N⁶-Adenine DNA methyltransferases associated with some Type I and Type III restriction-modification (R-M) systems are able to undergo phase variation, randomly switching expression ON or OFF by varying the length of locus-encoded simple sequence repeats (SSRs). This variation of methyltransferase expression results in genome-wide methylation differences and global changes in gene expression. These epigenetic regulatory systems are called phasevarions, phase-variable regulons, and are widespread in bacteria. A distinct switching system has also been described in Type I R-M systems, based on recombination-driven changes in hsdS genes, which dictate the DNA target site. In order to determine the prevalence of recombination-driven phasevarions, we generated a program called RecombinationRepeatSearch to interrogate REBASE and identify the presence and number of inverted repeats of hsdS downstream of Type I R-M loci. We report that 3.9% of Type I R-M systems have duplicated variable hsdS genes containing inverted repeats capable of phase variation. We report the presence of these systems in the major pathogens Enterococcus faecalis and Listeria monocytogenes, which could have important implications for pathogenesis and vaccine development. These data suggest that in addition to SSR-driven phasevarions, many bacteria have independently evolved phase-variable Type I R-M systems via recombination between multiple, variable hsdS genes.

中文翻译：

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REBASE的系统分析确定了多个具有重复的，不同的hsdS特异性基因的I型限制性修饰系统，这些基因可以通过重组来切换系统特异性。

与某些I型和III型限制性修饰（RM）系统相关的N ^6-腺嘌呤DNA甲基转移酶能够进行相变，通过改变基因座编码的简单序列重复序列（SSR）的长度来随机将表达打开或关闭。甲基转移酶表达的这种变化导致基因组范围内的甲基化差异和基因表达的整体变化。这些表观遗传调控系统称为相变体，相变调节剂，并广泛存在于细菌中。基于hsdS中重组驱动的变化，在I型RM系统中还描述了一种独特的交换系统基因，决定了DNA靶位点。为了确定重组驱动相变的普遍性，我们生成了一个名为RecombinationRepeatSearch的程序来询问REBASE并确定I型RM基因座下游hsdS反向重复序列的存在和数目。我们报告说3.9％的I型RM系统具有重复的可变hsdS基因，该基因包含能够进行相变的反向重复。我们报告了这些系统在粪肠球菌和单核细胞增生李斯特菌的主要病原体中的存在，这可能对发病机理和疫苗开发具有重要意义。这些数据表明，除了SSR驱动的相变，许多细菌还通过多个可变的hsdS基因之间的重组独立地进化了相变I型RM系统。