Coevolution of multiple growth traits in microbial populations under serial dilution

The relative fitness of mutants in a microbial population depends on multiple cellular traits. In the most widely-used evolution experiment protocol, serial dilution (where cells grow, enter stationary phase, and are diluted into a fresh medium), three major traits determining fitness are the growth rate, lag time (the duration of time cells do not grow when exiting stationary phase), and yield (number of cells per unit resource). Here we investigate how these traits coevolve in laboratory evolution experiments using a minimal model of population dynamics, where the only interaction between cells is competition for a single resource. We find that the fixation probability of a beneficial mutation depends on a linear combination of its growth rate and lag time relative to the background strain. The relative selective pressure on growth rate and lag time is set by the dilution factor; for example, a larger dilution factor favors adaptation of growth rate over the adaption of lag time. This result applies equally to the regime of large populations and high mutation rate, where there is abundant clonal interference, as well as the regime of sequential mutations. Moreover, we find an emergent correlation between growth rate and lag time even if mutations have uncorrelated effects.