Co-evolution of a filamentous bacteriophage and its defective interfering particles

Abstract

Serial passage of bacteriophage f1 at high multiplicities of infection results in the appearance of defective deletion mutants (miniphage) that harbor a tandem reiteration of regions of the f1 genome near the origin of DNA replication. These miniphage interfere with the growth of wild-type f1, and cause a sharp decrease of the viable phage titer. Upon further passage, however, the titer increases again. Viable phage variants (maxiphage) appear which harbor the same tandem reiteration of DNA as the miniphage. The maxiphage are more resistant than the wild type to interference by the miniphage. In the absence of miniphage the maxiphage grow at the same rate as the wild type. The structure of the DNA reiteration gradually changes during further passage. Miniphage and maxiphage follow, in parallel, a similar course of changes in the pattern of reiteration. In miniphage the reiterations change while the deletions are conserved. Serial passage of maxiphage quickly yields miniphage, which harbor a reiteration identical to that of the parental maxiphage. Both reiteration and deletion are relevant to the mechanism of interference by miniphage. Thus serial passage of the filamentous phage affords an experimental system to study evolution of a DNA genome in test tubes. Possible mechanisms of the interference by miniphage are discussed.