Frank, S. A. 1994. Polymorphism of bacterial restriction-modification systems: the advantage of diversity. Evolution 48:1470-1477.

Bacterial restriction-modification systems provide defense against foreign DNA by using a self versus nonself recognition mechanism. A great diversity of recognition motifs are maintained in natural populations. Circumstantial evidence suggests that defense against bacteriophage viruses favors this diversity. (1) Bacterial restriction enzymes can destroy invading phage DNA. (2) Phage DNA can mimic the host's self-recognition mechanism. The ability of the virus to pose as a mimic favors diversification of the host's recognition motif. Other observations suggest that restriction-modification (RM) does not provide any significant defensive advantages in mature communities. (1) In laboratory experiments, bacteria evolve resistance to phage by mutation and selection of the receptors to which phage adsorb. The outcome of these experiments is a community dominated by bacteria with receptor-based resistance, with a low abundance of phage and susceptible bacteria. (2) Phage are rare and receptor-based resistance is common in samples from natural communities. I present a model that shows two factors determine community composition: resources and RM diversity. Communities in resource-rich habitats are dominated by receptor-based resistance and support few phage; communities in poor habitats are dominated by restriction-modification defense and relatively abundant phage. RM diversity is itself a direct cause of community composition. As diversity increases from a low level, the abundance of phage increases and the relative abundance of receptor-based resistance declines. Further increases in diversity cause a crash in phage abundance, yielding a stable community of diverse RM types but an absence of the selective pressure—the phage—that drove the diversification. Empirical studies must sample a range of resource levels and RM diversity to analyze the forces that determine community composition.