Transcriptional control of the lacZ promoter is under directional and diversifying selection

Bacterial cells often respond to changes in the environment by modifying protein expression. This can be achieved through changes in transcriptional or translational activity, or both. Recent research has shed some light on how natural selection shapes overall protein expression. Still, little is known about how selection acts on transcription or translation individually. To address part of this question, we implement an experimental system which allows us to measure how genetic changes affect transcription only, excluding the effects on translation. We use this system to quantify changes in three regulatory phenotypes of the lacZ promoter: transcriptional activity, plasticity, and cell-to-cell variability. We compare these phenotypes from segregating variants that have been subject to natural selection, and random variants that have never been subjected to natural selection. We show that natural selection filters out mutations causing large changes in transcriptional levels from the lacZ promoter. Further, we detect directional selection acting on transcriptional plasticity in combinations of glucose, galactose and lactose environments. Focusing on cell-to-cell variability in transcription, we describe both directional and diversifying selection acting on this phenotype depending on the environment used. We also observe a link between the phylogeny of the environmental E. coli strains and high and low transcriptional noise levels in glucose which are mediated by just one or two SNPs. Our results thus provide new insight into how one of the most well-characterized bacterial promoters is shaped in nature by selection. ### Competing Interest Statement The authors have declared no competing interest.