The central control operon of plasmid RK2 is an example of a natural system of negative and co-operative autoregulation. The available data for the operon regulation by dimers of two global regulators, KorA and KorB, are insufficient for full reconstruction of the system. Therefore, we aim to explore possible dynamics of the system and use Bayesian inference to estimate unknown parameters. Additionally, we would like to contribute to the scientific discussion about the roles of a negative loop in biosystems. We present possible reasons for optimization of the central control operon through comparative analyses of the wild type system with a progression of simpler systems.
Analyses of the RK2 central control operon regulation were carried out by considering the steady state of a deterministic model of the system during exponential host bacterial growth. Using the Metropolis-Hastings algorithm we have estimated protein synthesis rates and revealed insignificance of monomerization rates to the model. For evolutionary optimization analyses, we have built a stochastic multi-scale model, which includes operon regulation, plasmid replication and host cell growth and division. We have examined the architecture of the central control operon regulation and its simpler equivalents, in terms of noise, robustness, speed up in response time and burden for a host. Results have shown that possible evolutionary optimization of the central control operon might be speed up in response time and decrease in burden for a host, as indicated by a decrease in number of produced mRNA. Fluctuations and robustness do not seem to play a significant role in this case.
In summary, we have explored possible dynamics of the RK2 central control operon regulation using Bayesian framework and demonstrated possible reasons for evolution of the regulatory architecture of the naturally occuring negative and cooperative autoregulation.