GENETIC HURDLES LIMIT THE ARMS RACE BETWEEN PROCHLOROCOCCUS AND THE PODOVIRUSES INFECTING THEM

Members of the abundant marine Prochlorococcus genus coexist with their cyanophage parasites. Genetic data suggest that each cyanophage type can only infect a small fraction of the Prochlorococcus population. How then do cyanophages survive on this seemingly small host population? Coexistence through a coevolutionary arms race requires phage mutants to overcome resistance of their hosts, yet little is known of the prevalence of such resistance-breaking mutants and their effect on phage genomes and fitness.

To test the relevance of the mutational arms-race model for Prochlorococcus and their phages we screened T7-like cyanopodophage populations for resistance-breaking mutants that infect previously isolated phage-resistant Prochlorococcus strains. Two phenotypic classes were found among phage mutants: either those with a small fitness gain on both their original and new hosts; or a large fitness gain on the new host accompanied by a cost of decreased specificity.

Mutations were in genes likely involved in tail assembly and structure. Exploration of other T7-like cyanophage genomes and viral metagenomes revealed enhanced phage genomic diversity in the resistance-breaking genes identified in this study. Hypervariability in resistance and resistance-breaking loci in hosts and phages, respectively, stand testimony to an ongoing evolutionary arms race between these antagonists.

However, cyanopodophage resistance-breaking mutants were rare or undetectable in most interactions. Such phage resistance mutations of Prochlorococcus that cannot be overcome by phage resistance-breaking mutations pose genetic hurdles that impede the progression of the arms race. Therefore, we propose that host-phage coexistence in this system is enabled by fluctuating selection dynamics involving fitness costs on both sides and passive host switching in addition to a slow arms race that increases diversity of both hosts and phages.