Distribution of spontaneous mutants and inferences about the replication mode of the RNA bacteriophage phi6

Abstract

When a parent virus replicates inside its host, it must first use its own genome as the template for replication. However, once progeny genomes are produced, the progeny can in turn act as templates. Depending on whether the progeny genomes become templates, the distribution of mutants produced by an infection varies greatly. While information on the distribution is important for many population genetic models, it is also useful for inferring the replication mode of a virus. We have analyzed the distribution of mutants emerging from single bursts in the RNA bacteriophage phi6 and find that the distribution closely matches a Poisson distribution. The match suggests that replication in this bacteriophage is effectively by a stamping machine model in which the parental genome is the main template used for replication. However, because the distribution deviates slightly from a Poisson distribution, the stamping machine is not perfect and some progeny genomes must replicate. By fitting our data to a replication model in which the progeny genomes become replicative at a given rate or probability per round of replication, we estimated the rate to be very low and on the on the order of 10(-4). We discuss whether different replication modes may confer an adaptive advantage to viruses.

FIG. 1.

Burst size of φ6 sus297 on permissive host S4. See the text for details.

FIG. 2.

Variance-to-mean ratios for the number of mutants expected for different values of m, where m is the probability per round of genome replication that a progeny virus becomes a replicative template. Bars represent the 95% confidence limits of the variance-to-mean ratios generated by the model (see the text for details). The dashed line denotes a ratio of 1.37, which was the value observed in our experiment. Only an m value of 10⁻⁴ generated 95% limits that contained the observed value of 1.37.