Analytic approaches to stochastic gene expression in multicellular systems.

Deterministic thermodynamic models of the complex systems, which control gene expression in metazoa, are helping researchers identify fundamental themes in the regulation of transcription. However, quantitative single cell studies are increasingly identifying regulatory mechanisms that control variability in expression. Such behaviors cannot be captured by deterministic models and are poorly suited to contemporary stochastic approaches that rely on continuum approximations, such as Langevin methods. Fortunately, theoretical advances in the modeling of transcription have assembled some general results that can be readily applied to systems being explored only through a deterministic approach. Here, I review some of the recent experimental evidence for the importance of genetically regulating stochastic effects during embryonic development and discuss key results from Markov theory that can be used to model this regulation. I then discuss several pairs of regulatory mechanisms recently investigated through a Markov approach. In each case, a deterministic treatment predicts no difference between the mechanisms, but the statistical treatment reveals the potential for substantially different distributions of transcriptional activity. In this light, features of gene regulation that seemed needlessly complex evolutionary baggage may be appreciated for their key contributions to reliability and precision of gene expression.