Abstract
Gene translation is a central stage in the intracellular process of protein synthesis. Gene translation proceeds in three major stages: initiation, elongation, and termination. During the elongation step, ribosomes (intracellular macromolecules) link amino acids together in the order specified by messenger RNA (mRNA) molecules. The homogeneous ribosome flow model (HRFM) is a mathematical model of translation-elongation under the assumption of constant elongation rate along the mRNA sequence. The HRFM includes $(n)$ first-order nonlinear ordinary differential equations, where $(n)$ represents the length of the mRNA sequence, and two positive parameters: ribosomal initiation rate and the (constant) elongation rate. Here, we analyze the HRFM when $(n)$ goes to infinity and derive a simple expression for the steady-state protein synthesis rate. We also derive bounds that show that the behavior of the HRFM for finite, and relatively small, values of $(n)$ is already in good agreement with the closed-form result in the infinite-dimensional case. For example, for $(n=15)$, the relative error is already less than 4 percent. Our results can, thus, be used in practice for analyzing the behavior of finite-dimensional HRFMs that model translation. To demonstrate this, we apply our approach to estimate the mean initiation rate in M. musculus, finding it to be around 0.17 codons per second.
| Original language | English |
|---|---|
| Article number | 6731359 |
| Pages (from-to) | 1322-1328 |
| Number of pages | 7 |
| Journal | IEEE/ACM Transactions on Computational Biology and Bioinformatics |
| Volume | 10 |
| Issue number | 5 |
| DOIs | |
| State | Published - Sep 2013 |
Keywords
- Gene translation
- computational models
- monotone dynamical systems
- periodic continued fractions
- systems biology
All Science Journal Classification (ASJC) codes
- Biotechnology
- Genetics
- Applied Mathematics
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