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New CRISPR-Cas, Gene Editing Systems, Discovered in Vast DNA Sequence Dataset

Researchers discover the first CRISPR-Cas9 system in archaea, which may enable new technologies for biological research

by U.S. Department of Energy
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An artistic representation of the Tree of LifeAn artistic representation of the Tree of Life, with the many groups of bacteria on the left, the unknown bacteria at upper right (purple), and the archaea and eukaryotes—which include humans—at the lower right.Image credit: Artistic representation of Fig. 1 from Hug et al., “A new view of the tree of life.” Nature Microbiology 1 (2016). [DOI: 10.1038/nmicrobiol.2016.48] Courtesy of Jill Banfield, University of California, Berkeley

The Science

Knowing the extent of microbial diversity, especially gene editing, can help scientists solve energy and cleanup challenges. Using large amounts of genetic data, researchers analyzed 155 million protein-coding genes from uncultivated microbial communities. This work led to the discovery of the first CRISPR- (clustered regularly interspaced short palindromic repeats) Cas9 protein in the archaeal domain, a sister group to bacteria. The team also found two previously unknown simple bacterial CRISPR-Cas systems. A CRISPR-Cas system uses Cas proteins to edit the microbial DNA. The CRISPR-Cas system is the basis of technologies revolutionizing research. Until this study, scientists only knew of CRISPR-Cas systems in a few isolated bacteria, not the single-celled archaea; this finding suggests that CRISPR-Cas editing systems may be much more widespread in nature than previously believed.

The Impact

Microbes play key roles in the planet’s cycles. Characterizing microbes helps researchers work toward solutions for energy and environmental challenges. Examining environmental microbial communities has enabled access to an unprecedented diversity of genomes and CRISPR-Cas systems. The systems have applications including biological research. The combined computational-experimental approach that was successful in this study can be used to investigate nearly all environments where life exists.

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Microbes heavily influence the planet’s cycles, but only a fraction have been identified. Characterizing the abundant but largely unknown extent of microbial diversity can help researchers develop solutions to energy and environmental challenges. In microbes, CRISPR-Cas systems provide a form of adaptive immunity, and these gene-editing tools are the foundation of versatile technologies revolutionizing research. Thus far, CRISPR-Cas technology has been based only on systems from isolated bacteria. In a study published February 9 in Nature and led by Jill Banfield of the University of California, Berkeley, researchers discovered, for the first time, a CRISPR-Cas9 system in archaea. They also discovered simple CRISPR-Cas systems in uncultivable bacteria. To identify these new CRISPR-Cas systems, the team harnessed more than a decade’s worth of metagenomic data from samples sequenced and analyzed by the U.S. Department of Energy’s Joint Genome Institute (DOE JGI), a DOE Office of Science user facility. The team found the CasX and CasY proteins in bacteria from groundwater and sediment samples. The archaeal Cas9 was identified in samples taken from the Iron Mountain Superfund site as part of Banfield’s pioneering metagenomics work with DOE JGI. Both CasX and CasY are among some of the most compact systems ever identified. This application of metagenomics validates studies of CRISPR-Cas proteins using living organisms.