Experimental Evolution of Pathogenesis: “Patient” Research

Twenty-five years and over 50,000 bacterial generations ago, one of the longest open-ended experiments in modern times began when the Lenski laboratory started passaging Escherichia coli under conditions of limited glucose as a carbon source [1]. Later that same year, a paper was published describing a new method for DNA sequencing, called pyrosequencing, that would ultimately light a path toward massively parallel (next-generation) sequencing [2]. As of 2013, a raw megabase of DNA costs less than $0.10 [3], or roughly equivalent to the cost of one petri dish. Combined with access to this affordable, high-throughput sequencing, experimental evolution [4] represents a sophisticated approach to dissecting hostpathogen interactions and testing models of host range and pathogen adaptation. Here, we review how experimental evolution has been used to directly test models of host-pathogen interactions (Figure 1). We discuss parallels between these laboratory studies and the real-world evolutionary trajectories that have been uncovered through the direct sequencing of clinical isolates.