Search

Models intended to describe the time evolution of a gene network must somehow include transcription, the DNA-templated synthesis of RNA, and translation, the RNA-templated synthesis of proteins. In eukaryotes, the DNA template for transcription can be very long, often consisting of tens of thousands of nucleotides, and lengthy pauses may punctuate this process. Accordingly, transcription can last for many minutes, in some cases hours. There is a long history of introducing delays in gene expression models to take the transcription and translation times into account. Here we study a family of detailed transcription models that includes initiation, elongation, and termination reactions. We establish a framework for computing the distribution of transcription times, and work out these distributions for some typical cases. For elongation, a fixed delay is a good model provided elongation is fast compared to initiation and termination, and there are no sites where long pauses occur. The initiation and termination phases of the model then generate a nontrivial delay distribution, and elongation shifts this distribution by an amount corresponding to the elongation delay. When initiation and termination are relatively fast, the distribution of elongation times can be approximated by a Gaussian. A convolution of this Gaussian with the initiation and termination time distributions gives another analytic approximation to the transcription time distribution. If there are long pauses during elongation, because of the modularity of the family of models considered, the elongation phase can be partitioned into reactions generating a simple delay (elongation through regions where there are no long pauses), and reactions whose distribution of waiting times must be considered explicitly (initiation, termination, and motion through regions where long pauses are likely). In these cases, the distribution of transcription times again involves a nontrivial part and a shift due to fast elongation processes.

The conditions for the validity of the standard quasi-steady-state approximation in the Michaelis–Menten mechanism in a closed reaction vessel have been well studied, but much less so the conditions for the validity of this approximation for the system with substrate inflow. We analyze quasi-steady-state scenarios for the open system attributable to singular perturbations, as well as less restrictive conditions. For both settings we obtain distinguished invariant manifolds and time scale estimates, and we highlight the special role of singular perturbation parameters in higher order approximations of slow manifolds. We close the paper with a discussion of distinguished invariant manifolds in the global phase portrait.