Figure 1. Stochastic tuning of gene expression by fitness optimization at gene promoters.

(A) Each gene contains a noisy expression apparatus with noise amplitude η that allows exploration of a range of transcriptional activities. Each transcription apparatus also maintains a record of its previous change in transcriptional activity (∆E_t-1). The change in transcriptional activity has the potential to contribute to a change in global health (∆F_t) through the downstream effect of the gene product’s activity (likely through a multi-step pathway; for example, the biosynthesis of a metabolite that is limiting for growth). A global metabolic integrator can transduce this change in health/fitness to every gene’s expression apparatus. At any point in time, the expression apparatus executes a change in transcriptional activity (∆E_t) proportional (k) to the sign (sgn) of the product of ∆E_t-1 and ∆F_t plus noise (η). (B) A simple example of this can be seen for a gene that experiences a random burst in transcriptional activity. If this leads to an increase in fitness the expression apparatus further increases transcriptional activity. Conversely, if there is a decrease in fitness, the expression apparatus decreases transcriptional activity.