Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Feb 15;108(7):2963-8.
doi: 10.1073/pnas.1017261108. Epub 2011 Feb 1.

DNA phosphorothioation is widespread and quantized in bacterial genomes

Lianrong Wang  1 , Shi Chen, Kevin L Vergin, Stephen J Giovannoni, Simon W Chan, Michael S DeMott, Koli Taghizadeh, Otto X Cordero, Michael Cutler, Sonia Timberlake, Eric J Alm, Martin F Polz, Jarone Pinhassi, Zixin Deng, Peter C Dedon
Affiliations

DNA phosphorothioation is widespread and quantized in bacterial genomes

Lianrong Wang et al. Proc Natl Acad Sci U S A. .

Abstract

Phosphorothioate (PT) modification of DNA, with sulfur replacing a nonbridging phosphate oxygen, was recently discovered as a product of the dnd genes found in bacteria and archaea. Given our limited understanding of the biological function of PT modifications, including sequence context, genomic frequencies, and relationships to the diversity of dnd gene clusters, we undertook a quantitative study of PT modifications in prokaryotic genomes using a liquid chromatography-coupled tandem quadrupole mass spectrometry approach. The results revealed a diversity of unique PT sequence contexts and three discrete genomic frequencies in a wide range of bacteria. Metagenomic analyses of PT modifications revealed unique ecological distributions, and a phylogenetic comparison of dnd genes and PT sequence contexts strongly supports the horizontal transfer of dnd genes. These results are consistent with the involvement of PT modifications in a type of restriction-modification system with wide distribution in prokaryotes.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Analysis of PT-linked dinucleotides by LC-MS/MS in multiple reaction monitoring mode. All of the 16 possible PT-linked dinucleotides in RP configuration were resolved by reversed-phase HPLC followed by MS/MS detection by using the ion transitions labeled under each dinucleotide. Bold arrow indicates d(GPSA) SP internal standard.
Fig. 2.
Fig. 2.
Correlation between PT sequence contexts and Dnd protein sequences. Phylogenetic analysis reveals a correlation between PT sequence context and four of the Dnd protein sequences, and supports horizontal rather than vertical gene transfer for dnd genes. Dnd protein sequences for 12 strains analyzed here were retrieved from the NCBI Protein database and aligned using Muscle (35) and phylogenetic trees were computed with phyML (36), with phylogenies displayed using iTol (37). The PT sequence context is color-coded as noted in the key.
See this image and copyright information in PMC

References

    1. Eckstein F, Gish G. Phosphorothioates in molecular biology. Trends Biochem Sci. 1989;14:97–100. - PubMed
    1. Wang L, et al. Phosphorothioation of DNA in bacteria by dnd genes. Nat Chem Biol. 2007;3:709–710. - PubMed
    1. Zhou X, Deng Z, Firmin JL, Hopwood DA, Kieser T. Site-specific degradation of Streptomyces lividans DNA during electrophoresis in buffers contaminated with ferrous iron. Nucleic Acids Res. 1988;16:4341–4352. - PMC - PubMed
    1. Ou HY, et al. dndDB: a database focused on phosphorothioation of the DNA backbone. PLoS ONE. 2009;4:e5132. - PMC - PubMed
    1. You D, Wang L, Yao F, Zhou X, Deng Z. A novel DNA modification by sulfur: DndA is a NifS-like cysteine desulfurase capable of assembling DndC as an iron-sulfur cluster protein in Streptomyces lividans. Biochemistry. 2007;46:6126–6133. - PubMed

Publication types

MeSH terms

LinkOut - more resources