Novel genomic island modifies DNA with 7-deazaguanine derivatives

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 113; no. 11; pp. E1452 - E1459
• Main Authors: Thiaville, Jennifer J., Kellner, Stefanie M., Yuan, Yifeng, Hutinet, Geoffrey, Thiaville, Patrick C., Jumpathong, Watthanachai, Mohapatra, Susovan, Brochier-Armanet, Celine, Letarov, Andrey V., Hillebrand, Roman, Malik, Chanchal K., Rizzo, Carmelo J., Dedon, Peter C., de Crécy-Lagard, Valérie
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 15-03-2016; National Acad Sciences
• Series: PNAS Plus
• Subjects: Amino Acid Sequence; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biological Sciences; Coliphages - genetics; Coliphages - metabolism; Comamonas testosteroni; Comparative analysis; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - analysis; Deoxyguanosine - metabolism; Deoxyribonucleic acid; DNA; DNA, Bacterial - chemistry; DNA, Bacterial - genetics; DNA, Bacterial - metabolism; Enterobacteriaceae; Escherichia coli; Gene Transfer, Horizontal; Genomic Islands; Gram-negative bacteria; Guanine - analogs & derivatives; Guanine - chemistry; Guanine - metabolism; Guanosine - analogs & derivatives; Guanosine - metabolism; Life Sciences; Molecular Sequence Data; Multigene Family; Mutation; Phylogenetics; Phylogeny; Plasmids; PNAS Plus; Purines - analysis; RNA, Transfer - genetics; RNA, Transfer - metabolism; Salmonella enterica; Salmonella enterica - genetics; Salmonella enterica - metabolism; Salmonella typhimurium - genetics; Transfer RNA; DNA modification; restriction–modification; queuosine; comparative genomics; 7-deazaguanine
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1518570113

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 9g, 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.