread through a population by hitchhiking with beneficial mutations that appear in its genetic background. Theoretical studies over the past decade have shown that the survival and fixation probability of beneficial mutations can be severely reduced by population size bottlenecks. Here, we use computational modelling and evolution experiments with the yeast S. cerevisiae to examine whether population bottlenecks can affect mutator dynamics in adapting asexual populations. In simulation, we show that population bottlenecks can inhibit mutator hitchhiking with beneficial mutations and are most effective at lower beneficial mutation supply rates. We then subjected experimental populations of yeast propagated at the same effective population size to three different bottleneck regimes and observed that the speed of mutator hitchhiking was significantly slower at smaller bottlenecks, consistent with our theoretical expectations. Our results, thus, suggest that bottlenecks can be an important factor in mutation rate evolution and can in certain circumstances act to stabilize or, at least, delay the progressive elevation of mutation rates in asexual populations. Additionally, our findings provide the first experimental support for the theoretically postulated effect of population bottlenecks on beneficial mutations and demonstrate the usefulness of studying mutator frequency dynamics for understanding the underlying dynamics of fitness-affecting mutations.

Keywords: asexual populations; beneficial mutations; hitchhiking; mutation rate; population bottlenecks; yeast.

Figure 1. The effect of population bottlenecks on mutator dynamics at different supply rates of beneficial mutations in simulated populations

Probability of mutator fixation (solid lines) generally declined with smaller bottlenecks while the time to mutator fixation (dashed lines) increased and became more variable. Bottlenecks were particularly effective at smaller beneficial mutation supply rates. The supply rate of beneficial mutations, NU_b, was adjusted by varying the population size, N, between 10⁵ (Column 1), 10⁶ (Column 2), and 10⁷ (Column 3) individuals and beneficial mutation rate, U_b, between 10⁻⁶ (Row 1), 10⁻⁷ (Row 2), and 10⁻⁸ (Row3) mutations per individual per generation. Beneficial mutations were drawn from a exponential distribution with mean 0.05 and the mutator increased the mutation rate 50-fold. Error bars on the time to fixation represent 1 standard deviation. Results are averaged over 1000 runs of the simulation.

Figure 2. Selection strength of beneficial mutations and mutator dynamics in bottlenecked populations

Bottlenecks inhibited mutator fixation across all parameter combinations simulated. The probability of fixation (circles) declined while the average time to fixation (squares) increased faster in populations with smaller mutations. Beneficial mutations were drawn from exponential distributions with means 0.05 (solid), 0.02 (dashed), or 0.01 (dotted). All populations were propagated at N = 10⁶, while U_b varied between 10⁻⁶ (A), 10⁻⁷ (B), and 10⁻⁸ (C). The mutator increased the mutation rate 50-fold. Error bars on the time to fixation represent 1 standard deviation. Results are averaged over 1000 runs of the simulation.

Figure 3. Mutator strength and population bottlenecks

Relative fixation probabilities (circles) were calculated as the observed fixation probability over the fixation probability in a non-bottlenecked simulation. Relative average times to fixation (squares) were calculated as the observed average fixation time minus the average fixation time in a non-bottlenecked population. Relative fixation probability of a weaker 5-fold mutator (dashed) was generally lower and declined faster than that of a stronger 50-fold mutator (solid). Relative time to fixation of the 5-fold mutator (dashed) was generally greater than that of the 50-fold mutator and increased faster with smaller bottlenecks. All populations were propagated at N = 10⁶, while U_b varied between 10⁻⁶ (A), 10⁻⁷ (B), and 10⁻⁸ (C). Results are averaged over 1000 runs of the simulation.

Figure 4. Mutator dynamics in experimental populations

Asexual populations of yeast were propagated at a similar effective population size but were subjected to three different bottleneck regimes. A) Large bottlenecks - 2 mL cultures that experienced daily 1:100 dilutions. B) Medium bottlenecks - 10 mL cultures that experienced daily 1:740 dilutions. C) Small bottlenecks - 20 mL cultures that experienced daily 1: 1626 dilutions.