Power series method for solving TASEP-based models of mRNA translation

We develop a method for solving mathematical models of messenger RNA (mRNA) translation based on the totally asymmetric simple exclusion process (TASEP). Our main goal is to demonstrate that the method is versatile and applicable to realistic models of translation. To this end we consider the TASEP with codon-dependent elongation rates, premature termination due to ribosome drop-off and translation reinitiation due to circularisation of the mRNA. We apply the method to the model organism {\it Saccharomyces cerevisiae} under physiological conditions and find excellent agreements with the results of stochastic simulations. Our findings suggest that the common view on translation as being rate-limited by initiation is oversimplistic. Instead we find theoretical evidence for ribosome interference and also theoretical support for the ramp hypothesis which argues that codons at the beginning of genes have slower elongation rates in order to reduce ribosome density and jamming.Comment: 13 pages, 10 figure

Totally asymmetric exclusion process with long-range hopping

Generalization of the one-dimensional totally asymmetric exclusion process (TASEP) with open boundary conditions in which particles are allowed to jump $l$ sites ahead with the probability $p_l\sim 1/l^{\sigma+1}$ is studied by Monte Carlo simulations and the domain-wall approach. For $\sigma>1$ the standard TASEP phase diagram is recovered, but the density profiles near the transition lines display new features when $1<\sigma<2$. At the first-order transition line, the domain-wall is localized and phase separation is observed. In the maximum-current phase the profile has an algebraic decay with a $\sigma$-dependent exponent. Within the $\sigma \leq 1$ regime, where the transitions are found to be absent, analytical results in the continuum mean-field approximation are derived in the limit $\sigma=-1$.Comment: 10 pages, 9 figure

Absence of phase coexistence in disordered exclusion processes with bypassing

Adding quenched disorder to the one-dimensional asymmetric exclusion process is known to always induce phase separation. To test the robustness of this result, we introduce two modifications of the process that allow particles to bypass defect sites. In the first case, particles are allowed to jump l sites ahead with the probability p_l ~ l^-(1+sigma), where sigma>1. By using Monte Carlo simulations and the mean-field approach, we show that phase coexistence may be absent up to enormously large system sizes, e.g. lnL~50, but is present in the thermodynamic limit, as in the short-range case. In the second case, we consider the exclusion process on a quadratic lattice with symmetric and totally asymmetric hopping perpendicular to and along the direction of driving, respectively. We show that in an anisotropic limit of this model a regime may be found where phase coexistence is absent.Comment: 18 pages, 10 figures, to appear in JSTA

Conditioned random walks and interaction-driven condensation

We consider a discrete-time continuous-space random walk under the constraints that the number of returns to the origin (local time) and the total area under the walk are fixed. We first compute the joint probability of an excursion having area $a$ and returning to the origin for the first time after time $\tau$. We then show how condensation occurs when the total area constraint is increased: an excursion containing a finite fraction of the area emerges. Finally we show how the phenomena generalises previously studied cases of condensation induced by several constraints and how it is related to interaction-driven condensation which allows us to explain the phenomenon in the framework of large deviation theory.Comment: 28 pages, 6 figures, invited paper for Special Issue of J. Phys. A "Emerging talents

Inequivalence of nonequilibrium path ensembles: the example of stochastic bridges

We study stochastic processes in which the trajectories are constrained so that the process realises a large deviation of the unconstrained process. In particular we consider stochastic bridges and the question of inequivalence of path ensembles between the microcanonical ensemble, in which the end points of the trajectory are constrained, and the canonical or s ensemble in which a bias or tilt is introduced into the process. We show how ensemble inequivalence can be manifested by the phenomenon of temporal condensation in which the large deviation is realised in a vanishing fraction of the duration (for long durations). For diffusion processes we find that condensation happens whenever the process is subject to a confining potential, such as for the Ornstein-Uhlenbeck process, but not in the borderline case of dry friction in which there is partial ensemble equivalence. We also discuss continuous-space, discrete-time random walks for which in the case of a heavy tailed step-size distribution it is known that the large deviation may be achieved in a single step of the walk. Finally we consider possible effects of several constraints on the process and in particular give an alternative explanation of the interaction-driven condensation in terms of constrained Brownian excursions.Comment: 22 pages, 7 figures, minor revisio

Inherent Variability in the Kinetics of Autocatalytic Protein Self-Assembly

In small volumes, the kinetics of filamentous protein self-assembly is expected to show significant variability, arising from intrinsic molecular noise. This is not accounted for in existing deterministic models. We introduce a simple stochastic model including nucleation and autocatalytic growth via elongation and fragmentation, which allows us to predict the effects of molecular noise on the kinetics of autocatalytic self-assembly. We derive an analytic expression for the lag-time distribution, which agrees well with experimental results for the fibrillation of bovine insulin. Our expression decomposes the lag time variability into contributions from primary nucleation and autocatalytic growth and reveals how each of these scales with the key kinetic parameters. Our analysis shows that significant lag-time variability can arise from both primary nucleation and from autocatalytic growth, and should provide a way to extract mechanistic information on early-stage aggregation from small-volume experiments.Comment: 5pp, 3 fig. + Supp. Mat. (7pp, 4 fig.), accepted for publication in PR

Disordered exclusion process revisited:some exact results in the low-current regime

We study steady state of the totally asymmetric simple exclusion process with inhomogeneous hopping rates associated with sites (site-wise disorder). Using the fact that the non-normalized steady-state weights which solve the master equation are polynomials in all the hopping rates, we propose a general method for calculating their first few lowest coefficients exactly. In case of binary disorder where all slow sites share the same hopping rate r<1, we apply this method to calculate steady-state current up to the quadratic term in r for some particular disorder configurations. For the most general (non-binary) disorder, we show that in the low-current regime the current is determined solely by the current-minimizing subset of equal hopping rates, regardless of other hopping rates. Our approach can be readily applied to any other driven diffusive system with unidirectional hopping if one can identify a hopping rate such that the current vanishes when this rate is set to zero.Comment: 26 pages, 7 figures, iopart class, submitted to J. Phys.

Conditioned stochastic particle systems and integrable quantum spin systems

We consider from a microscopic perspective large deviation properties of several stochastic interacting particle systems, using their mapping to integrable quantum spin systems. A brief review of recent work is given and several new results are presented: (i) For the general disordered symmectric exclusion process (SEP) on some finite lattice conditioned on no jumps into some absorbing sublattice and with initial Bernoulli product measure with density $\rho$ we prove that the probability $S_\rho(t)$ of no absorption event up to microscopic time $t$ can be expressed in terms of the generating function for the particle number of a SEP with particle injection and empty initial lattice. Specifically, for the symmetric simple exclusion process on $\mathbb Z$ conditioned on no jumps into the origin we obtain the explicit first and second order expansion in $\rho$ of $S_\rho(t)$ and also to first order in $\rho$ the optimal microscopic density profile under this conditioning. For the disordered ASEP on the finite torus conditioned on a very large current we show that the effective dynamics that optimally realizes this rare event does not depend on the disorder, except for the time scale. For annihilating and coalescing random walkers we obtain the generating function of the number of annihilated particles up to time $t$, which turns out to exhibit some universal features.Comment: 25 page