Allopatric divergence of cooperators confers cheating resistance and limits effects of a defector mutation.

Background: Social defectors may meet diverse cooperators. Genotype-by-genotype interactions may constrain the ranges of cooperators upon which particular defectors can cheat, limiting cheater spread. Upon starvation, the soil bacterium Myxococcus xanthus cooperatively develops into spore-bearing fruiting bodies, using a complex regulatory network and several intercellular signals. Some strains (cheaters) are unable to sporulate effectively in pure culture due to mutations that reduce signal production but can exploit and outcompete cooperators within mixed groups.

Results: In this study, interactions between a cheater disrupted at the signaling gene csgA and allopatrically diversified cooperators reveal a very small cheating range. Expectedly, the cheater failed to cheat on all natural-isolate cooperators owing to non-cheater-specific antagonisms. Surprisingly, some lab-evolved cooperators had already exited the csgA mutant's cheating range after accumulating fewer than 20 mutations and without experiencing cheating during evolution. Cooperators might also diversify in the potential for a mutation to reduce expression of a cooperative trait or generate a cheating phenotype. A new csgA mutation constructed in several highly diverged cooperators generated diverse sporulation phenotypes, ranging from a complete defect to no defect, indicating that genetic backgrounds can limit the set of genomes in which a mutation creates a defector.

Conclusions: Our results demonstrate that natural populations may feature geographic mosaics of cooperators that have diversified in their susceptibility to particular cheaters, limiting defectors' cheating ranges and preventing them from spreading. This diversification may also lead to variation in the phenotypes generated by any given cooperation-gene mutation, further decreasing the chance of a cheater emerging which threatens the persistence of cooperation in the system.