Noise and low-level dynamics can coordinate multicomponent bet hedging mechanisms

Area of Science:

• Cellular biology
• Systems biology
• Biophysics

Background:

• Cells employ stochastic gene expression for stress response, diversifying populations to hedge against environmental uncertainty.
• Coordinated expression of multiple genes is crucial for survival, posing a challenge for orchestrating rare events across many targets without incurring high costs.

Purpose of the Study:

• To investigate how cells coordinate the timing of multiple rare gene expression events without additional cost.
• To explore the role of transcription factor dynamics and noise in regulating downstream stress response genes.

Main Methods:

• Utilized a stochastic model to simulate transcription factor regulation of downstream target genes.
• Compared different upstream regulator profiles: constant expression, pulsatile dynamics, and noisy expression.
• Simulated the dynamics of the multiple antibiotic resistance activator (MarA) and 40 downstream genes.

Main Results:

• Pulsatile dynamics and noise in transcription factors are sufficient to coordinate the expression of multiple downstream genes.
• Coordination occurs even when upstream regulator fluctuations are below gene dissociation constants.
• Low-level dynamics in MarA effectively coordinated resistance gene expression, with noise playing a similar role.
• These coordinating benefits were achieved without increasing population-level costs.

Conclusions:

• Stochastic dynamics, specifically pulsatile or noisy expression of transcription factors, can coordinate multiple stress response genes.
• This coordination mechanism is efficient, engaging multiple genes simultaneously without imposing a higher cost on the cell population.
• The findings suggest a cost-effective strategy for cellular adaptation to unpredictable environmental challenges.