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Cell-cycle coupled expression minimizes random fluctuations in gene product levels

Mohammad Soltani, Abhyudai Singh
doi: https://doi.org/10.1101/052159
Mohammad Soltani
1.Department of Electrical and Computer Engineering, University of Delaware, Newark, DE, USA.
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Abhyudai Singh
1.Department of Electrical and Computer Engineering, University of Delaware, Newark, DE, USA.
2.Department of Mathematical Sciences, University of Delaware, Newark, DE, USA.
3.Department of Biomedical Engineering, University of Delaware, Newark, DE, USA.
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  • For correspondence: absingh@udel.edu
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Abstract

Expression of many genes varies as a cell transitions through different cell-cycle stages. How coupling between stochastic expression and cell cycle impacts cell-to-cell variability (noise) in the level of protein is not well understood. We analyze a model, where a stable protein is synthesized in random bursts, and the frequency with which bursts occur varies within the cell cycle. Formulas quantifying the extent of fluctuations in the protein copy number are derived and decomposed into components arising from the cell cycle and stochastic processes. The latter stochastic component represents contributions from bursty expression and errors incurred during partitioning of molecules between daughter cells. These formulas reveal an interesting trade-off: cell-cycle dependencies that amplify the noise contribution from bursty expression also attenuate the contribution from partitioning errors. We investigate existence of optimum strategies for coupling expression to the cell cycle that minimize the stochastic component. Intriguingly, results show that a zero production rate throughout the cell cycle, with expression only occurring just before cell division minimizes noise from bursty expression for a fixed mean protein level. In contrast, the optimal strategy in the case of partitioning errors is to make the protein just after cell division. We provide examples of regulatory proteins that are expressed only towards the end of cell cycle, and argue that such strategies enhance robustness of cell-cycle decisions to the intrinsic stochasticity of gene expression.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted May 08, 2016.
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Cell-cycle coupled expression minimizes random fluctuations in gene product levels
Mohammad Soltani, Abhyudai Singh
bioRxiv 052159; doi: https://doi.org/10.1101/052159
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Cell-cycle coupled expression minimizes random fluctuations in gene product levels
Mohammad Soltani, Abhyudai Singh
bioRxiv 052159; doi: https://doi.org/10.1101/052159

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