MetaGenomic Species (MGS:230) from Distal Human Gut Microbiota (MetaHit), Sample V1.UC55-4. Clostridium sp. CAG:230

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极为复杂，缺乏明确的结构特征，且通常以未知物种为主要构成部分。我们采用丰度共变异策略，将高度共变异的基因聚类为宏基因组物种（MetaGenomic Species），这类实体涵盖了多种生物组分：细菌基因组、质粒、基因组岛、克隆变异体以及噬菌体。将这一思路应用于由396份人类粪便样本构建的全新390万微生物基因集，我们共鉴定出7381个此类宏基因组物种。这些宏基因组物种包含的基因数从3个至6319个不等，其中741个宏基因组物种的基因数量与细菌基因组规模相近。此类宏基因组物种在分类学与GC含量上均呈现出显著的一致性。其中247个宏基因组物种的组装结果甚至达到了人类微生物组计划（Human Microbiome Project，HMP）制定的高质量草图基因组标准。73%的宏基因组物种与已测序的任何生物体均未检测到序列相似性。基因数量较少的宏基因组物种显著富集噬菌体特征基因以及与生物相互作用相关的功能基因，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。本研究首次采用无监督方法，将一系列高度复杂的宏基因组样本划分为明确的生物实体，并针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开展了系统性全局分析。