Institute for Glycomics, Griffith University Gold Coast, Queensland, Australia.
PLoS One. 2012;7(3):e32337. doi: 10.1371/journal.pone.0032337. Epub 2012 Mar 23.
Phase variable restriction-modification (R-M) systems have been identified in a range of pathogenic bacteria. In some it has been demonstrated that the random switching of the mod (DNA methyltransferase) gene mediates the coordinated expression of multiple genes and constitutes a phasevarion (phase variable regulon). ModA of Neisseria and Haemophilus influenzae contain a highly variable, DNA recognition domain (DRD) that defines the target sequence that is modified by methylation and is used to define modA alleles. 18 distinct modA alleles have been identified in H. influenzae and the pathogenic Neisseria. To determine the origin of DRD variability, the 18 modA DRDs were used to search the available databases for similar sequences. Significant matches were identified between several modA alleles and mod gene from distinct bacterial species, indicating one source of the DRD variability was via horizontal gene transfer. Comparison of DRD sequences revealed significant mosaicism, indicating exchange between the Neisseria and H. influenzae modA alleles. Regions of high inter- and intra-allele similarity indicate that some modA alleles had undergone recombination more frequently than others, generating further diversity. Furthermore, the DRD from some modA alleles, such as modA12, have been transferred en bloc to replace the DRD from different modA alleles.
相变异限制修饰（R-M）系统已在多种致病菌中被发现。在某些致病菌中，随机切换修饰（DNA 甲基转移酶）基因介导了多个基因的协调表达，并构成了一个相变异区（相变异调控子）。脑膜炎奈瑟菌和流感嗜血杆菌的 ModA 含有一个高度可变的 DNA 识别结构域（DRD），该结构域定义了被甲基化修饰的靶序列，并用于定义 ModA 等位基因。已在流感嗜血杆菌和致病性奈瑟菌中鉴定出 18 种不同的 ModA 等位基因。为了确定 DRD 变异性的起源，将 18 种 ModA DRD 用于搜索可用数据库中的相似序列。在几个 ModA 等位基因和不同细菌物种的 Mod 基因之间发现了显著的匹配，表明 DRD 变异性的一个来源是通过水平基因转移。DRD 序列的比较揭示了显著的镶嵌性，表明奈瑟菌和流感嗜血杆菌 ModA 等位基因之间存在交换。高的种内和种间相似性区域表明，一些 ModA 等位基因比其他等位基因更频繁地经历了重组，产生了更多的多样性。此外，一些 ModA 等位基因（如 modA12）的 DRD 已经被整体转移，以取代不同 ModA 等位基因的 DRD。
