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1. Intracellular Positioning Systems Limit the Entropic Eviction of Secondary Replicons Toward the Nucleoid Edges in Bacterial Cells

Author

Dauverd -Girault, Julie, Planchenault, Charlène, Pons, Marine, Schiavon, Caroline, Siguier, Patricia, Rech, Jérôme, Guynet, Catherine, Dauverd-Girault, Julie, Cury, Jean, Rocha, Eduardo, Junier, Ivan, Cornet, François, Espéli, Olivier, espeli, olivier, Appel à projets générique - Génèse et maintenance des chromosomes secondaire bactériens - - MAGISBAC2014 - ANR-14-CE10-0007 - Appel à projets générique - VALID, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de microbiologie et génétique moléculaires - UMR5100 (LMGM), Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Génomique évolutive des Microbes / Microbial Evolutionary Genomics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Biologie Computationnelle et Mathématique (TIMC-IMAG-BCM), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Institut Jean Roger, This work as funded by ANR ANR-14-CE10-0007-01 to OE, FC and ER by the CNRS PICS initiative to OE and IJ and by the Foundation ARC (PJA 20171206119) to OE, ANR-14-CE10-0007,MAGISBAC,Génèse et maintenance des chromosomes secondaire bactériens(2014), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de microbiologie et génétique moléculaires (LMGM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL), Génétique des Interactions macromoléculaires, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Génomique et Évolution des Microorganismes (TIMC-GEM ), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC ), IMAG-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-IMAG-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Biologie Computationnelle et Modélisation (TIMC-BCM ), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, chemistry.chemical_compound, 0302 clinical medicine, Plasmid, Structural Biology, Chromosome Segregation, chromosome, Replicon, 0303 health sciences, Chromosomes, Bacterial, partition, segregation, Cell biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: DNA, Circular, polymer unmixing, DNA, Circular, Intracellular, Plasmids, DNA, Bacterial, MESH: Chromosomes, Bacterial, signal transduction and intracellular signaling Keywords: plasmid, MESH: Biological Transport, MESH: Chromosome Segregation, MESH: Replicon, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Bacterial genome size, Biology, MESH: Enterobacteriaceae, 03 medical and health sciences, Enterobacteriaceae, trafficking, MESH: Plasmids, plasmid, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Nucleoid, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Molecular Biology, 030304 developmental biology, spatiotemporal organization, Chromosome, Biological Transport, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, biochemical phenomena, metabolism, and nutrition, MESH: DNA, Bacterial, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Section/Category: Sorting, chemistry, Cytoplasm, bacteria, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 030217 neurology & neurosurgery, DNA
Abstract

International audience; Bacterial genomes, organized intracellularly as nucleoids, are composed of a main chromosome coexisting with different types of secondary replicons. Secondary replicons are major drivers of 16 bacterial adaptation by gene exchange. They are highly diverse in type and size, ranging from less than 2 to more than 1000 kb, and must integrate with bacterial physiology, including to the nucleoid dynamics, to limit detrimental costs leading to their counter-selection. We show that large DNA circles, whether from a natural plasmid or excised from the chromosome tend to localize in a dynamic manner in a zone separating the nucleoid from the cytoplasm at the edge of the nucleoid.This localization is in good agreement with in silico simulations of DNA circles in the nucleoid volume. Subcellular positioning systems counteract this tendency, allowing replicons to enter the nucleoid space. In enterobacteria, these systems are found in replicons above 25 kb, defining the limit with small randomly segregated plasmids. Larger replicons carry at least one of the three described family of systems, ParAB, ParRM and StbA. Replicons above 180 kb all carry a ParAB system, suggesting this system is specifically required in the cases of large replicons. Simulations demonstrated that replicon size profoundly affects localization, compaction and dynamics of DNA circles in the nucleoid volume. The present work suggests that presence of partition systems on the larger plasmids or chromids is not only due to selection for accurate segregation but also to counteract their unmixing with the chromosome and consequent exclusion from the nucleoid.

Published
2020
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2. Comprendre et inférer la transmission culturelle du succès reproducteur

Author

Guez, Jérémy, Achaz, Guillaume, Bienvenu, François, Cury, Jean, Toupance, Bruno, Heyer, Evelyne, Jay, Flora, Austerlitz, Frederic, Éco-Anthropologie (EA), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Interdisciplinaire des Sciences du Numérique (LISN), Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Collège de France (CdF (institution)), Institute for Theoretical Studies of ETH Zürich (ETH-ITS), TAckling the Underspecified (TAU), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire de Recherche en Informatique (LRI), CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Bioinformatique (LRI) (BioInfo - LRI), Laboratoire de Recherche en Informatique (LRI), and CNRS

Subjects
[SDV]Life Sciences [q-bio]
Abstract

International audience

Published
2022

3. dnadna: DEEP NEURAL ARCHITECTURES FOR DNA - A DEEP LEARNING FRAMEWORK FOR POPULATION GENETIC INFERENCE

Author

Sanchez, Théophile, Madison Bray, Erik, Jobic, Pierre, Guez, Jérémy, Letournel, Anne-Catherine, Charpiat, Guillaume, Cury, Jean, Jay, Flora, Laboratoire Interdisciplinaire des Sciences du Numérique (LISN), CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Accompagnement et Soutien aux Activités de Recherche & Développement (ASARD), CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Éco-Anthropologie (EAE), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), TAckling the Underspecified (TAU), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Interdisciplinaire des Sciences du Numérique (LISN), BioInformatique (BioInfo), and CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Science des Données (SDD)

Subjects
[SDV.GEN]Life Sciences [q-bio]/Genetics, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], deep neural networks, software, population genetics, genomic data, supervised learning, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI]
Abstract

We present dnadna, a flexible python-based software for deep learning inference in population genetics. It is task-agnostic and aims at facilitating the development, reproducibility, dissemination, and reusability of neural networks designed for genetic polymorphism data. dnadna defines multiple user-friendly workflows. First, users can implement new architectures and tasks, while benefiting from dnadna input/output and other utility functions, training procedure and test environment, which not only saves time but also decreases the probability of bugs. Second, implemented networks can be re-optimized based on user-specified training sets and/or tasks. Finally, users can apply pretrained networks in order to predict evolutionary history from alternative real or simulated genetic datasets, without the need of extensive knowledge in deep learning. Thanks to dnadna, newly implemented architectures and pretrained networks are easily shareable with the community for further benchmarking or applications. dnadna comes with a peer-reviewed exchangeable neural network allowing demographic inference from SNP data, that can be used directly or retrained to solve other tasks. Toy networks are also available to ease the exploration of the software, and we expect that the range of available architectures will keep expanding thanks to contributions from the community.

Published
2021

4. dnadna: DEEP NEURAL ARCHITECTURES FOR DNA - A DEEP LEARNING FRAMEWORK FOR POPULATION GENETIC INFERENCE

Author

Sanchez, Théophile, Madison Bray, Erik, Jobic, Pierre, Guez, Jérémy, Charpiat, Guillaume, Cury, Jean, Jay, Flora, Laboratoire Interdisciplinaire des Sciences du Numérique (LISN), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec, Éco-Anthropologie (EAE), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), TAckling the Underspecified (TAU), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Interdisciplinaire des Sciences du Numérique (LISN), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec, BioInformatique (BioInfo), and Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-Science des Données (SDD)

Subjects
[SDV.GEN]Life Sciences [q-bio]/Genetics, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], deep neural networks, software, population genetics, genomic data, supervised learning, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI]
Abstract

We present dnadna, a flexible python-based software for deep learning inference in population genetics. It is task-agnostic and aims at facilitating the development, reproducibility, dissemination, and reusability of neural networks designed for genetic polymorphism data. dnadna defines multiple user-friendly workflows. First, users can implement new architectures and tasks, while benefiting from dnadna input/output and other utility functions, training procedure and test environment, which not only saves time but also decreases the probability of bugs. Second, implemented networks can be re-optimized based on user-specified training sets and/or tasks. Finally, users can apply pretrained networks in order to predict evolutionary history from alternative real or simulated genetic datasets, without the need of extensive knowledge in deep learning. Thanks to dnadna, newly implemented architectures and pretrained networks are easily shareable with the community for further benchmarking or applications. dnadna comes with a peer-reviewed exchangeable neural network allowing demographic inference from SNP data, that can be used directly or retrained to solve other tasks. Toy networks are also available to ease the exploration of the software, and we expect that the range of available architectures will keep expanding thanks to contributions from the community.

Published
2021

5. Intracellular positioning systems limit the entropic eviction of 1 secondary replicons toward the nucleoid edges in bacterial cells

Author

Planchenault, Charlène, Pons, Marine, Schiavon, Caroline, Siguier, Patricia, Rech, Jérôme, Guynet, Catherine, Dauverd -Girault, Julie, Cury, Jean, Rocha, Eduardo, Junier, Ivan, Cornet, François, Espéli, Olivier, Centre interdisciplinaire de recherche en biologie (CIRB), Collège de France (CdF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-PSL Research University (PSL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de microbiologie et génétique moléculaires (LMGM), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Génomique évolutive des Microbes / Microbial Evolutionary Genomics, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Biologie Computationnelle et Mathématique (TIMC-IMAG-BCM), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut Jean Roget, This work as funded by ANR ANR-14-CE10-0007-01 to OE, FC and ER by the CNRS PICS initiative to OE and IJ and by the Foundation ARC (PJA 20171206119) to OE, and ANR-14-CE10-0007,MAGISBAC,Génèse et maintenance des chromosomes secondaire bactériens(2014)

Subjects
bacteria, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], biochemical phenomena, metabolism, and nutrition, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

International audience; Bacterial genomes, organized intracellularly as nucleoids, are composed of a main chromosome coexisting with different types of secondary replicons. Secondary replicons are major drivers of 16 bacterial adaptation by gene exchange. They are highly diverse in type and size, ranging from less than 2 to more than 1000 kb, and must integrate with bacterial physiology, including to the nucleoid dynamics, to limit detrimental costs leading to their counter-selection. We show that large DNA circles, whether from a natural plasmid or excised from the chromosome tend to localize in a dynamic manner in a zone separating the nucleoid from the cytoplasm at the edge of the nucleoid.This localization is in good agreement with in silico simulations of DNA circles in the nucleoid volume. Subcellular positioning systems counteract this tendency, allowing replicons to enter the nucleoid space. In enterobacteria, these systems are found in replicons above 25 kb, defining the limit with small randomly segregated plasmids. Larger replicons carry at least one of the three described family of systems, ParAB, ParRM and StbA. Replicons above 180 kb all carry a ParAB system, suggesting this system is specifically required in the cases of large replicons. Simulations demonstrated that replicon size profoundly affects localization, compaction and dynamics of DNA circles in the nucleoid volume. The present work suggests that presence of partition systems on the larger plasmids or chromids is not only due to selection for accurate segregation but also to counteract their unmixing with the chromosome and consequent exclusion from the nucleoid.

Published
2019
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6. Evolutionary genomics of conjugative elements and integrons

Author

Cury, Jean, Génomique évolutive des Microbes / Microbial Evolutionary Genomics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Sorbonne Paris Cité, Eduardo Pimentel Cachapuz Rocha, and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
Bioinformatique, Bioinformatics, structural biology and genomics, biologie structurale et génomique, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

No abstract; Pas de résumé

Published
2017

7. Génomique évolutive des éléments conjugués et des intégrons

Author

Cury, Jean, Génomique évolutive des Microbes / Microbial Evolutionary Genomics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Sorbonne Paris Cité, and Eduardo Pimentel Cachapuz Rocha

Subjects
Bioinformatique, Bioinformatics, structural biology and genomics, biologie structurale et génomique, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

No abstract; Pas de résumé

Published
2017

8. Differences in Integron Cassette Excision Dynamics Shape a Trade-Off between Evolvability and Genetic Capacitance

Author

Loot, Céline, Nivina, Aleksandra, Cury, Jean, Escudero, José, Ducos-Galand, Magaly, Bikard, David, Rocha, Eduardo, Mazel, Didier, Plasticité du Génome Bactérien - Bacterial Genome Plasticity (PGB), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Génomique évolutive des Microbes / Microbial Evolutionary Genomics, This work was supported by the Institut Pasteur, the Centre National de la Recherche Scientifique, Fondation pour la Recherche Médicale (project DBF20160635736), the French Government Investissement d’Avenir program Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (ANR-10-LABX-62-IBEID), the French National Research Agency (ANR-12-BLAN-DynamINT), the European Union Seventh Framework Program (FP7-HEALTH-2011-single-stage), the 'Evolution and Transfer Of Antibiotic Resistance' (EvoTAR), Paris Descartes University—Sorbonne Paris Cité, Fondation pour la Recherche Médicale (FDT20150532465) and École Doctorale Frontières du Vivant (FdV)—Programme Bettencourt (to A.N.), Marie Curie Intra-European Fellowship for Career Development (FP-7-PEOPLE-2011-IEF, ICADIGE) (to J.A.E.), and European Research Council grant (EVOMOBILOME grant 281605) (to E.P.C.R. and J.C.)., We thank Claire Vit for helpful discussions and Sebastian Aguilar Pierlé for reading the manuscript., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-12-BSV3-0015,DynamINT,Recombination des cassettes d'intégron: dynamique in vivo et in vitro(2012), European Project: 282004,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,EVOTAR(2011), European Project: 303022,EC:FP7:PEOPLE,FP7-PEOPLE-2011-IEF,ICADIGE(2012), European Project: 281605,EC:FP7:ERC,ERC-2011-StG_20101109,EVOMOBILOME(2012), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Plasticité du Génome Bactérien, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], and ANR-10-LABX-62-IBEID,IBEID,Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases'(2010)

Subjects
Recombination, Genetic, replication, integron, Bacteria, MESH: Interspersed Repetitive Sequence, MESH: Adaptation, Biological, [SDV]Life Sciences [q-bio], Adaptation, Biological, site-specific recombination, Computational Biology, attC sites, Microbiology, QR1-502, Integrons, MESH: Integrons, Evolution, Molecular, Interspersed Repetitive Sequences, MESH: Bacteria, MESH: Recombination, Genetic, cassette dynamics, MESH: Evolution, Molecular, Research Article, MESH: Computational Biology
Abstract

Integrons ensure a rapid and “on demand” response to environmental stresses driving bacterial adaptation. They are able to capture, store, and reorder functional gene cassettes due to site-specific recombination catalyzed by their integrase. Integrons can be either sedentary and chromosomally located or mobile when they are associated with transposons and plasmids. They are respectively called sedentary chromosomal integrons (SCIs) and mobile integrons (MIs). MIs are key players in the dissemination of antibiotic resistance genes. Here, we used in silico and in vivo approaches to study cassette excision dynamics in MIs and SCIs. We show that the orientation of cassette arrays relative to replication influences attC site folding and cassette excision by placing the recombinogenic strands of attC sites on either the leading or lagging strand template. We also demonstrate that stability of attC sites and their propensity to form recombinogenic structures also regulate cassette excision. We observe that cassette excision dynamics driven by these factors differ between MIs and SCIs. Cassettes with high excision rates are more commonly found on MIs, which favors their dissemination relative to SCIs. This is especially true for SCIs carried in the Vibrio genus, where maintenance of large cassette arrays and vertical transmission are crucial to serve as a reservoir of adaptive functions. These results expand the repertoire of known processes regulating integron recombination that were previously established and demonstrate that, in terms of cassette dynamics, a subtle trade-off between evolvability and genetic capacitance has been established in bacteria., IMPORTANCE The integron system confers upon bacteria a rapid adaptation capability in changing environments. Specifically, integrons are involved in the continuous emergence of bacteria resistant to almost all antibiotic treatments. The international situation is critical, and in 2050, the annual number of deaths caused by multiresistant bacteria could reach 10 million, exceeding the incidence of deaths related to cancer. It is crucial to increase our understanding of antibiotic resistance dissemination and therefore integron recombination dynamics to find new approaches to cope with the worldwide problem of multiresistance. Here, we studied the dynamics of recombination and dissemination of gene encoding cassettes carried on integrons. By combining in silico and in vivo analyses, we show that cassette excision is highly regulated by replication and by the intrinsic properties of cassette recombination sites. We also demonstrated differences in the dynamics of cassette recombination between mobile and sedentary chromosomal integrons (MIs and SCIs). For MIs, a high cassette recombination rate is favored and timed to conditions when generating diversity (upon which selection can act) allows for a rapid response to environmental conditions and stresses. In contrast, for SCIs, cassette excisions are less frequent, limiting cassette loss and ensuring a large pool of cassettes. We therefore confirm a role of SCIs as reservoirs of adaptive functions and demonstrate that the remarkable adaptive success of integron recombination system is due to its intricate regulation.

Published
2017
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9. The chromosomal organization of horizontal gene transfer in bacteria

Author

Oliveira, Pedro H., Touchon, Marie, Cury, Jean, and Rocha, Eduardo P. C.

Subjects
Bacteria, Gene Transfer, Horizontal, Science, Genetic Variation, lcsh:Q, Chromosomes, Bacterial, lcsh:Science, Homologous Recombination, Author Correction, Article, Genome, Bacterial
Abstract

Bacterial adaptation is accelerated by the acquisition of novel traits through horizontal gene transfer, but the integration of these genes affects genome organization. We found that transferred genes are concentrated in only ~1% of the chromosomal regions (hotspots) in 80 bacterial species. This concentration increases with genome size and with the rate of transfer. Hotspots diversify by rapid gene turnover; their chromosomal distribution depends on local contexts (neighboring core genes), and content in mobile genetic elements. Hotspots concentrate most changes in gene repertoires, reduce the trade-off between genome diversification and organization, and should be treasure troves of strain-specific adaptive genes. Most mobile genetic elements and antibiotic resistance genes are in hotspots, but many hotspots lack recognizable mobile genetic elements and exhibit frequent homologous recombination at flanking core genes. Overrepresentation of hotspots with fewer mobile genetic elements in naturally transformable bacteria suggests that homologous recombination and horizontal gene transfer are tightly linked in genome evolution., Horizontal gene transfer (HGT) is an important mechanism for genome evolution and adaptation in bacteria. Here, Oliveira and colleagues find HGT hotspots comprising ~ 1% of the chromosomal regions in 80 bacterial species.

Published
2017

10. What does mining ICE in bacterial genomes reveal?

Author

Cury, Jean, Abby, Sophie S., Guglielmini, Julien, Garcillán-Barcia, M. Pilar, Cruz, Fernando de la, Touchon, Marie, and Rocha, Eduardo P. C.

Abstract

Resumen del trabajo presentado al Plasmid Biology Meeting, celebrado en Cambridge (UK) del 18 al 23 de septiembre de 2016., Conjugative elements play a major role in bacterial evolution. They have been widely studied when associated with plasmids, however, the role and importance of Integrative and Conjugative Elements (ICE) remain less clear. Yet, it has been shown that ICEs are more abundant than conjugative plasmids in bacterial genomes. Using comparative genomics, we analyzed about 200 ICEs, which we delimited precisely. This unique dataset allowed us to have a more general picture of ICEs. We could outline for the first time their general organization and their relation to their host’s genome. More importantly, we infer some evolutionary properties of ICEs. Indeed we look for a wide range of mobile genetic element associated functions like restriction modification systems, integrons, toxin-antitoxins, entry-exclusion systems, among other functions. This accurate annotation allowed us to better understand ICE’s relationship to its host. This provides quantitative new information on ICEs and allows us to better understand their broader role in the evolution of bacteria.

Published
2016

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