Modeling the Differential Fitness of Cyanobacterial Strains whose Circadian Oscillators have Different Free-running Periods: Comparing the Mutual Inhibition and Substrate Depletion Hypotheses

In a recent experimental study, Ouyang et al. (1998, Proc. Math. Acad. Sci. U.S.A.95, 8660–8664) have shown that, in direct competition, cyanobacterial strains whose circadian clocks have free-running periods (FRPs) which match the period of an imposed light/dark (LD) cycle exclude strains whose FRPs are out of resonance with the LD cycle. These differences in competitive fitness are observed despite the lack of measurable differences in monoculture growth rates between the strains. Here we show that the experimental results are consistent with a mathematical model in which cells rhythmically produce a metabolic inhibitor to which they display a sensitivity modulated by their circadian rhythm. We argue that models in which there is a circadian modulation of nutrient uptake kinetics cannot account for the results of these experiments. We discuss possible experiments to further characterize this phenomenon. The experimental protocol we propose can be used to distinguish between mutual inhibition and substrate depletion as underlying causes of the competitive advantage of circadian resonance.