Transcription of bacterial genes is controlled by the coordinated action of cis- and trans-acting regulators. The activity and mode of action of these regulators can reflect different requirements for gene products in different environments. A well-studied example is the regulatory function that integrates the environmental availability of glucose and lactose to control the Escherichia coli lac operon. Most studies of lac operon regulation have focused on a few closely related strains. To determine the range of natural variation in lac regulatory function, we introduced a reporter construct into 23 diverse E. coli strains and measured expression with combinations of inducer concentrations. We found a wide range of regulatory functions. Several functions were similar to the one observed in a reference lab strain, whereas others depended weakly on the presence of cAMP. Some characteristics of the regulatory function were explained by the genetic relatedness of strains, indicating that differences varied on relatively short time scales. The regulatory characteristics explained by genetic relatedness were among those that best predicted the initial growth of strains following transition to a lactose environment, suggesting a role for selection. Finally, we transferred the lac operon, with the lacI regulatory gene, from five natural isolate strains into a reference lab strain. The regulatory function of these hybrid strains revealed the effect of local and global regulatory elements in controlling expression. Together, this work demonstrates that regulatory functions can be varied within a species and that there is variation within a species to best match a function to particular environments.IMPORTANCE The lac operon of Escherichia coli is a classic model for studying gene regulation. This study has uncovered features such as the environmental input logic controlling gene expression, as well as gene expression bistability and hysteresis. Most lac operon studies have focused on a few lab strains, and it is not known how generally those findings apply to the diversity of E. coli strains. We examined the environmental dependence of lac gene regulation in 20 natural isolates of E. coli and found a wide range of regulatory responses. By transferring lac genes from natural isolate strains into a common reference strain, we found that regulation depends on both the lac genes themselves and on the broader genetic background, indicating potential for still-greater regulatory diversity following horizontal gene transfer. Our results reveal that there is substantial natural variation in the regulation of the lac operon and indicate that this variation can be ecologically meaningful.

中文翻译：

---

多种大肠杆菌分离物中lac操纵子调控的多样性取决于更广泛的遗传背景，但遗传相关性无法解释。

细菌基因的转录受顺式和反式调节剂的协同作用控制。这些调节剂的活性和作用方式可以反映在不同环境中对基因产物的不同要求。一个经过充分研究的例子是调节功能，该功能整合了葡萄糖和乳糖在环境中的可利用性，以控制大肠杆菌的lac操纵子。lac操纵子调控的大多数研究都集中在一些密切相关的菌株上。为了确定lac调节功能的自然变异范围，我们将报告基因构建体引入了23种不同的大肠杆菌菌株中，并结合诱导剂浓度测量了表达。我们发现了各种各样的监管功能。几种功能类似于参考实验室菌株中观察到的功能，而其他人则很少依赖cAMP的存在。菌株的遗传相关性解释了调节功能的某些特征，表明差异在相对较短的时间尺度上变化。由遗传相关性解释的调节特性是最能预测菌株转变为乳糖环境后菌株初始生长的那些，提示了选择的作用。最后，我们将具有lacI调控基因的lac操纵子从五种天然分离株转移到参考实验室菌株中。这些杂种菌株的调控功能揭示了局部和全局调控元件在控制表达中的作用。一起，这项工作表明，调节功能可以在一个物种内变化，并且一个物种内存在变化，以使功能与特定环境最佳匹配。重要信息大肠杆菌的lac操纵子是研究基因调节的经典模型。这项研究发现了诸如控制基因表达的环境输入逻辑以及基因表达的双稳性和滞后性等特征。大多数紫胶操纵子研究都集中在少数实验室菌株上，尚不清楚这些发现在多大程度上适用于大肠杆菌菌株的多样性。我们检查了大肠杆菌中20种自然分离株中lac基因调控的环境依赖性，发现了广泛的调控反应。通过将lac基因从天然分离株中转移到共同的参考菌株中，我们发现调控既取决于lac基因本身，也取决于更广泛的遗传背景，表明水平基因转移后潜在的更大调控多样性。我们的研究结果表明，紫胶操纵子的调节存在很大的自然变化，并表明这种变化具有生态学意义。