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Dynamical predictors of an imminent phenotypic switch in bacteria

Huijing Wang, View ORCID ProfileJ. Christian J. Ray
doi: https://doi.org/10.1101/145821
Huijing Wang
1Center for Computational Biology, University of Kansas, Lawrence, KS, USA
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J. Christian J. Ray
1Center for Computational Biology, University of Kansas, Lawrence, KS, USA
2Department of Molecular Biosciences University of Kansas, Lawrence, KS, USA
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  • ORCID record for J. Christian J. Ray
  • For correspondence: jjray@ku.edu
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Abstract

Single cells can stochastically switch across thresholds imposed by regulatory networks. Such thresholds can act as a tipping point, drastically changing global phenotypic states. In ecology and economics, imminent transitions across such tipping points can be predicted using dynamical early warning indicators. A typical example is "flickering" of a fast variable, predicting a longer-lasting switch from a low to a high state or vice versa. Considering the different timescales between metabolite and protein fluctuations in bacteria, we hypothesized that metabolic early warning indicators predict imminent transitions across a network threshold caused by enzyme saturation. We used stochastic simulations to determine if flickering predicts phenotypic transitions, accounting for a variety of molecular physiological parameters, including enzyme affinity, burstiness of enzyme gene expression, homeostatic feedback, and rates of metabolic precursor influx. In most cases, we found that metabolic flickering rates are robustly peaked near the enzyme saturation threshold. The degree of fluctuation was amplified by product inhibition of the enzyme. We conclude that sensitivity to flickering in fast variables may be a possible natural or synthetic strategy to prepare physiological states for an imminent transition.

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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-NC 4.0 International license.
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Posted June 03, 2017.
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Dynamical predictors of an imminent phenotypic switch in bacteria
Huijing Wang, J. Christian J. Ray
bioRxiv 145821; doi: https://doi.org/10.1101/145821
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Dynamical predictors of an imminent phenotypic switch in bacteria
Huijing Wang, J. Christian J. Ray
bioRxiv 145821; doi: https://doi.org/10.1101/145821

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