Intergenic incompatibilities reduce fitness in hybrids of extremely closely related bacteriophages

Horizontal gene transfer and recombination occur across many groups of viruses and play key roles in important viral processes such as host-range expansion and immune-system avoidance. To have any predictive power regarding the ability of viruses to readily recombine, we must determine the extent to which epistasis restricts the success of recombinants, particularly as it relates to the genetic divergence between parental strains. In any hybridization event, the evolutionary success or failure of hybrids is largely determined by the pervasiveness of epistasis in the parental genomes. Recombination has previously been shown to incur steep fitness costs in highly divergent viruses as a result of disrupted epistatic interactions. We used a pair of bacteriophages of the family Microviridae to demonstrate that epistasis may evidence itself in the form of fitness costs even in the case of the exchange of alleles at a locus with amino acid divergence as low as 1%. We explored a possible biophysical source of epistasis in the interaction of viral coat and scaffolding proteins and examined a recovery mutation that likely repairs interactions disrupted by recombination.