title: Novel genomic island modifies DNA with 7-deazaguanine derivatives.
abstract: The discovery of ∼20-kb gene clusters containing a family of paralogs of tRNA guanosine transglycosylase genes, called tgtA5, alongside 7-cyano-7-deazaguanine (preQ0) synthesis and DNA metabolism genes, led to the hypothesis that 7-deazaguanine derivatives are inserted in DNA. This was established by detecting 2'-deoxy-preQ0 and 2'-deoxy-7-amido-7-deazaguanosine in enzymatic hydrolysates of DNA extracted from the pathogenic, Gram-negative bacteria Salmonella enterica serovar Montevideo. These modifications were absent in the closely related S. enterica serovar Typhimurium LT2 and from a mutant of S Montevideo, each lacking the gene cluster. This led us to rename the genes of the S. Montevideo cluster as dpdA-K for 7-deazapurine in DNA. Similar gene clusters were analyzed in ∼150 phylogenetically diverse bacteria, and the modifications were detected in DNA from other organisms containing these clusters, including Kineococcus radiotolerans, Comamonas testosteroni, and Sphingopyxis alaskensis Comparative genomic analysis shows that, in Enterobacteriaceae, the cluster is a genomic island integrated at the leuX locus, and the phylogenetic analysis of the TgtA5 family is consistent with widespread horizontal gene transfer. Comparison of transformation efficiencies of modified or unmodified plasmids into isogenic S. Montevideo strains containing or lacking the cluster strongly suggests a restriction-modification role for the cluster in Enterobacteriaceae. Another preQ0 derivative, 2'-deoxy-7-formamidino-7-deazaguanosine, was found in the Escherichia coli bacteriophage 9 g, as predicted from the presence of homologs of genes involved in the synthesis of the archaeosine tRNA modification. These results illustrate a deep and unexpected evolutionary connection between DNA and tRNA metabolism.
authors.affiliation: Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611-0700;
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Thiaville
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors.forename: Stefanie M
authors.initials: SM
authors.lastname: Kellner
authors.affiliation: Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611-0700;
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611-0700;
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Hutinet
authors.affiliation: Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611-0700;
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Thiaville
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors.forename: Watthanachai
authors.initials: W
authors.lastname: Jumpathong
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors.forename: Susovan
authors.initials: S
authors.lastname: Mohapatra
authors.affiliation: Université de Lyon, Université Lyon 1, CNRS, UMR5558, Laboratoire de Biométrie et Biologie Évolutive, F-69622 Villeurbanne, France;
authors.forename: Celine
authors.initials: C
authors.lastname: Brochier-Armanet
authors.affiliation: Winogradsky Institute of Microbiology, Research Center of Biotechnology of Russian Academy of Sciences, Moscow 119071, Russia;
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Letarov
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors.forename: Roman
authors.initials: R
authors.lastname: Hillebrand
authors.affiliation: Department of Chemistry, Vanderbilt University, Nashville, TN 37235;
authors.forename: Chanchal K
authors.initials: CK
authors.lastname: Malik
authors.affiliation: Department of Chemistry, Vanderbilt University, Nashville, TN 37235; Department of Biochemistry, Center in Molecular Toxicology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232;
authors.forename: Carmelo J
authors.initials: CJ
authors.lastname: Rizzo
authors.affiliation: Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139; Infectious Disease Interdisciplinary Research Group, Campus for Research Excellence and Technological Enterprise, Singapore-MIT Alliance for Research and Technology, Singapore 138602; vcrecy@ufl.edu pcdedon@mit.edu.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Dedon
authors.affiliation: Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611-0700; University of Florida Genetics Institute, Gainesville, FL 32610 vcrecy@ufl.edu pcdedon@mit.edu.
authors.forename: Valérie
authors.initials: V
authors.lastname: de Crécy-Lagard
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003090:Coliphages / Q000235:genetics / Q000378:metabolism; D004269:DNA, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D022761:Gene Transfer, Horizontal; D044404:Genomic Islands; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D006151:Guanosine / Q000031:analogs & derivatives / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D010802:Phylogeny; D011687:Purines / Q000032:analysis; D012343:RNA, Transfer / Q000235:genetics / Q000378:metabolism; D019779:Salmonella enterica / Q000235:genetics* / Q000378:metabolism; D012486:Salmonella typhimurium / Q000235:genetics
chemical_list: C512929:7-deazapurine; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D011687:Purines; D006151:Guanosine; C081066:archaeosine; D006147:Guanine; D012343:RNA, Transfer; D003849:Deoxyguanosine; C066856:7-deazaguanine
keywords: 7-deazaguanine; DNA modification; comparative genomics; queuosine; restriction–modification