Bimodality in E. coli gene expression: Sources and robustness to genome-wide stresses.

Bacteria evolved genes whose single-cell distributions of expression levels are broad, or even bimodal. Evidence suggests that they might enhance phenotypic diversity for coping with fluctuating environments. We identified seven genes in E. coli with bimodal (low and high) single-cell expression levels under standard growth conditions and studied how their dynamics are modified by environmental and antibiotic stresses known to target gene expression. We found that all genes lose bimodality under some, but not under all, stresses. Also, bimodality can reemerge upon cells returning to standard conditions, which suggests that the genes can switch often between high and low expression rates. As such, these genes could become valuable components of future multi-stable synthetic circuits. Next, we proposed models of bimodal transcription dynamics with realistic parameter values, able to mimic the outcome of the perturbations studied. We explored several models' tunability and boundaries of parameter values, beyond which it shifts to unimodal dynamics. From the model results, we predict that bimodality is robust, and yet tunable, not only by RNA and protein degradation rates, but also by the fraction of time that promoters remain unavailable for new transcription events. Finally, we show evidence that, although the empirical expression levels are influenced by many factors, the bimodality emerges during transcription initiation, at the promoter regions and, thus, may be evolvable and adaptable.