Equalization of the inverted repeat sequences of the pseudorabies virus genome by intermolecular recombination.

During a study designed to identify changes in the genomes that are observed in mutant populations of pseudorabies virions, a thymidine kinase-defective population of virions which contains genomes that possess inverted repeated sequences of unequal sizes has been identified. This population of virions has been used to ascertain the mechanism and rates of equalization of the repeats. Results showed that when the virions were passed in cell cultures at high multiplicities of infection (either once or several times), one-half of the molecules had repeats of equal size and one-half had repeats of unequal size. This result is to be expected if conditions allowing a high degree of intermolecular recombination involving exchange of repeats exist. The process of intermolecular exchange of inverted repeats is rapid and the DNA molecules were at equilibrium by the time a virion had produced a small plaque. If the virions were passed in cell culture at low multiplicities of infection, they acquired genomes with equal-size repeats. This is probably due to segregation of the virions which had acquired genomes with equal repeats by recombination; in the absence of coinfection of the cells with virions containing genomes with different repeat sizes, heterogeneity of the repeats could not be generated. The fact that virions containing genomes with equal repeats are usually isolated from nature can thus be attributed to equalization of the repeats which results from intermolecular recombination, followed by segregation. A special mechanism ensuring equalization of repeats, such as one repeat acting as a template for the synthesis (or repair) of the other, need therefore not be invoked.