On the gain of entrainment in the $n$-dimensional ribosome flow model

TL;DR

This paper investigates how periodic modulation of transition rates in the n-dimensional ribosome flow model affects protein production, revealing conditions where constant rates are optimal and analyzing the gain of entrainment.

Contribution

It introduces a new approach to analyze the gain of entrainment in the general n-dimensional RFM, providing rigorous results and characterizing cases with no benefit from periodic rates.

Findings

In some cases, constant transition rates maximize protein production.

The paper characterizes scenarios where periodic rates do not improve production.

A new analytical method is developed for the n-dimensional RFM.

Abstract

The ribosome flow model (RFM) is a phenomenological model for the flow of particles along a 1D chain of $n$ sites. It has been extensively used to study ribosome flow along the mRNA molecule during translation. When the transition rates along the chain are time-varying and jointly $T$-periodic the RFM entrains, i.e., every trajectory of the RFM converges to a unique $T$-periodic solution that depends on the transition rates, but not on the initial condition. In general, entrainment to periodic excitations like the 24h solar day or the 50Hz frequency of the electric grid is important in numerous natural and artificial systems. An interesting question, called the gain of entrainment (GOE) in the RFM, is whether proper coordination of the periodic translation rates along the mRNA can lead to a larger average protein production rate. Analyzing the GOE in the RFM is non-trivial and partial results exist only for the RFM with dimensions $n=1,2$. We use a new approach to derive several results on the GOE in the general $n$-dimensional RFM. Perhaps surprisingly, we rigorously characterize several cases where there is no GOE, so to maximize the average production rate in these cases, the best choice is to use constant transition rates all along the chain.