UC San Diego

In order to carry out successful infections, bacteriophage lambda depends on many proteins in its host, the bacterium Escherichia coli. lambda proteins and lambda DNA interact with host molecules to facilitate infection and replication. These interactions form a molecular network known as the interactome. Viral evolution is therefore largely governed by changes that optimize the productivity of the interactome. Here, I present studies where we perturbed lambda’s interactome and allowed it to regain functionality through adaptive evolution. These studies provide insight into how viruses adapt, and more generally, how gene networks evolve. Previous studies have identified host genes used by lambda during infection. We used this knowledge in order to perturb the interactome by culturing lambda on a variety of host strains with one of these genes deleted. We proceeded to study lambda evolution to the 16 KOs and a wild type control to distinguish between specialized adaptations to specific KOs, or general adaptations to suboptimal laboratory conditions. Overall, most perturbations to the interactome could be solved with generic mutations that improve lambda growth, although, there are a few host gene deletions that require specialized mutations. Our study shows that viruses can easily adapt to perturbations in their interactomes through different adaptive solutions. While mutations with general benefits aid the correction of node deletions by providing disproportionate benefits for especially destructive deletions, some host gene deletions require specialized mutations.