Metagenomics Leads to New CRISPR-Cas Systems

First CRISPR-Cas9 system in archaea discovered

The newly discovered CRISPR-CasY system was found in bacteria from deep underground at Crystal Geyser in California. (Jill Banfield, UC Berkeley)

The newly discovered CRISPR-CasY system was found in bacteria from deep underground at Crystal Geyser, a CO₂-driven geyser on the Colorado Plateau in Utah. (Jill Banfield, UC Berkeley)

The Science

Through metagenomic data generated by the DOE Joint Genome Institute, researchers analyzed 155 million protein coding genes from uncultivated microbial communities, leading to the discovery of the first CRISPR-Cas9 protein in the archaeal domain, and of two previously unknown simple bacterial CRISPR-Cas systems.

The Impact

Microbes play key roles in the planet’s cycles and characterizing them helps researchers work towards solutions for energy and environmental challenges. Examining environmental microbial communities has allowed access to an unprecedented diversity of genomes and CRISPR-Cas systems that have many applications, including biological research. Using the combined computational-experimental approach that was successful in this study, nearly all environments where life exists can be investigated.

Summary

Microbes heavily influence our planet’s cycles, but only a fraction has been identified. Characterizing the abundant and unknown microbial diversity can help researchers develop solutions to energy and environmental challenges. In microbes, CRISPR-Cas systems grant adaptive immunity, and these gene-editing tools are the bases of versatile technologies revolutionizing research. Thus far, CRISPR-Cas technology has been based only on systems from isolated bacteria. In a study led by longtime DOE JGI collaborator Jill Banfield of UC Berkeley, researchers report discovering for the first time, a CRISPR-Cas9 system in archaea, as well as of simple CRISPR-Cas systems in uncultivable bacteria. To identify these new CRISPR-Cas systems, Banfield and her colleagues harnessed more than a decade’s worth of metagenomic data from samples sequenced and analyzed by the U.S. Department of Energy Joint Genome Institute (DOE JGI), a DOE Office of Science User Facility. The CasX and CasY proteins were found in bacteria from groundwater and sediment samples. The archaeal Cas9 were identified in samples taken from the Iron Mountain Superfund site as part of Banfield’s pioneering metagenomics work with the DOE JGI. Both CasX and CasY are among some of the most compact systems ever identified. Banfield’s team noted that this application of metagenomics gives a huge validation to studies of CRISPR-Cas proteins using living organisms. The study was published ahead in Nature on December 16, 2016.

Contacts

Daniel Drell, Ph.D.
Program Manager
Biological Systems Sciences Division
Office of Biological and Environmental Research
Office of Science
US Department of Energy
[email protected]

Jill Banfield
UC Berkeley
[email protected]

Funding

DOE Office of Science
National Science Foundation
EMBO
German Science Foundation
Paul Allen Institute
Howard Hughes Medical Institute

Publications

Burstein D et al. New CRISPR–Cas systems from uncultivated microbes. Nature. 2016 Dec 22. doi: 10.1038/nature21059. [Epub ahead of print]