Stress-Induced Constraint on Expression Noise of Essential Genes in E. coli.

Gene expression is an inherently noisy process that is constrained by natural selection. Yet the condition dependence of constraint on expression noise remains unclear. Here, we address this problem by studying constraint on expression noise of E. coli genes in eight diverse growth conditions. In particular, we use variation in expression noise as an analog for constraint, examining its relationships to expression level and to the number of regulatory inputs from transcription factors across and within conditions. We show that variation in expression noise is negatively associated with expression level, implicating constraint to minimize expression noise of highly expressed genes. However, this relationship is condition dependent, with the strongest constraint observed when E. coli are grown in the presence of glycerol or ciprofloxacin, which result in carbon or antibiotic stress, respectively. In contrast, we do not observe evidence of constraint on expression noise of highly regulated genes, suggesting that highly expressed and highly regulated genes represent distinct classes of genes. Indeed, we find that essential genes are often highly expressed but not highly regulated, with elevated expression noise in glycerol and ciprofloxacin conditions. Thus, our findings support the hypothesis that selective constraint on expression noise is condition dependent in E. coli, illustrating how it may play a critical role in ensuring expression stability of essential genes in unstable environments.