The evolution of a counter-defense mechanism in a virus constrains its host range

Abstract

Bacteria use diverse immunity mechanisms to defend themselves against their viral predators, bacteriophages. In turn, phages can acquire counter-defense systems, but it remains unclear how such mechanisms arise and what factors constrain viral evolution. Here, we experimentally evolved T4 phage to overcome a phage-defensive toxin-antitoxin system, toxIN, in E. coli. Through recombination, T4 rapidly acquires segmental amplifications of a previously uncharacterized gene, now named tifA, encoding an inhibitor of the toxin, ToxN. These amplifications subsequently drive large deletions elsewhere in T4s genome to maintain a genome size compatible with capsid packaging. The deleted regions include accessory genes that help T4 overcome defense systems in alternative hosts. Thus, our results reveal a trade-off in viral evolution; the emergence of one counter-defense mechanism can lead to loss of other such mechanisms, thereby constraining host range. We propose that the accessory genomes of viruses reflect the integrated evolutionary history of the hosts they infected. HighlightsO_LIExperimentally evolved T4 to overcome E. coli toxIN, a phage-defensive TA system C_LIO_LIDiscovered TifA, a phage-encoded protein inhibitor of ToxN C_LIO_LIAmplification of the tifA locus drives large deletions elsewhere in the T4 genome C_LIO_LIDeleted genes in evolved T4 clones include those necessary to infect alternative hosts C_LI