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Abstract

In response to dynamically changing growth conditions, bacteria often modify protein expression levels by altering transcription rates, translation rates, or both. These regulatory changes are clearly subject to natural selection. To investigate how selection forces affect transcriptional regulation, we implement an experimental system which allows sensitive measurement of transcriptional changes in isolation from translation. We contrast the transcriptional phenotypes of promoter variants currently segregating in natural populations of E. coli (which have been subject to natural selection) with random promoter variants that have never been subjected to natural selection. By quantifying differences in random vs. naturally occurring transcriptional phenotypes we can infer selective pressures. We assess selective forces shaping three transcriptional phenotypes of the E. coli lacZ promoter: transcriptional activity, plasticity (dynamic range), and cell-to-cell variability (noise). We demonstrate that natural selection has acted on lacZ transcriptional phenotypes: stabilizing selection has filtered out mutations causing large changes in transcription and directional selection has maximized transcriptional plasticity. We also find signatures of disruptive selection that has resulted in some naturally segregating promoters to exhibit high noise, while others exhibit low noise. The differences in noise levels seem to be mediated by only one or two strongly linked SNPs that have been maintained since the earliest divergence of E. coli subtypes. These results provide new insight into how one of the most well-characterized bacterial promoters is shaped by natural selection.