Research on Sulfur Modification of DNA Skeleton Receives New Achievements

Shanghai Jiaotong University, Wuhan University and the Massachusetts Institute of Technology jointly cooperated with Wang Lianrong as the first author, Chen Shi and Peter Didan as the co-corresponding author of the paper "DNA phosphorylation modification widely distributed in the bacterial genome "Quantitative Existence" was published in the Proceedings of the National Academy of Sciences recently, which is another new and important development in the field of sulfur modification on the DNA backbone, and the chemical nature of sulfur modification on the DNA backbone was also reported by the team of Deng Zixin and Peter Didan New achievements after continuous cooperation.

The thesis combines high-sensitivity detection and fine quantification. Simultaneous identification of 16 different sequences of phosphorothioated DNA dinucleotides and their chromosome modification frequencies from the femtomolar level (10-12 mol) is achieved. Modified DNA for rapid, efficient, high-throughput, and quantifiable chemical detection. On this basis, unprecedented modifications of new sulfur-modified DNA including d (GPST), d (CPSA), d (TPSA), d (APSA) and d (CPSC), clarified that DNA sulfur modification is from soil microorganisms to marine microorganisms, from plant pathogens to human pathogens, from aerobic bacteria to anaerobic bacteria, and even one of the smallest autonomously growing microorganisms The wide variety of C. Pelagibacter ubique HTCC1002 showed that sulfur modification is a very unique physiological modification that exists widely on the DNA skeleton of natural microorganisms.

In addition, this study also extended the research of DNA sulfur modification to environmental genomics (metagenomics) for the first time. The dnd gene cluster and various sequences of DNA sulfur modification including d (GPSA) were found in the marine environment of Sargassum and Oregon coast waters , D (GPSG), d (GPST), and d (CPSC); at the same time, it was found that the distribution of sulfur-modified microorganisms is related to specific ocean areas and ocean depths. For example, d (GPSG) exists mostly in the sea of ​​Sargassum up to 200 meters deep Deep sea areas, and d (CPSC) exists in various water layers. Phylogenetic tree analysis found that the spread of the dnd gene conformed to the characteristics of horizontal gene transfer, which laid a new foundation for future research on the evolution of the dnd gene cluster and its material exchanges and physiological functions between different microorganisms.

The study also identified part of the genomes of several Vibrio species through second-generation sequencing technology, and the relationship between these genomic information and the DNA skeleton sulfur modification, and found that the DNA sulfur modification on the chromosome is strictly regulated, and its quantitative distribution The frequency conforms to the characteristics of the restriction modification system, corroborating that DNA sulfur modification is associated with a new type of restriction system. In addition, the research method can also be easily extended to the fine chemical structure identification of arsenic-based life. For example, the chemical structure confirmation of arsenic-based life is different from phosphorothioate modification. Arsenic substitution may become the second case after DNA sulfur modification Physiological modifications on the DNA backbone.

Relevant experts evaluated that the recent systematic progress in this field has advanced the research of DNA sulfur modification to a new development stage. Recently, the Chinese team has been invited to write the chapter Phosphorothioation: an unusual post-replicative modification on the DNA backbone for the English monograph DNA replication system.

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