Evolutionary entanglement of mobile genetic elements and host defence systems: guns for hire

All cellular life forms are afflicted by diverse genetic parasites, including viruses and other types of mobile genetic elements (MGEs), and have evolved multiple, diverse defence systems that protect them from MGE assault via different mechanisms. Here, we provide our perspectives on how recent evidence points to tight evolutionary connections between MGEs and defence systems that reach far beyond the proverbial arms race. Defence systems incur a fitness cost for the hosts; therefore, at least in prokaryotes, horizontal mobility of defence systems, mediated primarily by MGEs, is essential for their persistence. Moreover, defence systems themselves possess certain features of selfish elements. Common components of MGEs, such as site-specific nucleases, are 'guns for hire' that can also function as parts of defence mechanisms and are often shuttled between MGEs and defence systems. Thus, evolutionary and molecular factors converge to mould the multifaceted, inextricable connection between MGEs and anti-MGE defence systems. Incessant encounters of all cellular life forms with mobile genetic elements (MGEs) have driven the evolution of diverse defence mechanisms, including CRISPR-Cas and restriction-modification systems. In this Perspective, Koonin, Makarova, Wolf and Krupovic describe the surprisingly intricate interplay between MGEs and host defence systems. Not only do defence systems commonly show high horizontal mobility but many molecular components are 'guns for hire' that have been co-opted by defence systems from MGEs and vice versa.