The underappreciated role for phase variation and quasi-clonality in microbial populations

Phase variation is a well-established phenomenon in some bacteria, where it generates heritable phenotypic variants within a population. These states, while reversible, are stable across generations, giving rise to quasi-clonal populations even when starting from a single bacterium. Underlying mechanisms include variation in short homopolymeric or heteropolymeric sequence repeats, DNA inversions mediated by site-specific recombination, reversible insertions and deletions, and switching between alternative methylation states. Although phase variation occurs in diverse bacteria, its contribution to phenotypic heterogeneity remains overlooked and use of the term is often absent in describing this phenomenon.