Bacteriophage lambda overcomes a perturbation in its host-viral genetic network through mutualism and evolution of life history traits.

An important driver of evolution in viruses is natural selection to optimize the use of their hosts' genetic network. To learn how viruses respond to this pressure, we disrupted the genetic network of Escherichia coli to inhibit replication of its virus, bacteriophage lambda, and then observed how λ evolved to compensate. We deleted E. coli's dnaJ gene, which lambda uses to initiate DNA replication. Lambda partially restored its ability to reproduce with just two adaptive mutations associated with genes J and S. The location of the mutations was unexpected because they were not in genes that directly interact with DnaJ, rather they affected seemingly unrelated life history traits. A nonsynonymous J mutation increased lambda's adsorption rate and an S regulatory mutation delayed lysis timing. Lambda also recovered some of its reproductive potential through intracellular mutualism. This study offers two important lessons: first, viruses can rapidly adapt to disruptive changes in their host's genetic network. Second, organisms can employ mechanisms thought to operate at the population scale, such as evolution of life history traits and social interactions, in order to overcome hurdles at the molecular level. As life science research progresses and new fields become increasingly specialized, these results remind us of the importance of multiscale and interdisciplinary approaches to understand adaptation.