Site-Specific Recombination – How Simple DNA Inversions Produce Complex Phenotypic Heterogeneity in Bacterial Populations

Many bacterial species generate phenotypically heterogeneous subpopulations as a strategy for ensuring the survival of the population as a whole - an environmental stress that eradicates one subpopulation may leave other phenotypic groups unharmed, allowing the lineage to continue. Phase variation, a process that functions as an ON/OFF switch for gene expression, is one way that bacteria achieve phenotypic heterogeneity. Phase variation occurs stochastically and reversibly, and in the presence of a selective pressure the advantageous phenotype(s) predominates in the population. Phase variation can occur through multiple genetic and epigenetic mechanisms. This review focuses on conservative site-specific recombination that generates reversible DNA inversions as a genetic mechanism mediating phase variation. Recent studies have sparked a renewed interest in phase variation mediated through DNA inversion, revealing a high level of complexity beyond simple ON/OFF switching, including unusual modes of gene regulation, and highlighting an underappreciation of the use of these mechanisms by bacteria.