Beyond clonality: invertons as engines of phenotypic heterogeneity in bacteria

Abstract One of the biggest misconceptions about clonal bacterial populations is that all members act identically. In fact, microbiologists have known for decades that genetically identical populations of bacteria are capable of reproducibly generating subgroups with differential gene expression. In this perspective, I highlight invertons, one of the many preprogrammed mechanisms that bacteria use to generate heterogeneity. Invertons are small invertible elements encoded in DNA that are flipped reversibly by an enzyme called an invertase. Flipping of these regions can turn on or off transcription of adjacent gene regions, recode proteins, or change protein specificity. While these elements have been studied for decades in a small number of bacteria, analyses of next-generation sequencing datasets have recently revealed how widespread these elements are in prokaryotes. These findings expand our knowledge of how invertons affect microbial physiology and lifestyle. Here, I discuss new data in the inverton field, highlight open questions, and emphasize how invertons and other heterogeneity generating elements fundamentally shift our views of “clonal” populations on an individual and group level.