Mitotic recombination counteracts the benefits of genetic segregation

Abstract

The ubiquity of sexual reproduction despite its cost has lead to an extensive body of research on the evolution and maintenance of sexual reproduction. Previous work has suggested that sexual reproduction can substantially speed up the rate of adaptation in diploid populations, because sexual populations are able to produce the fittest homozygous genotype by segregation and mating of heterozygous individuals. In contrast, asexual populations must wait for two rare mutational events, one producing a heterozygous carrier and the second converting a heterozygous to a homozygous carrier, before a beneficial mutation can become fixed. By avoiding this additional waiting time, it was shown that the benefits of segregation could overcome a twofold cost of sex. This previous result ignores mitotic recombination (MR), however. Here, we show that MR significantly hastens the spread of beneficial mutations in asexual populations. Indeed, given empirical data on MR, we find that adaptation in asexual populations proceeds as fast as that in sexual populations, especially when beneficial alleles are partially recessive. We conclude that asexual populations can gain most of the benefit of segregation through MR while avoiding the costs associated with sexual reproduction.

Figure 1

Spread of a beneficial mutation in a diploid (a) sexual and (b) asexual population as a function of time. T₁ and T₂ are the first and second time lags, respectively. T_Aa and T_AA are the times to fixation of the heterozygotes (Aa) and homozygotes (AA) within an asexual population after these genotypes appear and survive stochastic loss while rare. T_A is the time to fixation of the A allele in a sexual population, assuming that the allele has survived stochastic loss.

Figure 2

Mitotic recombination can result in the loss of heterozygosity at a particular locus. Alleles A and a are represented by black and white boxes, respectively; the diamond marks the centromere on the chromosome. (a) A cell with genotype Aa replicates its DNA. (b) Mitotic recombination occurs between homologous chromosomes. (c) Depending on the alignment of chromosomes, mitotic recombination can lead to the loss of heterozygosity (AA and aa; top half) or restore heterozygosity (Aa; bottom half). We count only those mitotic recombination events resulting in loss of heterozygosity (top half), which occur at rate r.

Figure 3

The observed rate of mitotic recombination rises as a function of the distance to the centromere (data from table 1). The arrow marks the average distance to the centromere across the entire genome of S. cerevisiae. The mitotic recombination rate, r, given by the best linear fit to the untransformed data was r≈3.8×10⁻⁷δ (significance of slope p<0.0001), where δ is the distance to the centromere in kilobases. (The regression was fitted through the data on a linear–linear scale with an intercept forced through zero. Allowing the intercept to vary yields similar results.)

Figure 4

Life cycle of an asexual population with selection, mutation and mitotic recombination.

Figure 5

Spread of a beneficial allele as a function of time for different values of mitotic recombination in sexual (dashed) and asexual (solid) populations. The value above each trajectory corresponds to the rate of mitotic recombination. Each trajectory describes the time taken for the allele frequency to first rise above 0.01, 0.02, 0.03, …, 0.99, averaged across 2000 stochastic simulations with (a) s=0.1, (b) s=0.05 and (c) s=0.01. The bars represent 95% confidence intervals for the fixation time. Other parameters: h=1/2, μ=10⁻⁷, N=10⁵.

Figure 6

Fixation time of the beneficial allele as a function of mitotic recombination for selection coefficients of (a) 0.1, (b) 0.05 and (c) 0.01. Using electronic supplementary material equation (A 4) for σ, electronic supplementary material equations (A 14) and (A 15) were used to predict the time to fixation in an asexual (solid curve) and sexual (dashed) population, respectively. The circles give the simulated fixation times in sexual (hollow) and asexual (filled) populations based on 2000 replicates; the bars represent 95% confidence intervals. Other parameters: h=1/2, μ=10⁻⁷, N=10⁵.

Figure 7

Fixation time of the beneficial allele as a function of mitotic recombination for dominance coefficients of (a) 0.1 and (b) 0.9. Using electronic supplementary material equation (A 4) for σ, electronic supplementary material equations (A 14) and (A 15) were used to predict the time to fixation in an asexual (solid curve) and sexual (dashed) population, respectively. The circles give the simulated fixation times in sexual (hollow) and asexual (filled) populations based on 2000 replicates; the bars represent 95% confidence intervals. Other parameters: s=0.1, μ=10⁻⁷, N=10⁵.