Nimkulrat Sutichot, Lee Heewook, Doak Thomas G, Ye Yuzhen
School of Informatics and Computing, Indiana University, Bloomington IN, USA.
Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh PA, USA.
Front Microbiol. 2016 Jun 3;7:852. doi: 10.3389/fmicb.2016.00852. eCollection 2016.
Diversity-generating retroelements (DGRs) are genetic cassettes that can produce massive protein sequence variation in prokaryotes. Presumably DGRs confer selective advantages to their hosts (bacteria or viruses) by generating variants of target genes-typically resulting in target proteins with altered ligand-binding specificity-through a specialized error-prone reverse transcription process. The only extensively studied DGR system is from the Bordetella phage BPP-1, although DGRs are predicted to exist in other species. Using bioinformatics analysis, we discovered that the DGR system associated with the Treponema denticola species (a human oral-associated periopathogen) is dynamic (with gains/losses of the system found in the isolates) and diverse (with multiple types found in isolated genomes and the human microbiota). The T. denticola DGR is found in only nine of the 17 sequenced T. denticola strains. Analysis of the DGR-associated template regions and reverse transcriptase gene sequences revealed two types of DGR systems in T. denticola: the ATCC35405-type shared by seven isolates including ATCC35405; and the SP32-type shared by two isolates (SP32 and SP33), suggesting multiple DGR acquisitions. We detected additional variants of the T. denticola DGR systems in the human microbiomes, and found that the SP32-type DGR is more abundant than the ATCC35405-type in the healthy human oral microbiome, although the latter is found in more sequenced isolates. This is the first comprehensive study to characterize the DGRs associated with T. denticola in individual genomes as well as human microbiomes, demonstrating the importance of utilizing both individual genomes and metagenomes for characterizing the elements, and for analyzing their diversity and distribution in human populations.
多样性产生反转录元件（DGRs）是一种基因盒，能够在原核生物中产生大量蛋白质序列变异。据推测，DGRs通过一种特殊的易出错逆转录过程产生靶基因变体，从而赋予其宿主（细菌或病毒）选择优势，这通常会导致靶蛋白的配体结合特异性发生改变。唯一得到广泛研究的DGR系统来自博德特氏菌噬菌体BPP-1，不过预计其他物种中也存在DGRs。通过生物信息学分析，我们发现与齿垢密螺旋体（一种与人类口腔相关的牙周病原体）相关的DGR系统具有动态性（在分离株中发现该系统有获得/缺失情况）和多样性（在分离基因组和人类微生物群中发现多种类型）。在17株已测序的齿垢密螺旋体菌株中，只有9株含有齿垢密螺旋体DGR。对与DGR相关的模板区域和逆转录酶基因序列的分析揭示了齿垢密螺旋体中的两种DGR系统：包括ATCC35405在内的7个分离株共有的ATCC35405型；以及由两个分离株（SP32和SP33）共有的SP32型，这表明存在多次DGR获得事件。我们在人类微生物群中检测到了齿垢密螺旋体DGR系统的其他变体，并且发现，在健康人类口腔微生物群中，SP32型DGR比ATCC35405型更为丰富，尽管后者在更多已测序的分离株中出现。这是首次对个体基因组以及人类微生物群中与齿垢密螺旋体相关的DGRs进行全面表征的研究，证明了利用个体基因组和宏基因组来表征这些元件以及分析它们在人群中的多样性和分布的重要性。
