Life and death of an influential passenger: Wolbachia and the evolution of CI-modifiers by their hosts

Abstract

Background: Wolbachia are intracellular bacteria widely distributed among arthropods and nematodes. In many insect species these bacteria induce a cytoplasmic incompatibility (CI) between sperm of infected males and eggs of uninfected females. From an evolutionary point of view, CI is puzzling: In order to induce this modification-rescue system, Wolbachia affect sperm of infected males even though Wolbachia are only transmitted maternally. Phylogenetic studies of Wolbachia and hosts show that the bacteria rarely cospeciate with their hosts, indicating that infections are lost in host species. However, the mechanisms leading to Wolbachia loss are not well understood.

Results: Using a population genetic model, we investigate the spread of host mutants that enhance or repress Wolbachia action by affecting either bacterial transmission or the level of CI. We show that host mutants that decrease CI-levels in males (e.g. by reducing Wolbachia-density during spermatogenesis) spread, even at cost to mutant males. Increase of these mutants can lead to loss of Wolbachia infections, either as a direct consequence of their increase or in a step-wise manner, and we derive analytically a threshold penetrance above which a mutation's spread leads to extinction of Wolbachia. Selection on host modifiers is sexually antagonistic in that, conversely, host mutants that enhance Wolbachia in females are favoured whereas suppressors are not.

Conclusions: Our results indicate that Wolbachia is likely to be lost from host populations on long evolutionary time scales due to reduction of CI levels in males. This can occur either by evolution of single host modifiers with large effects or through accumulation of several modifier alleles with small effects on Wolbachia action, even at cost to mutant males and even if infected hosts do not incur fecundity costs. This possibility is consistent with recent findings and may help to explain the apparent short evolutionary persistence times of Wolbachia in many host systems.

Figure 1. Spread of male-specific cost-free repressive mutations.

This figure illustrates the two scenarios of the spread of a male-specific repressive mutation with Wolbachia either persisting (graph 1a) or going extinct (graph 1b). The graphs show the frequency of the four different classes: Dashed lines represent uninfected wild-types and dash-dot lines uninfected mutants while infected wild-types are depicted by dotted lines and infected mutants by solid lines. Penetrance levels were varied between e = 0.5 in subfigure 1a and e = 1 in subfigure 1b. Other parameters were t = 0.9, l _CI = 1, f = 0, and c = 0.

Figure 2. Parameter regions of spread of costly male-specific repressive mutations and loss of Wolbachia.

Shown are the parameter regions of a mutation's penetrance levels e and the level of CI l _CI where a male-specific repressive mutation can spread in the population, and how this affects the persistence of Wolbachia. In 2a the survival cost was set to c = 0 and the mutation could always spread. In 2b and 2c the survival cost was set to c = 0.01 and c = 0.05, respectively. Dashed lines mark the critical penetrance e _crit. as approximated analytically in eq.30 of Appendix S1. Other parameters were t = 0.9, d = 0, and f = 0.

Figure 3. Spread of costly male-specific repressive and cost-free female-specific enhancing mutations.

Shown are typical dynamics for the spread of a male-specific repressive mutation with associated survival costs and Wolbachia going extinct (3a, insert enlarged for temporal clarity), or of a female-specific enhancing mutation increasing transmission rates without survival costs (3b). Dashed lines represent uninfected wild-types and dash-dot lines uninfected mutants, while infected wild-types are depicted by dotted lines and infected mutants by solid lines. Parameters were t = 0.9, e = 1, l _CI = 1, f = 0, c = 0.05, and d = 0 in 3a and t = 0.9, e = 0, l _CI = 0.5, f = 0, c = 0, and d = 0.05 in 3b.

Figure 4. Altered Wolbachia-prevalence after spread of repressive and enhancing mutations.

Shown in 4a is the reduced prevalence of Wolbachia after successful spread of a male-specific repressive mutation. Prevalence is shown as a function of the mutation's penetrance e for different values of l _CI (as indicated in the graph) and with t = 0.95. Figure 4b shows the elevated prevalence of Wolbachia after fixation of a female-specific enhancing mutation as a function of the mutation's penetrance −d for different values of t (as indicated) with l _CI = 0.5. All plots are based on the analytical results of eqs. 33&34 and eqs. 35&36 respectively, all in Appendix S1. In 4a, e was varied between e = 0 and e = e _crit. for each case. At higher values of e, the spread of the mutation reduces Wolbachia's prevalence to zero. In 4b, −d was varied between −d = 0 and , as larger values of −d all lead to t ^eff. = 1. Other parameters were c = 0 and f = 0.

Figure 5. Parameter regions of spread of female-specific enhancing mutations.

Shown are the parameter regions of the mutation's penetrance levels d and the level of CI l _CI where a female-specific enhancing mutation that either increases transmission rates (5a and b) or increases the rescue function autonomously (5c) can spread in the population. Transmission rates were varied between t = 0.9 (5a and c) and t = 0.95 (5b). The survival cost c was varied as indicated, and the mutation could invade (and spread to fixation) above the depicted threshold lines. In 5a and c, costless mutations could always invade. Penetrance levels in 5a and b (where they take on negative values in order to increase transmission rates) were varied between −d = 0 and (where t ^eff. becomes 1) and between 0 and 1 in subfigure c. The grey line in 5c depicts the critical penetrance level d _crit. above which Wolbachia is driven to extinction by the mutation's spread. Other parameters were e = 0 and f = 0.

Figure 6. Cascades of male-specific repressive mutations and loss of Wolbachia.

Shown in 6a are the increasing fitness advantages during a cascade of male-specific repressive mutations of equally small effect. The percentage fitness benefits of an additional mutation relative to the predominating genotype are plotted against the currently fixed number of n mutations. Fitness benefits are approximated using eqs. 27–28 of Appendix S1. Each dot represents one mutational step in the cascade; stars indicate the final stop of loss of Wolbachia where cumulative effects reach the threshold penetrance e _thr.. Parameters are e = 0.025 and l _CI = 0.4 with transmission rates varied as indicated. Shown in 6b are the critical numbers of male-specific repressive mutations n _crit. of equal effect that are necessary to drive Wolbachia to extinction in such a cascade of mutations. These thresholds were calculated analytically using eq.37 of Appendix S1 and are plotted as a function of l _CI with t varied as indicated and e = 0.025. Other parameters for both graphs are c = 0 and f = 0.