title: Negative feedback and transcriptional overshooting in a regulatory network for horizontal gene transfer.
abstract: Horizontal gene transfer (HGT) is a major force driving bacterial evolution. Because of their ability to cross inter-species barriers, bacterial plasmids are essential agents for HGT. This ability, however, poses specific requisites on plasmid physiology, in particular the need to overcome a multilevel selection process with opposing demands. We analyzed the transcriptional network of plasmid R388, one of the most promiscuous plasmids in Proteobacteria. Transcriptional analysis by fluorescence expression profiling and quantitative PCR revealed a regulatory network controlled by six transcriptional repressors. The regulatory network relied on strong promoters, which were tightly repressed in negative feedback loops. Computational simulations and theoretical analysis indicated that this architecture would show a transcriptional burst after plasmid conjugation, linking the magnitude of the feedback gain with the intensity of the transcriptional burst. Experimental analysis showed that transcriptional overshooting occurred when the plasmid invaded a new population of susceptible cells. We propose that transcriptional overshooting allows genome rebooting after horizontal gene transfer, and might have an adaptive role in overcoming the opposing demands of multilevel selection.
authors.affiliation: Instituto de Biomedicina y Biotecnologia de Cantabria (IBBTEC), Santander, Spain.
authors.forename: Raul
authors.initials: R
authors.lastname: Fernandez-Lopez
authors.affiliation: Instituto de Biomedicina y Biotecnologia de Cantabria (IBBTEC), Santander, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Del Campo
authors.affiliation: Instituto de Biomedicina y Biotecnologia de Cantabria (IBBTEC), Santander, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Revilla
authors.affiliation: Instituto de Biomedicina y Biotecnologia de Cantabria (IBBTEC), Santander, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Cuevas
authors.affiliation: Instituto de Biomedicina y Biotecnologia de Cantabria (IBBTEC), Santander, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: de la Cruz
mesh_terms: D003198:Computer Simulation; D019143:Evolution, Molecular; D053263:Gene Regulatory Networks; D022761:Gene Transfer, Horizontal; D016680:Genome, Bacterial; D010957:Plasmids / Q000235:genetics*; D020560:Proteobacteria / Q000235:genetics*; D012641:Selection, Genetic / Q000235:genetics*