DNA Methylation Assessed by SMRT Sequencing Is Linked to Mutations in Neisseria meningitidis Isolates. SMRT Sequencing Neisseria meningitidis

Aims: The extent and functional consequences of DNA methylation in the human pathogen Neisseria meningitidis is incompletely characterized. Materials & methods: We applied SMRT sequencing (Pacific Biosciences) to assess the genome-wide DNA modification profiles of two closely related N. meningitidis strains. Results: Our results revealed high divergence in DNA methylation predominantly driven by phase variability, represented by the discovery of one novel strain-specific target motif AC6mACC of the DNA methyltransferase modA12. We detected clear biases in the positional distribution of methylated target sites and prominent colocalization of methylated bases with Single Nucleotide Polymorphisms (SNPs) in a collection of N. meningitidis genomes. Conclusions: These findings suggest more diverse roles of DNA methylation and Restriction-Modification systems in the evolution of prokaryotic genomes.

研究目的（Aims）：人类病原体脑膜炎奈瑟菌（Neisseria meningitidis）的DNA甲基化分布范围及其功能后果尚未得到充分表征。
材料与方法（Materials & methods）：本研究应用单分子实时测序（SMRT sequencing，Pacific Biosciences）技术，对两株亲缘关系相近的脑膜炎奈瑟菌菌株的全基因组DNA修饰谱进行评估。
结果（Results）：本研究结果显示，DNA甲基化存在高度差异，该差异主要由相变异驱动；本次研究还发现了DNA甲基转移酶（DNA methyltransferase）modA12的一个全新菌株特异性靶基序AC6mACC。我们在脑膜炎奈瑟菌基因组集合中检测到甲基化靶位点的位置分布存在显著偏倚，且甲基化碱基与单核苷酸多态性（Single Nucleotide Polymorphisms，SNPs）存在显著共定位现象。
结论（Conclusions）：上述研究结果表明，DNA甲基化与限制修饰系统（Restriction-Modification systems）在原核生物基因组进化中所发挥的作用更为多样。