Repeatability and Contingency in the Evolution of a Key Innovation in Phage Lambda

The processes responsible for the evolution of key innovations, whereby lineages acquire new functions that open novel ecological opportunities, have long been debated. Two central questions concern the evolutionary processes that drive the emergence of novelty and whether these transitions are repeatable. To address these questions we studied how a virus, bacteriophage ?, evolved to infect its host, Escherichia coli, through a novel pathway. We demonstrate that natural selection promoted the fixation of mutations that improved fitness on the original receptor, LamB, while also setting the stage for further mutations that allowed exploitation of a new receptor, OmpF. The novel function evolved in 24 of 96 phage populations, and in all cases required four mutations in the J protein. Replay experiments show that whether the necessary combination of mutations evolved was contingent on the coevolution of the host population. Mutations in the host’s malT gene promoted the evolution of the phage’s ability to exploit the OmpF receptor, whereas mutations in manY and manZ precluded the phage from evolving that function. This study illustrates the complex interplay between genomic processes and ecological conditions that favor the emergence of evolutionary innovations.