Effects of macromolecular transport and stochastic fluctuations on dynamics of genetic regulatory systems.

To predict the dynamics of genetic regulation, it may be necessary to consider macromolecular transport and stochastic fluctuations in macromolecule numbers. Transport can be diffusive or active, and in some cases a time delay might suffice to model active transport. We characterize major differences in the dynamics of model genetic systems when diffusive transport of mRNA and protein was compared with transport modeled as a time delay. Delays allow for history-dependent, non-Markovian responses to stimuli (i.e., "molecular memory"). Diffusion suppresses oscillations, whereas delays tend to create oscillations. When simulating essential elements of circadian oscillators, we found the delay between transcription and translation necessary for oscillations. Stochastic fluctuations tend to destabilize and thereby mask steady states with few molecules. This computational approach, combined with experiments, should provide a fruitful conceptual framework for investigating the function and dynamic properties of genetic regulatory systems.