title: Novel genomic rearrangements mediated by multiple genetic elements in Streptococcus pyogenes M23ND confer potential for evolutionary persistence.
abstract: Symmetric genomic rearrangements around replication axes in genomes are commonly observed in prokaryotic genomes, including Group A Streptococcus (GAS). However, asymmetric rearrangements are rare. Our previous studies showed that the hypervirulent invasive GAS strain, M23ND, containing an inactivated transcriptional regulator system, covRS, exhibits unique extensive asymmetric rearrangements, which reconstructed a genomic structure distinct from other GAS genomes. In the current investigation, we identified the rearrangement events and examined the genetic consequences and evolutionary implications underlying the rearrangements. By comparison with a close phylogenetic relative, M18-MGAS8232, we propose a molecular model wherein a series of asymmetric rearrangements have occurred in M23ND, involving translocations, inversions and integrations mediated by multiple factors, viz., rRNA-comX (factor for late competence), transposons and phage-encoded gene segments. Assessments of the cumulative gene orientations and GC skews reveal that the asymmetric genomic rearrangements did not affect the general genomic integrity of the organism. However, functional distributions reveal re-clustering of a broad set of CovRS-regulated actively transcribed genes, including virulence factors and metabolic genes, to the same leading strand, with high confidence (p-value ~10-10). The re-clustering of the genes suggests a potential selection advantage for the spatial proximity to the transcription complexes, which may contain the global transcriptional regulator, CovRS, and other RNA polymerases. Their proximities allow for efficient transcription of the genes required for growth, virulence and persistence. A new paradigm of survival strategies of GAS strains is provided through multiple genomic rearrangements, while, at the same time, maintaining genomic integrity.
authors.affiliation: W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Yun-Juan
authors.initials: YJ
authors.lastname: Bao
authors.affiliation: W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN 46556, USA.|Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Liang
authors.affiliation: W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN 46556, USA.|Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Mayfield
authors.affiliation: Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: William M
authors.initials: WM
authors.lastname: McShan
authors.affiliation: W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN 46556, USA.|Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Shaun W
authors.initials: SW
authors.lastname: Lee
authors.affiliation: W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN 46556, USA.|Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Ploplis
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.|W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Castellino
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D004251:DNA Transposable Elements / Q000235:genetics*; D012321:DNA-Directed RNA Polymerases / Q000235:genetics; D015321:Gene Rearrangement / Q000235:genetics*; D016680:Genome, Bacterial / Q000235:genetics; D000071677:Histidine Kinase; D059765:Homologous Recombination / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013297:Streptococcus pyogenes / Q000235:genetics* / Q000472:pathogenicity; D037521:Virulence Factors / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; C432143:CsrR protein, Streptococcus pyogenes; D004251:DNA Transposable Elements; D047908:Intracellular Signaling Peptides and Proteins; D012097:Repressor Proteins; D037521:Virulence Factors; C534547:CovS protein, Streptococcus pyogenes; D000071677:Histidine Kinase; D012321:DNA-Directed RNA Polymerases