While horizontal gene transfer is prevalent across the biosphere, the regulatory features that enable expression and functionalization of foreign DNA remain poorly understood. Here, we combine high-throughput promoter activity measurements and large-scale genomic analysis of regulatory regions to investigate the cross-compatibility of regulatory elements (REs) in bacteria. Functional characterization of thousands of natural REs in three distinct bacterial species revealed distinct expression patterns according to RE and recipient phylogeny. Host capacity to activate foreign promoters was proportional to their genomic GC content, while many low GC regulatory elements were both broadly active and had more transcription start sites across hosts. The difference in expression capabilities could be explained by the influence of the host GC content on the stringency of the AT-rich canonical σ70 motif necessary for transcription initiation. We further confirm the generalizability of this model and find widespread GC content adaptation of the σ70 motif in a set of 1,545 genomes from all major bacterial phyla. Our analysis identifies a key mechanism by which the strength of the AT-rich σ70 motif relative to a host’s genomic GC content governs the capacity for expression of acquired DNA. These findings shed light on regulatory adaptation in the context of evolving genomic composition.

虽然水平基因转移在整个生物圈中很普遍，但是使外源DNA的表达和功能化的调控功能仍然知之甚少。在这里，我们结合了高通量启动子活性测量和调控区域的大规模基因组分析，以研究细菌中调控元件（RE）的交叉兼容性。三种不同细菌物种中成千上万个天然RE的功能表征揭示了根据RE和受体系统发育的不同表达模式。宿主激活外源启动子的能力与它们的基因组GC含量成正比，而许多低GC调控元件既具有广泛的活性，又在宿主之间具有更多的转录起始位点。表达能力的差异可以通过宿主GC含量对转录起始所需的富含AT的规范化σ70基序的严格性的影响来解释。我们进一步证实了该模型的一般性，并在来自所有主要细菌门的1,545个基因组中发现了σ70基序的广泛的GC含量适应性。我们的分析确定了一个关键机制，通过该机制，富含AT的σ70基序相对于宿主基因组GC含量的强度决定了获得的DNA表达的能力。这些发现为基因组组成不断变化的背景下的调节适应提供了启示。所有主要细菌门的545个基因组。我们的分析确定了一个关键机制，通过该机制，富含AT的σ70基序相对于宿主基因组GC含量的强度决定了获得的DNA表达的能力。这些发现为基因组组成不断变化的背景下的调节适应提供了启示。所有主要细菌门的545个基因组。我们的分析确定了一个关键机制，通过该机制，富含AT的σ70基序相对于宿主基因组GC含量的强度决定了获得的DNA表达的能力。这些发现为基因组组成不断变化的背景下的调节适应提供了启示。