Abstract
The origins of adaptive functions remain poorly understood, despite considerable interest (1-5) . Here, we report the de novo evolution of population-level feedback control in clonal Escherichia coli strains containing high-copy plasmids, enabling these strains to express green fluorescent protein (GFP) in response to tetracycline. Selection maintains tetA (+) and tetA (-) plasmids within single cells, due to negative feedback from the toxic effects of a tetA-gfp tetracycline resistance transposon. At high plasmid copy numbers, the intracellular equilibrium of tetA (+) and tetA (-) plasmids robustly responds to tetracycline through rapid evolutionary dynamics (6-8) . Theory predicts that the GFP response to tetracycline is determined by the covariance between GFP expression and bacterial fitness. Our findings show that small mutational changes can result in large qualitative changes to population-level behavior. Here, the evolution of polymorphic intracellular populations of mobile genetic elements allows host populations to dynamically respond to antibiotic in the environment.