Simulating Genetic Circuits in Bacterial Populations with Growth Heterogeneity.

ABSTRACT

We computationally study genetic circuits in bacterial populations with heterogeneities in the growth rate. To that end, we present a stochastic simulation method for gene circuits in populations of cells and propose an efficient implementation that we call the "Next Family Method". Within this approach, we implement different population setups, specifically Chemostat-type growth and growth in an ideal Mother Machine and show that the population structure and its statistics are different for the different setups whenever there is growth heterogeneity. Such dependence on the population setup is demonstrated, in the case of bistable systems with different growth rates in the stable states, to have distinctive signatures on quantities including the distributions of protein concentration and growth rates, and hysteresis curves. Applying this method to a bistable antibiotic resistance circuit, we find that as a result of the different statistics in different population setups, the estimated minimal inhibitory concentration of the antibiotic becomes dependent on the population setup in which it is measured.