show Abstracthide AbstractBacteriophage lysis is one of the main biotic causes of Synechococcus mortality in pelagic systems. However, Synechococcus populations show no extinction, suggesting high rates of production counteract this mortality, or that specific phage resistance mechanisms exist. Using the model strain Synechococcus sp. WH7803, we isolated 13 cyanophage-resistant mutants, several of which possessed 'clumping' phenotypes compared to the wild type and including three mutants in which cyanophage adsorbed to cells in a similar manner to the wild type, suggesting resistance mechanisms occur other than just modifications to the cell surface that prevent adsorption. To elucidate the molecular basis of this resistance we performed whole-genome sequencing (WGS) analysis of each mutant. This revealed that each mutant possessed a distinctive mutation profile, with > 20 unique mutations present in each isolate at a variable frequency. Such a profile is in stark contrast to previous work in the closely related Prochlorococcus genus, where specific mutations in cyanophage resistant mutants were identified at 100 % frequency. Here, we propose that the mutation profile in Synechococcus sp. WH7803 phage-resistant mutants is a function of the oligoploid nature of this bacterium. Indeed, subsequent isolation and WGS analysis of cyanophage-resistant mutants in the monoploid strain Synechococcus sp. WH7805 revealed a profile similar to Prochlorococcus. The mutation profile of Synechococcus sp. WH7803 mutants suggests that ploidy plays an underlying role in bacteriophage resistance in this organism, albeit by an, as yet, unknown mechanism(s).