(A) Without positive selection plasmids are gradually lost from a population (squares containing individual cells (circles)) due to missegregation and slower growth of plasmid-carrying cells. Compensatory mutations reduce the cost of plasmid carriage, increasing its persistence, but missegregation will lead to eventual extinction in the absence of plasmid transmission. (B) This extinction will be hastened if adaptive mutations that increase cell fitness occur in the plasmid-free subpopulation, thereby increasing the relative fitness of plasmid-free to plasmid-carrying cells. (C) A pulse of positive selection for the plasmid resets its frequency in the population to one, increasing the chance that any new adaptive mutations occur in the plasmid-carrying subpopulation.