The evolution and population dynamics of bacterial addiction complexes

Bacterial genomes comprise an assortment of cooperative and self-interested replicating entities (replicons). The ecology of these replicating entities most likely determines the short-term evolution of bacterial genomes. Plasmids, genetic parasites of bacteria, are ubiquitous vectors of microbial genes and are responsible for the dissemination of clinically important determinants such as antibiotic resistance. Despite their importance, there is no consistent understanding of what makes a ‘successful’ plasmid. Plasmids can reproduce infectiously between hosts by conjugation (horizontal transfer) and in synchrony with the host (vertical transfer). Their persistence is thought to rely upon a trade-off between horizontal and vertical transfer, where some plasmids persist as infectious but virulent elements, while others persist as immobile mutualists that resemble secondary chromosomes. As such, plasmids can have genes of varying usefulness to the host in which they may be found at any given time. This range of usefulness varies from harmful to beneficial through to cooperative traits. A peculiar phenotype of many plasmids is post-segregational killing, where the cell is killed upon loss of the plasmid. Killing is mediated by addiction gene complexes, which comprise both a toxin and a cognate antitoxin gene. As long as both genes are expressed, cells carrying the complex remain healthy, however, loss of the complex usually entails death of the cell. Intriguingly, addiction complexes are a ubiquitous feature of bacterial replicons and are found with near uniformity across chromosomes and plasmids. The ubiquitous presence of addiction complexes on bacterial replicons poses an intriguing evolutionary conundrum, namely, how can a trait whose principal phenotype, host-killing, be so pervasive? This thesis explores how addiction complexes affect the population dynamics of chromosomes and plasmids that carry them. We developed and analysed mathematical models of three interesting cases of addiction complex population biology: 1. the emergence of coupled toxin antitoxin gene complexes and intragenomic conflict, 2. within-host competition between competing plasmids, 3. punishment of segregating non-cooperative alleles. Collectively, these three cases examine emergence at the level of the operon, replicon (chromosome and plasmid) and community (i.e. sociobiological traits). The theoretical models developed herein were novel in their approach owing to their focus on the ecology of replicons (i.e. population dynamics of plasmids, chromosomes and phage). This replicon-centric approach allowed us to examine adaptation at the level of the replicon, which in turn generated novel hypotheses as to how addiction complexes may drive bacterial genome dynamics. Importantly, each model developed herein qualitatively predicted many observed behaviours that existing models do not