Dynamics of a genetic toggle switch at the nucleotide and codon levels

Area of Science:

• Systems Biology
• Molecular Biology
• Biophysics

Background:

• Stochastic gene expression dynamics are crucial for cellular decision-making.
• Understanding gene regulatory network stability requires detailed modeling of molecular processes.

Purpose of the Study:

• To investigate the dynamics of a stochastic two-gene switch at nucleotide and codon levels.
• To determine how gene coupling affects information propagation and switch stability.
• To explore the impact of sequence-level events on gene circuit dynamics.

Main Methods:

• Developed a detailed stochastic model of a two-gene switch.
• Analyzed stability by comparing detailed models with simplified delayed models.
• Quantified gene coupling effects using mutual information between protein time series.
• Investigated the influence of transcription initiation, RNA degradation, and sequence-dependent transcription pauses.

Main Results:

• Detailed models are necessary for accurate switch dynamics, differing from simplified models.
• A specific gene coupling level maximizes information propagation between genes.
• Increased translation initiation rate enhances RNA-protein and inter-protein correlations.
• Transcription rate and RNA degradation influence correlations and stability differently.
• Sequence-dependent transcription pauses significantly impact switch dynamics.

Conclusions:

• Gene circuit dynamics are sensitive to detailed molecular processes and sequence-level features.
• Optimal gene coupling balances information transfer and system stability.
• Stochasticity and molecular details are essential for understanding gene switch behavior.