Department of Chemical Engineering, University of Washington, Seattle 98195, WA, USA.
Department of Chemical Engineering, University of Washington, Seattle 98195, WA, USA; eScience Institute, University of Washington, Seattle 98185, WA, USA.
Plasmid. 2019 Mar;102:10-18. doi: 10.1016/j.plasmid.2019.02.003. Epub 2019 Feb 22.
Mosaic plasmids, plasmids composed of genetic elements from distinct sources, are associated with the spread of antibiotic resistance genes. Transposons are considered the primary mechanism for mosaic plasmid formation, though other mechanisms have been observed in specific instances. The frequency with which mosaic plasmids have been described suggests they may play an important role in plasmid population dynamics. Our survey of the confirmed plasmid sequences available from complete and draft genomes in the RefSeq database shows that 46% of them fit a strict definition of mosaic. Mosaic plasmids are also not evenly distributed over the taxa represented in the database. Plasmids from some genera, including Piscirickettsia and Yersinia, are almost all mosaic, while plasmids from other genera, including Borrelia, are rarely mosaic. While some mosaic plasmids share identical regions with hundreds of others, the median mosaic plasmid only shares with 8 other plasmids. When considering only plasmids from finished genomes (51.6% of the total), mosaic plasmids have significantly higher proportions of transposase and antibiotic resistance genes. Conversely, only 56.6% of mosaic fragments (DNA fragments shared between mosaic plasmids) contain a recognizable transposase gene, and only 1.2% of mosaic fragments are flanked by inverted repeats. Mosaic fragments associated with the IS26 transposase gene are 3.8-fold more abundant than any other sequence shared between mosaic plasmids in the database, though this is at least partly due to overrepresentation of Enterobacteriaceae plasmids. Mosaic plasmids are a complicated trait of some plasmid populations, only partly explained by transposition. Though antibiotic resistance genes led to the identification of many mosaic plasmids, mosaic plasmids are a broad phenomenon encompassing many more traits than just antibiotic resistance. Further research will be required to determine the influence of ecology, host repair mechanisms, conjugation, and plasmid host range on the formation and influence of mosaic plasmids. AUTHOR SUMMARY: Plasmids are extrachromosomal genetic entities that are found in many prokaryotes. They serve as flexible storage for genes, and individual cells can make substantial changes to their characteristics by acquiring, losing, or modifying a plasmid. In some pathogenic bacteria, such as Escherichia coli, antibiotic resistance genes are known to spread primarily on plasmids. By analyzing a database of 8592 plasmid sequences we determined that many of these plasmids have exchanged genes with each other, becoming mosaics of genes from different sources. We next separated these plasmids into groups based on the organism they were isolated from and found that different groups had different fractions of mosaic plasmids. This result was unexpected and suggests that the mechanisms and selective pressures causing mosaic plasmids do not occur evenly over all species. It also suggests that plasmids may provide different levels of potential variation to different species. This work uncovers a previously unrecognized pattern in plasmids across prokaryotes, that could lead to new insights into the evolutionary role that plasmids play.
镶嵌质粒是由不同来源的遗传元件组成的质粒，与抗生素耐药基因的传播有关。转座子被认为是形成镶嵌质粒的主要机制，但在特定情况下也观察到了其他机制。描述的镶嵌质粒的频率表明，它们可能在质粒种群动态中发挥重要作用。我们对 RefSeq 数据库中完整和草图基因组中已确认的质粒序列进行了调查，结果显示，其中 46%符合严格的镶嵌定义。镶嵌质粒在数据库中代表的分类群中也不是均匀分布的。一些属的质粒，包括 Piscirickettsia 和 Yersinia，几乎都是镶嵌的，而其他属的质粒，如 Borrelia，很少是镶嵌的。虽然一些镶嵌质粒与数百个其他质粒共享相同的区域，但中位数镶嵌质粒仅与其他 8 个质粒共享。当仅考虑来自完成基因组的质粒（占总数的 51.6%）时，镶嵌质粒具有更高比例的转座酶和抗生素耐药基因。相反，只有 56.6%的镶嵌片段（镶嵌质粒之间共享的 DNA 片段）含有可识别的转座酶基因，只有 1.2%的镶嵌片段被反向重复序列包围。与 IS26 转座酶基因相关的镶嵌片段比数据库中镶嵌质粒之间共享的任何其他序列丰富 3.8 倍，尽管这至少部分是由于肠杆菌科质粒的过度表达。尽管抗生素耐药基因导致了许多镶嵌质粒的鉴定，但镶嵌质粒是一种复杂的质粒群体特征，不仅仅是转座解释了这一特征。镶嵌质粒是许多更多特征的广泛现象，而不仅仅是抗生素耐药性。需要进一步研究才能确定生态、宿主修复机制、接合和质粒宿主范围对镶嵌质粒的形成和影响的影响。
质粒是许多原核生物中发现的染色体外遗传实体。它们作为基因的灵活存储库，单个细胞可以通过获取、丢失或修饰质粒来对其特性进行实质性改变。在一些致病菌中，如大肠杆菌，抗生素耐药基因主要通过质粒传播。通过分析 8592 个质粒序列数据库，我们确定这些质粒中的许多已经相互交换了基因，成为来自不同来源的基因的嵌合体。我们接下来根据它们分离的生物体将这些质粒分为不同的组，发现不同的组具有不同比例的镶嵌质粒。这一结果出乎意料，表明导致镶嵌质粒的机制和选择压力并非在所有物种中均匀发生。这也表明质粒可能为不同物种提供不同水平的潜在变异。这项工作揭示了原核生物中质粒的一种以前未被认识到的模式，这可能为我们深入了解质粒在进化中的作用提供新的见解。
