Bacteria often respond to dynamically changing environments by regulating gene expression. Despite this regulation being critically important for growth and survival, little is known about how selection shapes gene regulation in natural populations. To better understand the role natural selection plays in shaping bacterial gene regulation, here we compare differences in the regulatory behaviour of naturally segregating promoter variants from Escherichia coli (which have been subject to natural selection) to randomly mutated promoter variants (which have never been exposed to natural selection). We quantify gene expression phenotypes (expression level, plasticity and noise) for hundreds of promoter variants across multiple environments and show that segregating promoter variants are enriched for mutations with minimal effects on expression level. In many promoters, we infer that there is strong selection to maintain high levels of plasticity, and direct selection to decrease or increase cell-to-cell variability in expression. Taken together, these results expand our knowledge of how gene regulation is affected by natural selection and highlight the power of comparing naturally segregating polymorphisms to de novo random mutations to quantify the action of selection.

细菌通常通过调节基因表达来响应动态变化的环境。尽管这种调节对生长和生存至关重要，但人们对选择如何塑造自然种群中的基因调节知之甚少。为了更好地理解自然选择在塑造细菌基因调控中所起的作用，我们在这里比较了从大肠杆菌中自然分离的启动子变体的调控行为的差异（经过自然选择）随机突变的启动子变体（从未经历过自然选择）。我们量化了多种环境中数百个启动子变体的基因表达表型（表达水平、可塑性和噪声），并表明分离的启动子变体富含突变，对表达水平的影响最小。在许多启动子中，我们推断存在强选择以保持高水平的可塑性，并直接选择以减少或增加细胞间表达的变异性。总之，这些结果扩展了我们对自然选择如何影响基因调控的知识，并突出了将自然分离的多态性与从头随机突变进行比较以量化选择作用的能力。