Evidence for Toxin-Encoding Coinfections Driving Intransitive Dynamics Between Allelopathic Phenotypes in Natural Yeast Populations

Competitive intransitivity -- non-hierarchical interactions, such as those exemplified by the rock-paper-scissors game, where no single competitor wins outright -- has been proposed as a key mechanism for maintaining biodiversity; however, empirical evidence supporting the importance of intransitivity remains limited. Natural populations of Saccharomyces cerevisiae often include strains harboring totivirus-satellite coinfections that encode a lethal toxic glycoprotein capable of eliminating competing yeast strains. Killer strains are sparsely distributed in natural populations, despite their competitive advantage. Yeast isolates occasionally exhibit toxin resistance, but it remains untested whether they can outcompete and replace killer strains. Similarly, the persistence of toxin-susceptible yeast is not well understood --particularly whether they can invade resistant populations in the absence of killers, thereby completing an intransitive loop. In a multi-year collection of yeast isolates from vineyards across New Zealand, we observed a near-complete disappearance of a previously common killer yeast genotype of S. cerevisiae over consecutive years. Using space-time-shift competition assays, we demonstrate that strains sympatric to this killer genotype were ubiquitously resistant, unlike the allopatric strains that were frequently eliminated in competition assays. Furthermore, the extinction of the focal killer genotype appears to have enabled the emergence of toxin-susceptible competitors in sites formerly occupied by the killer genotype. Our findings suggest that the competitive advantage of toxin production is evident in natural populations but appears to be eroded when resistance evolves in competitors of the focal killer genotype. We suggest that such killer-resistant-susceptible polymorphisms are being maintained by evolutionary dynamics akin to rock-paper-scissors-like intransitivity, driven by the invasion of susceptible strains after costly resistance has driven killer strains to extinction in natural populations, all being driven by toxin-encoding coinfections.