Microbial strain-level population structure and genetic diversity from metagenomes.
Microbial strain-level population structure and genetic diversity from metagenomes.
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DOI：
10.1101/gr.216242.116
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发表时间：
2017-04
期刊：
影响因子：
7
通讯作者：
Segata N
中科院分区：
文献类型：
--
作者：
Truong DT;Tett A;Pasolli E;Huttenhower C;Segata N
在与微生物群落相关的人类健康状况中，表型通常仅与致病微生物群中的一小部分菌株相关。尽管在微生物生理学中，几十年来对单个菌株进行表征一直是至关重要的，但在使用不依赖培养的高通量宏基因组学时，这一直是具有挑战性的。我们介绍了一种新的宏基因组菌株鉴定方法strain phlan，并应用它来表征来自北美和南美、欧洲、亚洲和非洲国家人群的1500多个肠道宏基因组中超过125个物种的数千个菌株的遗传结构。该方法依赖于物种特异性标记基因内的每样本显性序列变异重建。它主要确定了特定学科的菌株变异（<5%的学科间菌株共享），我们确定单个菌株通常主导每个物种，并随时间保留（约70%的物种）。微生物种群结构以几种不同的方式与宿主种群的地理结构相关。在某些情况下，离散的亚种（如直肠真杆菌和copri普雷沃氏菌）或连续的微生物遗传变异（如prausnitzii粪杆菌）与地理上不同的人群相关，而很少有菌株出现在多个不相关的队列中。我们进一步估计了肠道微生物的遗传变异性，拟杆菌种类表现出显著的一致性（菌株之间核苷酸变异的中位数为0.45%），而copri是最具可塑性的肠道定植菌之一。因此，我们在这里描述了以前无法进入的肠道微生物的群体遗传学，提供了肠道微生物多样性的全面菌株水平遗传概述。
Among the human health conditions linked to microbial communities, phenotypes are often associated with only a subset of strains within causal microbial groups. Although it has been critical for decades in microbial physiology to characterize individual strains, this has been challenging when using culture-independent high-throughput metagenomics. We introduce StrainPhlAn, a novel metagenomic strain identification approach, and apply it to characterize the genetic structure of thousands of strains from more than 125 species in more than 1500 gut metagenomes drawn from populations spanning North and South American, European, Asian, and African countries. The method relies on per-sample dominant sequence variant reconstruction within species-specific marker genes. It identified primarily subject-specific strain variants (<5% inter-subject strain sharing), and we determined that a single strain typically dominated each species and was retained over time (for >70% of species). Microbial population structure was correlated in several distinct ways with the geographic structure of the host population. In some cases, discrete subspecies (e.g., for Eubacterium rectale and Prevotella copri) or continuous microbial genetic variations (e.g., for Faecalibacterium prausnitzii) were associated with geographically distinct human populations, whereas few strains occurred in multiple unrelated cohorts. We further estimated the genetic variability of gut microbes, with Bacteroides species appearing remarkably consistent (0.45% median number of nucleotide variants between strains), whereas P. copri was among the most plastic gut colonizers. We thus characterize here the population genetics of previously inaccessible intestinal microbes, providing a comprehensive strain-level genetic overview of the gut microbial diversity.