Eco-evolutionary dynamics of defense systems in mobile genetic elements: Cui bono?

Background: Mobile genetic elements (MGEs), including viruses, plasmids, and transposons, are major drivers of evolution in bacteria and archaea. Host-parasite conflicts drive the emergence of a broad variety of defense and counter-defense systems. Recent advances in metagenomics and functional annotation have shown that many defense systems are located on MGEs. The fact that MGEs are, essentially, genomic parasites raises an intriguing question: why do these parasites carry defense systems at high prevalence, often even higher than the host chromosome? Results: We developed a simple mathematical model to investigate the factors that promote evolution of defense systems in MGEs and the ecological implications of MGE-encoded defense. Our analysis points to the strength of inter-MGE interference as a key determinant of the evolution of defense systems in MGEs. We identify two qualitatively distinct regimes, depending on the basic reproductive number in mixed coinfections. Weakly interfering MGEs tend to carry low-cost defense systems that enhance the survival of their hosts upon exposure to more damaging MGEs. Although these systems can be occasionally transferred to the host, they typically remain in MGEs. In contrast, strongly interfering MGEs, such as plasmids from the same incompatibility group, can carry high-cost defense systems that are detrimental to the host and the population as a whole, but help their carriers spread by actively replacing their competitors. Conclusions: Analysis of our model shows that the key determinant of the evolution and spread of defense systems in MGEs is the strength of cross-MGE interference. Weakly interfering MGEs would serve as "MGE banks", typically carrying low-cost defense systems that can benefit the host by protecting it from more damaging MGEs. In contrast, strongly interfering MGEs would carry costly defense systems that mediate inter-MGE conflicts but are deleterious to the host. These MGEs could serve as proving grounds for emerging defense systems, which might eventually become cost-effective once optimized by selection.