CRISPR-Cas systems target a diverse collection of invasive mobile genetic elements in human microbiomes

被引:40
|
作者
Zhang, Quan [1 ]
Rho, Mina [2 ]
Tang, Haixu [1 ,3 ]
Doak, Thomas G. [4 ]
Ye, Yuzhen [1 ]
机构
[1] Indiana Univ, Sch Informat & Comp, Bloomington, IN 47405 USA
[2] Roswell Pk Canc Inst, Dept Biostat & Bioinformat, Buffalo, NY 14263 USA
[3] Indiana Univ, Sch Informat & Comp, Ctr Genom & Bioinformat, Bloomington, IN 47405 USA
[4] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA
来源
GENOME BIOLOGY | 2013年 / 14卷 / 04期
基金
美国国家科学基金会;
关键词
CRISPR-Cas system; human microbiome; mobile genetic element (MGE); PROVIDES ACQUIRED-RESISTANCE; GENOMIC ISLANDS; IMMUNE-SYSTEM; RNA; BACTERIA; SEQUENCE; IDENTIFICATION; INTERFERENCE; PREDICTION; DATABASE;
D O I
10.1186/gb-2013-14-4-r40
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Background: Bacteria and archaea develop immunity against invading genomes by incorporating pieces of the invaders' sequences, called spacers, into a clustered regularly interspaced short palindromic repeats (CRISPR) locus between repeats, forming arrays of repeat-spacer units. When spacers are expressed, they direct CRISPR-associated (Cas) proteins to silence complementary invading DNA. In order to characterize the invaders of human microbiomes, we use spacers from CRISPR arrays that we had previously assembled from shotgun metagenomic datasets, and identify contigs that contain these spacers' targets. Results: We discover 95,000 contigs that are putative invasive mobile genetic elements, some targeted by hundreds of CRISPR spacers. We find that oral sites in healthy human populations have a much greater variety of mobile genetic elements than stool samples. Mobile genetic elements carry genes encoding diverse functions: only 7% of the mobile genetic elements are similar to known phages or plasmids, although a much greater proportion contain phage-or plasmid-related genes. A small number of contigs share similarity with known integrative and conjugative elements, providing the first examples of CRISPR defenses against this class of element. We provide detailed analyses of a few large mobile genetic elements of various types, and a relative abundance analysis of mobile genetic elements and putative hosts, exploring the dynamic activities of mobile genetic elements in human microbiomes. A joint analysis of mobile genetic elements and CRISPRs shows that protospacer-adjacent motifs drive their interaction network; however, some CRISPR-Cas systems target mobile genetic elements lacking motifs. Conclusions: We identify a large collection of invasive mobile genetic elements in human microbiomes, an important resource for further study of the interaction between the CRISPR-Cas immune system and invaders.
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页数:15
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