Noise effects the robustness of cells to environmental changes or results in phenotypes arising in monocloncal colonies. Here we study the effect of DNA replication---a process that is tightly controlled---on noise in mRNA levels. Stochastic simulations are used to study noise contributions from gene replication on constitutive and regulated gene expression and demonstrate that in order to capture mRNA distributions correctly, gene replication must be realistically modeled. Simulations show that slow relaxation of mRNA from the low steady-state prior to gene replication to the high steady-state after replication, the rate of which is set by mRNA half-life, contributes significantly to the noise and shape of mRNA distribution, and consequently both the intrinsic kinetics and the gene location play a role. Therefore any model or simulation that aims to capture the noise must account for the time-dependent relaxation of mRNA average and variance; in other words, interpretation experimental measurements of noise and kinetics in gene expression requires realistic simulation. Exact analytic equation for mRNA moments from constitutively expressed genes which are extended with approximate corrections for regulated expression, are presented that include kinetic, DNA copy number, gene location and cell doubling time dependences. These models and equations better capture the physics of the system than previous theories.

Time-dependent effects of DNA replication on mRNA noise

251st National Meeting (2016)

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