Comparative metagenomic analysis of plasmid encoded functions in the human gut microbiome.

Comparative metagenomic analysis of plasmid encoded functions in the human gut microbiome.
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DOI:
10.1186/1471-2164-11-46
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发表时间:
2010-01-19
期刊:
影响因子:
4.4
通讯作者:
Marchesi JR
Marchesi JR
中科院分区:
生物学2区
文献类型:
--
作者:
Jones BV;Sun F;Marchesi JR

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关于与人类肠道微生物组相关的可移动遗传元素池,我们所知甚少。在这项研究中,我们采用培养独立的TRACA系统从人类肠道微生物群中分离出新的质粒,并通过比较宏基因组分析来研究这些质粒编码的功能在人类肠道微生物群中的分布和相对丰度。从人类肠道微生物组中获得了新的质粒,并在本文分析的多个人类肠道微生物组中鉴定出与两个质粒(pTRACA10和pTRACA22)具有高一致性(>90%)的同源核苷酸序列。然而,在小鼠肠道或环境宏基因组中没有发现与这些质粒同源的核苷酸序列。与来自其他环境的微生物群落相比,由质粒pTRACA10和pTRACA22编码的功能在人类肠道微生物组中更为普遍。其中发现的最普遍的功能是推测的RelBE毒素-抗毒素(TA)依赖模块,随后的分析显示,这与推测的来自厚壁菌门肠道相关细菌的TA模块最密切相关。RelE毒素基因在肠道相关菌种(厚壁菌门、拟杆菌门、放线菌门和变形菌门)中具有广泛的系统发育分布,但在肠道相关古细菌种中未发现RelE同源基因。我们还提供了间接证据,证明这些基因在属于不同系统发育分裂的细菌物种之间的水平转移,即革兰氏阴性变形菌门和革兰氏阳性物种来自厚壁菌门。应用培养独立系统从人类肠道移动宏基因组中捕获新的质粒,再加上随后的宏基因组比较分析,突出了质粒编码功能在肠道微生物生态系统中的意外流行。特别是增加的相对丰度和广泛的系统发育分布被确定为推定的RelBE毒素/抗毒素成瘾模块,推定的磷酸水解酶/磷酸酯酶和功能未知的ORF。我们的分析还表明,一些质粒或质粒家族存在于地理上孤立的人类宿主的肠道微生物组中,这些宿主具有广泛的全球分布(美国、日本和欧洲),并且可能是人类肠道微生物组所独有的。对与人类肠道相关的质粒群体的进一步研究可能为人类肠道微生物群的发育、功能和进化提供重要的见解。
Little is known regarding the pool of mobile genetic elements associated with the human gut microbiome. In this study we employed the culture independent TRACA system to isolate novel plasmids from the human gut microbiota, and a comparative metagenomic analysis to investigate the distribution and relative abundance of functions encoded by these plasmids in the human gut microbiome. Novel plasmids were acquired from the human gut microbiome, and homologous nucleotide sequences with high identity (>90%) to two plasmids (pTRACA10 and pTRACA22) were identified in the multiple human gut microbiomes analysed here. However, no homologous nucleotide sequences to these plasmids were identified in the murine gut or environmental metagenomes. Functions encoded by the plasmids pTRACA10 and pTRACA22 were found to be more prevalent in the human gut microbiome when compared to microbial communities from other environments. Among the most prevalent functions identified was a putative RelBE toxin-antitoxin (TA) addiction module, and subsequent analysis revealed that this was most closely related to putative TA modules from gut associated bacteria belonging to the Firmicutes. A broad phylogenetic distribution of RelE toxin genes was observed in gut associated bacterial species (Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria), but no RelE homologues were identified in gut associated archaeal species. We also provide indirect evidence for the horizontal transfer of these genes between bacterial species belonging to disparate phylogenetic divisions, namely Gram negative Proteobacteria and Gram positive species from the Firmicutes division. The application of a culture independent system to capture novel plasmids from the human gut mobile metagenome, coupled with subsequent comparative metagenomic analysis, highlighted the unexpected prevalence of plasmid encoded functions in the gut microbial ecosystem. In particular the increased relative abundance and broad phylogenetic distribution was identified for a putative RelBE toxin/antitoxin addiction module, a putative phosphohydrolase/phosphoesterase, and an ORF of unknown function. Our analysis also indicates that some plasmids or plasmid families are present in the gut microbiomes of geographically isolated human hosts with a broad global distribution (America, Japan and Europe), and are potentially unique to the human gut microbiome. Further investigation of the plasmid population associated with the human gut is likely to provide important insights into the development, functioning and evolution of the human gut microbiota.
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