Phosphorothioate (PT) modification by the dnd gene cluster is the first identified DNA backbone modification and constitute an epigenetic system with multiple functions, including antioxidant ability, restriction modification, and virus resistance. Despite these advantages for hosting dnd systems, they are surprisingly distributed sporadically among contemporary prokaryotic genomes. To address this ecological paradox, we systematically investigate the occurrence and phylogeny of dnd systems, and they are suggested to have originated in ancient Cyanobacteria after the Great Oxygenation Event. Interestingly, the occurrence of dnd systems and prophages is significantly negatively correlated. Further, we experimentally confirm that PT modification activates the filamentous phage SW1 by altering the binding affinity of repressor and the transcription level of its encoding gene. Competition assays, concurrent epigenomic and transcriptomic sequencing subsequently show that PT modification affects the expression of a variety of metabolic genes, which reduces the competitive fitness of the marine bacterium Shewanella piezotolerans WP3. Our findings strongly suggest that a series of negative effects on microorganisms caused by dnd systems limit horizontal gene transfer, thus leading to their sporadic distribution. Overall, our study reveals putative evolutionary scenario of the dnd system and provides novel insights into the physiological and ecological influences of PT modification.

Proposed underlying mechanism responsible for the derepression of phage SW1 gene transcription by PT modification

The dnd system with a primordial configuration originated in ancient Cyanobacteria (probably Nostocales)

Reference:

Huahua Jian, Guanpeng Xu, Yi Yi, Yali Hao, Yinzhao Wang, Lei Xiong, Siyuan Wang, Shun-zhang Liu, Canxing Meng, Jiahua Wang, Yue Zhang, Chao Chen, Xiaoyuan Feng, Haiwei Luo, Hao Zhang, Xingguo Zhang, Lianrong Wang, Zhijun Wang, Zixin Deng, Xiang Xiao*. (2021). The origin and impeded dissemination of the DNA phosphorothioation system in prokaryotes. Nature Communications, 12(1): 6382.

Link: www.nature.com/articles/s41467-021-26636-7#citeas