The coevolution of toxin and antitoxin genes drives the dynamics of bacterial addiction complexes and intragenomic conflict

Abstract

Bacterial genomes commonly contain ‘addiction’ gene complexes that code for both a toxin and a corresponding antitoxin. As long as both genes are expressed, cells carrying the complex can remain healthy. However, loss of the complex (including segregational loss in daughter cells) can entail death of the cell. We develop a theoretical model to explore a number of evolutionary puzzles posed by toxin–antitoxin (TA) population biology. We first extend earlier results demonstrating that TA complexes can spread on plasmids, as an adaptation to plasmid competition in spatially structured environments, and highlight the role of kin selection. We then considered the emergence of TA complexes on plasmids from previously unlinked toxin and antitoxin genes. We find that one of these traits must offer at least initially a direct advantage in some but not all environments encountered by the evolving plasmid population. Finally, our study predicts non-transitive ‘rock-paper-scissors’ dynamics to be a feature of intragenomic conflict mediated by TA complexes. Intragenomic conflict could be sufficient to select deleterious genes on chromosomes and helps to explain the previously perplexing observation that many TA genes are found on bacterial chromosomes.

The Toxin–Antidote Model of Cytoplasmic Incompatibility: Genetics and Evolutionary Implications

“…In brief, the idea is that TA systems make themselves addictive as soon as they enter a cell: the toxin molecule is typically more stable than the antidote, such that removing the source of both results in cell death. Although this property is not necessarily invasive (an element killing a host once it is lost increases its effective transmission rate but will not, by itself, increase its frequency), it can promote invasion under some circumstances, especially if the TA system is part of a horizontally transmitted mobile genetic element [64].…”

Antibiotic resistance shaping multi-level population biology of bacteria

“…Plasmid-mediated common benefits will probably lead to GEC-plasmid coevolution (Skippington and Ragan, 2012). Along the same line, addiction-type TA complexes can spread on plasmids, favoring coexistence and/or competition in spatially structured environments (Rankin et al, 2012) highlighting the role of kin effects in GECs selection (taking “kin” in a wider sense than just intra-specific ties). It is of note, however, that possibly most organisms and environments might act as conduits for resistance gene flow (Stokes and Gillings, 2011), acting as “sources” from where resistance genes are directed to GECs, acting as “sinks,” according to the Perron et al (2007) metaphor.…”

Evolutionary Pathways and Trajectories in Antibiotic Resistance

“…Plasmid-encoded TA systems have an advantage in within-host plasmid competition if the host cell is sensitive to the toxin(948). Long-term coevolution of a plasmid in a particular species can result in partially or fully codependent replicons, a "plasmid specialization in particular species", limiting the spread to other lineages in which the maintenance or expression of plasmid traits, such as ARGs, could be reduced(748,949).Most bacterial species tend to diverge into subspecies and clones by the process of "clonalization" (mimicking speciation by adaptation frequently mediated by HGT) to neighboring ecological niches (ecovars). This ecological neighborhood facilitates the evolution of plasmid-host specificity, frequently overcoming the process of clonalization(950).…”