Noise propagation in an integrated model of bacterial gene expression and growth

Istvan T. Kleijn, Laurens H. J. Krah, Rutger Hermsen, Alexandre V. Morozov
2018 PLoS Computational Biology  
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
more » ... that contains multiple proteins 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 between noise propagation and the field of metabolic control analysis. We then present a many-protein model containing >1000 proteins parameterized by previously measured abundance data and demonstrate that the predicted cross-correlations between gene expression and growth rate are in broad agreement with published measurements. Data Availability Statement: The expression data of Taniguchi et al [51] and Arike et al [53], used to parameterize the models of Fig 4 and S3 Fig., were published as supplementary datasets with the respective publications and can be accessed as such. The cross-correlation dataset of Kiviet et al [5], replotted in the top panels of Fig 4D-4F and S3 Fig. B-D, is available upon request from the corresponding author of that article (tans@amolf. nl). Funding: LHJK was supported by the NWO (Nederlandse Organisatie voor Wetenschappelijk measured protein abundances and show that it can reproduce the main features of measured cross-correlation functions between gene expression levels and growth rate. Noise propagation in bacterial gene expression and growth PLOS Computational Biology | https://doi.org/10.
doi:10.1371/journal.pcbi.1006386 fatcat:jlglbvbywzcefmgxi3ayfbnk2m