Mutators and sex in bacteria: conflict between adaptive strategies

Abstract

Bacterial mutation rates can increase and produce genetic novelty, as shown by in vitro and in silico experiments. Despite the cost due to a heavy deleterious mutation load, mutator alleles, which increase the mutation rate, can spread in asexual populations during adaptation because they remain associated with the rare favorable mutations they generate. This indirect selection for a genetic system generating diversity (second-order selection) is expected to be highly sensitive to changes in the dynamics of adaptation. Here we show by a simulation approach that even rare genetic exchanges, such as bacterial conjugation or transformation, can dramatically reduce the selection of mutators. Moreover, drift or competition between the processes of mutation and recombination in the course of adaptation reveal how second-order selection is unable to optimize the rate of generation of novelty.

Figure 1

Genetic exchanges reduce the frequency of mutator fixation, although faster adaptation is always occurring in a mutator background. (A) Frequency of 100-fold mutator allele fixation (white) and contribution (gray) in a large population (10⁹ bacteria) (1,000 simulations per point). (B) Difference in adaptation times between mutator and antimutator backgrounds in large populations (over 200 simulations). ○, The mean adaptation time of populations with a fixed low mutation rate; □, populations with a fixed high mutation rate (100-fold higher than the previous). ▴, The mean adaptation time of populations with an initially low mutation rate that could possibly fix a 100-fold mutator during adaptation.

Figure 2

The presence of moderate mutator alleles reduces the probability of fixation of a strong mutator allele. Fixation probability (1,000 simulations per point) of a 100-fold mutator in an asexual population of 10⁹ cells is presented as a function of the strength of the moderate mutator allele fixed in the population before adaptation (mutator allele strengths are relative to wild type).

Figure 3

Population size modifies the effect of genetic exchanges on the fixation of mutators. (A) The fixation frequency (1,000 simulations per point) of a 100-fold mutator allele, with a rate of sex of 10⁻⁴ per gene per generation (▴) or without genetic exchanges (□) as a function of the population size. The effect of sex on the fate of the mutator () is the ratio of the frequency of mutator fixation without sex to the frequency of mutator fixation with sex. (B) Difference in adaptation times between mutator and antimutator backgrounds in large populations (over 200 simulations). ○, ●, The mean adaptation time of populations with a fixed low mutation rate, with a rate of sex of 10⁻⁴ per gene per generation (●) or without genetic exchanges (○). □, ■, Populations with a fixed high mutation rate (100-fold higher than the previous population) with a rate of sex of 10⁻⁴ per gene per generation (■) or without sex (□). (C) Increase in the speed of adaptation due to a mutator background or to the presence of genetic exchanges. □, The factor by which mutator background accelerates adaptation compared with nonmutator background in asexual population; ●, the factor by which genetic exchanges (at a rate of 10⁻⁴ per gene per generation) accelerate adaptation compared with asexual populations in the nonmutator background.

Figure 4

At high rates of beneficial mutations, genetic exchanges cannot prevent the fixation of mutators. The fixation probability (1,000 simulations per point) of a 100-fold mutator allele, with a rate of sex of 10⁻⁴ per gene per generation (▴) or without genetic exchanges (□). (), Ratio of the frequency of mutator fixation without sex to the frequency of mutator fixation with sex. The population size is 10⁹ bacteria.

Figure 5

Weak selection increases the effect of sex on mutator fixation. The fixation probability (1,000 simulations per point) of a 100-fold mutator allele, with a rate of sex of 10⁻⁴ per gene per generation (▴) or without genetic exchanges (□), is presented as a function of the strength of selection. All selective values of favorable alleles were multiplied by 0.5, 0.75, 1, 1.5, 2, and 3. The effect of sex on the fate of mutators () is the ratio of the frequency of mutator fixation without sex to the frequency of mutator fixation with sex. The population size is 10⁹ bacteria.