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Asymmetric stochastic switching driven by intrinsic molecular noise
David Frigola1, Laura Casanellas, José M Sancho
1Department of Estructura i Constituents de la Matèria, Facultat de Fsica, Universitat de Barcelona, Barcelona, Spain.
Intrinsic fluctuations in low-copy-number molecules drive asymmetric switching in autoactivation genetic circuits. These fluctuations are fundamental to understanding stochastic switching and the relative stability of cellular states.
Area of Science:
- Systems Biology
- Molecular Systems Biology
- Biophysics
Background:
- Low-copy-number molecules are crucial for cellular functions, influencing cell behavior through inherent fluctuations.
- These molecular fluctuations can lead to stochastic switching between different cellular states, resulting in phenotypic variability.
- Understanding the dynamics of these states is essential for comprehending cellular decision-making.
Purpose of the Study:
- To theoretically and computationally investigate stochastic switching in a genetic autoactivation circuit.
- To elucidate the role of intrinsic fluctuations, arising from low molecule numbers, in driving this switching behavior.
- To compare theoretical predictions with experimental data from biological systems.
Main Methods:
- Theoretical modeling using Master Equations.
- Computational analysis employing Fokker-Planck and Langevin descriptions.
- Application to a genetic circuit featuring autoactivation.
Main Results:
- Intrinsic fluctuations in low-copy-number systems lead to state-dependent and asymmetric stochastic switching.
- The study demonstrates consistency between theoretical findings and experimental data from yeast's galactose signaling network.
- Intrinsic fluctuations are shown to be critical for understanding stochastic switching dynamics, not just for describing bistability.
Conclusions:
- Intrinsic fluctuations are fundamental drivers of stochastic switching in genetic circuits with low molecule counts.
- These fluctuations dictate the asymmetric nature and dynamics of switching between cellular states.
- The findings underscore the importance of considering molecular noise for a complete understanding of cellular phenotypes and state stability.
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