title: Genomic location of the major ribosomal protein gene locus determines Vibrio cholerae global growth and infectivity.
abstract: The effects on cell physiology of gene order within the bacterial chromosome are poorly understood. In silico approaches have shown that genes involved in transcription and translation processes, in particular ribosomal protein (RP) genes, localize near the replication origin (oriC) in fast-growing bacteria suggesting that such a positional bias is an evolutionarily conserved growth-optimization strategy. Such genomic localization could either provide a higher dosage of these genes during fast growth or facilitate the assembly of ribosomes and transcription foci by keeping physically close the many components of these macromolecular machines. To explore this, we used novel recombineering tools to create a set of Vibrio cholerae strains in which S10-spec-α (S10), a locus bearing half of the ribosomal protein genes, was systematically relocated to alternative genomic positions. We show that the relative distance of S10 to the origin of replication tightly correlated with a reduction of S10 dosage, mRNA abundance and growth rate within these otherwise isogenic strains. Furthermore, this was accompanied by a significant reduction in the host-invasion capacity in Drosophila melanogaster. Both phenotypes were rescued in strains bearing two S10 copies highly distal to oriC, demonstrating that replication-dependent gene dosage reduction is the main mechanism behind these alterations. Hence, S10 positioning connects genome structure to cell physiology in Vibrio cholerae. Our results show experimentally for the first time that genomic positioning of genes involved in the flux of genetic information conditions global growth control and hence bacterial physiology and potentially its evolution.
authors: Institut Pasteur, Unité Plasticité du Génome Bactérien, Département Génomes et Génétique, Paris, France; Centre National de la Recherche Scientifique UMR3525, Paris, France.
authors: Alfonso
authors: A
authors: Soler-Bistué
authors: Institut Pasteur, Viruses and RNA Interference; Centre National de la Recherche Scientifique UMR3569, Paris, France.
authors: Juan A
authors: JA
authors: Mondotte
authors: Institut Pasteur, Unité Plasticité du Génome Bactérien, Département Génomes et Génétique, Paris, France; Centre National de la Recherche Scientifique UMR3525, Paris, France.
authors: Michael Jason
authors: MJ
authors: Bland
authors: Institut Pasteur, Unité Plasticité du Génome Bactérien, Département Génomes et Génétique, Paris, France; Centre National de la Recherche Scientifique UMR3525, Paris, France.
authors: Marie-Eve
authors: ME
authors: Val
authors: Institut Pasteur, Viruses and RNA Interference; Centre National de la Recherche Scientifique UMR3569, Paris, France.
authors: María-Carla
authors: MC
authors: Saleh
authors: Institut Pasteur, Unité Plasticité du Génome Bactérien, Département Génomes et Génétique, Paris, France; Centre National de la Recherche Scientifique UMR3525, Paris, France.
authors: Didier
authors: D
authors: Mazel
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000382:microbiology; D018628:Gene Dosage; D023061:Gene Order; D056426:Genetic Loci; D016680:Genome, Bacterial; D012269:Ribosomal Proteins / Q000235:genetics*; D014734:Vibrio cholerae / Q000235:genetics / Q000472:pathogenicity*; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D012269:Ribosomal Proteins