TY - JOUR T1 - Noise propagation in an integrated model of bacterial gene expression and growth JF - bioRxiv DO - 10.1101/246165 SP - 246165 AU - Istvan T. Kleijn AU - Laurens H. J. Krah AU - Rutger Hermsen Y1 - 2018/01/01 UR - http://biorxiv.org/content/early/2018/01/10/246165.abstract N2 - In bacterial cells, gene expression, metabolism, and growth are highly interdependent and tightly coordinated. As a result, stochastic fluctuations in expression levels and instantaneous growth rate show intricate cross-correlations. These correlations are shaped by feedback loops, trade-offs and constraints acting at the cellular level; therefore a quantitative understanding requires an integrated approach. To that end, we here present a mathematical model describing a cell that contains multiple enzymes that are each expressed stochastically and jointly limit the growth rate. Conversely, metabolism and growth affect protein synthesis and dilution. Thus, expression noise originating in one gene propagates to metabolism, growth, and the expression of all other genes. Nevertheless, under a small-noise approximation many statistical quantities can be calculated analytically. We identify several routes of noise propagation, illustrate their origins and scaling, and establish important connections with metabolic control analysis. We then present a many-protein model parameterized by previously measured protein abundance data and demonstrate that the predicted cross-correlations between gene expression and growth rate are in broad agreement with published measurements. ER -