MetaGenomic Species (MGS:530) from Distal Human Gut Microbiota (MetaHit), Sample MH0006. Bacteroides sp. CAG:530

Metagenomic data acquired by deep sequencing is immensely complex, lacks apparent structure and is typically dominated by unknown species. Using an abundance co-variance strategy, we group highly co-varying genes into MetaGenomic Species, which represent a wide range of biological entities: bacterial genomes, plasmids, genomic islands, clonal variation and bacteriophages. Applying this concept to a new 3.9 million microbial gene catalogue derived from 396 human stool samples we identified 7,381 such MetaGenomic Species. They range in size from 3 to 6,319 genes, with 741 MetaGenomic Species resembling bacterial genomes in number of genes contained. The Meta-Genomic Species displays remarkable consistency in taxonomy and GC content. 247 of the MetaGenomic Species assemblies even pass the HMP high quality draft genome criteria. A large proportion (73%) of the MetaGenomic Species displays no sequence similarity to any previously sequenced organism. Smaller MetaGenomic Species are enriched for genes characteristic for bacteriophages and functions important for biotic interactions and show strong dependencies to gene-rich MetaGenomic Species. We present the first unsupervised structuring of a highly complex series of metagenomic samples into biological entities, including a global analysis of the genetic interdependencies between bacteria, plasmids, phages and genetic islands in the human distal gut.

通过深度测序获取的宏基因组数据（Metagenomic data）极为复杂，缺乏明显的结构特征，且通常以未知物种为主。本研究采用丰度共变异策略，将高度共变异的基因归类为宏基因组物种（MetaGenomic Species），这类物种涵盖了多种生物实体：细菌基因组、质粒、基因组岛、克隆变异以及噬菌体。我们将这一概念应用于由396份人类粪便样本构建的全新390万微生物基因目录中，共鉴定出7381个此类宏基因组物种。其基因数量介于3至6319之间，其中741个宏基因组物种所含基因数与细菌基因组规模相当。该类宏基因组物种在分类学特征与GC含量上表现出显著的一致性。其中247个宏基因组物种的组装结果甚至满足人类微生物组计划（HMP）高质量草图基因组标准。73%的宏基因组物种与任何已测序生物均无序列相似性。小型宏基因组物种显著富集噬菌体特征基因及参与生物互作的关键功能基因，且与基因丰富度较高的宏基因组物种存在较强的依赖关系。本研究首次实现了将高度复杂的宏基因组样本集无监督结构化划分为生物实体，并对人类远端肠道内细菌、质粒、噬菌体及基因组岛之间的遗传互作关系进行了全局性分析。