DNA phosphorothioate modification mediated by dnd gene cluster is the first reported DNA skeleton modification. Protein encoded by dnd gene cluster works together to form a multifunctional epigenetic system in microbial genome, which endows microorganisms with many abilities, including antioxidation, restrictive modification, antiviral infection and so on. Interestingly, compared with other modification systems (such as methylation modification), dnd system will bring many survival advantages to microorganisms, but it is scattered in many prokaryotes. In order to solve this ecological paradox, the research team first put forward a scientific hypothesis: in the process of transmission through horizontal gene transfer, PT modification brought by dnd system may affect the gene expression of recipient microorganisms, especially activating the protophage widely distributed in the microbial genome, resulting in the survival disadvantage of recipient microorganisms, thus significantly limiting the spread and distribution of dnd system. In order to test this hypothesis, we systematically analyzed the relationship between dnd gene and gene cluster and the distribution of protophage in bacterial genome, and the results showed that there was a significant negative correlation between them. In addition, the marine filamentous phage SW 1 and its host strain were used to withstand the pressure of Escherichia coli. In-depth analysis of WP3 as a model system shows that PT modification significantly affects the abundance of phage regulatory protein FpsR and its binding affinity with operon, thus relieving the transcription inhibition of SW 1 protophage. In addition, in some bacteria (including Escherichia coli? Escherichia coli, Streptococcus parthenogenes? MR- 1, Streptococcus putrefaction? W3- 18- 1) also confirmed that the horizontal gene transfer of dnd gene cluster was limited by the original phage. Comprehensive competition experiment, transcriptome analysis and modification group analysis showed that PT modification could also affect the high-pressure resistant Streptococcus in marine bacteria, besides the original phage gene. The transcription of many genes related to metabolism and stress resistance in WP3 led to a significant decline in its competitive adaptability.