Novel genomic island modifies DNA with 7-deazaguanine derivatives

Novel genomic island modifies DNA with 7-deazaguanine derivatives
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DOI:
10.1073/pnas.1518570113
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发表时间:
2016-03-15
影响因子:
11.1
通讯作者:
de Crecy-Lagard, Valerie
de Crecy-Lagard, Valerie
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Thiaville, Jennifer J.;Kellner, Stefanie M.;de Crecy-Lagard, Valerie

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类似 20 kb 的基因簇的发现,包含 tRNA 鸟苷转糖基酶基因的旁系同源家族(称为 tgtA5),以及 7-氰基-7-去氮鸟嘌呤 (preQ(0)) 合成和 DNA 代谢基因,导致了 7-去氮鸟嘌呤衍生物插入 DNA 的假设。这是通过检测从致病性革兰氏阴性细菌蒙得维的亚肠沙门氏菌提取的 DNA 的酶解产物中检测 2'-脱氧-preQ(0) 和 2'-脱氧-7-酰胺-7-脱氮鸟苷而确定的。这些修饰在密切相关的鼠伤寒沙门氏菌血清变种 LT2 和蒙得维的亚沙门氏菌突变体中不存在,它们都缺乏基因簇。这导致我们将 S. Montevideo 簇的基因重命名为 dpdA-K,代表 DNA 中的 7-脱氮嘌呤。对 150 种系统发育不同的细菌进行了类似的基因簇分析,并在含有这些簇的其他生物体的 DNA 中检测到了这些修饰,包括耐放射动球菌、睾丸酮丛毛单胞菌和阿拉斯肯鞘氨醇菌。比较基因组分析表明,在肠杆菌科细菌中,该簇是整合在 leuX 位点上的基因组岛,TgtA5 家族的系统发育分析与广泛的水平基因转移一致。修饰或未修饰质粒转化为含有或缺乏该簇的同基因蒙得维的亚沙门氏菌菌株的转化效率的比较强烈表明该簇在肠杆菌科中的限制性修饰作用。另一种 preQ(0) 衍生物,2'-脱氧-7-甲脒基-7-脱氮鸟苷,在大肠杆菌噬菌体 9g 中被发现,正如根据参与古氨酸 tRNA 修饰合成的基因同源物的存在所预测的那样。这些结果说明了 DNA 和 tRNA 代谢之间深刻且意想不到的进化联系。
The discovery of similar to 20-kb gene clusters containing a family of paralogs of tRNA guanosine transglycosylase genes, called tgtA5, alongside 7-cyano-7-deazaguanine (preQ(0)) synthesis and DNA metabolism genes, led to the hypothesis that 7-deazaguanine derivatives are inserted in DNA. This was established by detecting 2'-deoxy-preQ(0) and 2'-deoxy-7-amido-7-deazaguanosine in enzymatic hydrolysates of DNA extracted from the pathogenic, Gram-negative bacteria Salmonella enterica serovar Montevideo. These modifications were absent in the closely related S. enterica serovar Typhimurium LT2 and from a mutant of S. Montevideo, each lacking the gene cluster. This led us to rename the genes of the S. Montevideo cluster as dpdA-K for 7-deazapurine in DNA. Similar gene clusters were analyzed in similar to 150 phylogenetically diverse bacteria, and the modifications were detected in DNA from other organisms containing these clusters, including Kineococcus radiotolerans, Comamonas testosteroni, and Sphingopyxis alaskensis. Comparative genomic analysis shows that, in Enterobacteriaceae, the cluster is a genomic island integrated at the leuX locus, and the phylogenetic analysis of the TgtA5 family is consistent with widespread horizontal gene transfer. Comparison of transformation efficiencies of modified or unmodified plasmids into isogenic S. Montevideo strains containing or lacking the cluster strongly suggests a restriction-modification role for the cluster in Enterobacteriaceae. Another preQ(0) derivative, 2'-deoxy-7-formamidino-7-deazaguanosine, was found in the Escherichia coli bacteriophage 9g, as predicted from the presence of homologs of genes involved in the synthesis of the archaeosine tRNA modification. These results illustrate a deep and unexpected evolutionary connection between DNA and tRNA metabolism.