Dorota’s second paper has just been published in PLoS ONE as:
Herman, D., Thomas, C.M. and Stekel, D.J. 2012. Adaptation for Protein Synthesis Efficiency in a Naturally Occurring Self-Regulating Operon. PLoS ONE 7(11): e49678.
We are particularly pleased with this work, and had some very nice comments from the reviewers. The quotes (from two different reviewers) here are reproduced with permission from PLoS ONE:
“the kinds of questions the authors address appear to be the most rewarding uses of computational/mathematical uses in biology”
“I found this paper important because it investigates a system with biological plausible parameters, thus, revealing whether the results of previous purely theoretical studies are biologically plausible.”
We are hoping for that sort of reception more generally in the community!
The abstract of the paper is:
The korAB operon in RK2 plasmids is a beautiful natural example of a negatively and cooperatively self-regulating operon. It has been particularly well characterized both experimentally and with mathematical models. We have carried out a detailed investigation of the role of the regulatory mechanism using a biologically grounded mechanistic multi-scale stochastic model that includes plasmid gene regulation and replication in the context of host growth and cell division. We use the model to compare four hypotheses for the action of the regulatory mechanism: increased robustness to extrinsic factors, decreased protein fluctuations, faster response-time of the operon and reduced host burden through improved efficiency of protein production. We find that the strongest impact of all elements of the regulatory architecture is on improving the efficiency of protein synthesis by reduction in the number of mRNA molecules needed to be produced, leading to a greater than ten-fold reduction in host energy required to express these plasmid proteins. A smaller but still significant role is seen for speeding response times, but this is not materially improved by the cooperativity. The self-regulating mechanisms have the least impact on protein fluctuations and robustness. While reduction of host burden is evident in a plasmid context, negative self-regulation is a widely seen motif for chromosomal genes. We propose that an important evolutionary driver for negatively self-regulated genes is to improve the efficiency of protein synthesis.