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Delay-induced stochastic oscillations in gene regulation.
Dmitri Bratsun1, Dmitri Volfson, Lev S Tsimring
1Department of Bioengineering, University of California at San Diego, La Jolla, CA 92093, USA.
Summary
Time delays in gene expression can induce oscillations and instability, even in systems without them. This delay-induced instability can impair negative feedback loops, impacting gene regulation and cellular function.
Area of Science:
- Biochemistry
- Systems Biology
- Computational Biology
Background:
- Gene regulation involves few molecules, causing significant fluctuations (noise) in mRNA and protein levels.
- Previous studies on stochastic gene expression primarily focused on instantaneous events, neglecting the impact of time delays.
Purpose of the Study:
- To investigate the combined effects of time delay and intrinsic noise on gene regulation.
- To analyze how delays influence the stability and oscillatory behavior of gene regulatory networks.
Main Methods:
- Developed a generalized Gillespie algorithm to simulate biochemical reactions with delays, accounting for non-Markovian properties.
- Derived analytical expressions for the correlation function and power spectrum of delayed stochastic gene expression.
- Compared simulation results with analytical findings.
Main Results:
- Time delays can induce oscillatory behavior in gene expression systems that are non-oscillatory under deterministic conditions.
- Delay-induced instabilities can significantly reduce the effectiveness of negative feedback loops in mitigating noise.
- The study provides a theoretical framework and computational tools for analyzing delayed stochastic processes in gene expression.
Conclusions:
- Time delays are a critical factor in understanding stochastic gene expression and its regulatory consequences.
- Delay-induced instabilities have implications for gene expression variability at the whole-genome scale, particularly in systems with negative feedback.