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

Genome Biology

Yuzhen Ye¹  Thomas G Doak³  Haixu Tang²  Mina Rho⁴  Quan Zhang¹ 

[1] School of Informatics and Computing, Indiana University, 150 South Woodlawn Avenue, Bloomington, IN 47405, USA;Center for Genomics and Bioinformatics, School of Informatics and Computing, Indiana University, 150 South Woodlawn Avenue, Bloomington, IN 47405, USA;Department of Biology, Indiana University, 1001 East Third Street, Bloomington, IN 47405, USA;Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263, USA

关键词: mobile genetic element (MGE);    human microbiome;    CRISPR-Cas system;   

Others  :  866858
DOI  :  10.1186/gb-2013-14-4-r40

 received in 2013-02-07, accepted in 2013-04-29,  发布年份 2013

【 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.

【 授权许可】

   
2013 Zhang et al.; licensee BioMed Central Ltd.

【 图 表 】

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