Abstract

The Red Queen hypothesis posits that antagonistic co-evolution between interacting species results in recurrent natural selection via constant cycles of adaptation and counter-adaptation. Interactions such as these are at their most profound in host-parasite systems, with bacteria and their viruses providing the most intense of battlefields. Studies of bacteriophage evolution thus provide unparalleled insight into the remarkable elasticity of living entities. Here, we report a novel phenomenon underpinning the evolutionary trajectory of a group of dsDNA bacteriophages known as the phiKMVviruses. Employing deep next generation sequencing (NGS) analysis of nucleotide polymorphisms we discovered that this group of viruses generates enhanced intraspecies heterogeneity in their genomes. Our results show the localisation of variants to genes implicated in adsorption processes, as well as variation of the frequency and distribution of SNPs within and between members of the phiKMVviruses. We link error-prone DNA polymerase activity to the generation of variants. Critically, we show trans-activity of this phenomenon (the ability of a phiKMVvirus to dramatically increase genetic variability of a co-infecting phage), highlighting the potential of phages exhibiting such capabilities to influence the evolutionary path of other viruses on a global scale.

Highlights

  • Knowledge of evolutionary processes is one of the pillars of biology, and viruses have been paramount in our understanding of a number of such phenomena

  • The phiKMVviruses[13] are a group of ubiquitously distributed lytic dsDNA bacteriophages related to enterobacterial phage T7, some of which are utilised in a number of therapeutic preparations targeting the nosocomial pathogen Pseudomonas aeruginosa[13,14]

  • The study of the phiKMVvirus phiNFS, isolated from a Russian therapeutic phage preparation, revealed a broad host-range and unusual growth patterns. This included a cyclic interchange between phases of clear lysis along with regions of bacterial overgrowth indicative of pseudolysogeny (Fig. 1)

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Summary

Introduction

Knowledge of evolutionary processes is one of the pillars of biology, and viruses have been paramount in our understanding of a number of such phenomena. 11 of the 15 variants exist within the structural module of the phage genome, including 7 in the tail fibre protein (Figs 2b and 3), the major host tropism determinant[15].

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