An updated evolutionary classification of CRISPR–Cas systems including rare variants

Executive Insight

CRISPR-Cas systems are bacterial immune systems against viruses from which specific components could be successfully diverted into powerful genetic engineering tools with considerable applications in agriculture, medicine, and biotechnology.
Today, thanks to accumulating genomic and metagenomic sequences, the known diversity of CRISPR-Cas systems is widely used and continues to expand. This expanding diversity requires regular updates to CRISPR-Cas nomenclature and classification. The last are two fundamental considerations that, nevertheless, are critical to the large scientific community leveraging CRISPR-Cas-based tools.

Building on a foundational article from 2011 and two updates in 2015 and 2020, this latest update describes 2 classes 7 types and 46 subtypes of CRISPR-Cas systems. The study shows that the previously defined systems are relatively common, whereas newly characterized variants are comparatively rare.

Why This Research Matters

IFF has played a leading role in CRISPR-Cas research since publishing a groundbreaking study in Science in 2007. Since then, IFF scientists have contributed to numerous high-impact publications that have advanced the field.

Considered to be “the discovery of the century” in modern biology, CRISPR-Cas research was recognized with the Nobel Prize in Chemistry in 2020.

These series of articles treating CRISPR-Cas nomenclature and classification rank among the most cited publications in the field. Through its contributions to this work, IFF continues to strengthen its scientific reputation, visibility, and research network.

About the Authors

Dr. Kira Makarova and Dr. Eugene Koonin of the National Center for Biotechnology Information (National Library of Medicine, National Institutes of Health, Bethesda, MD, USA) led this study, as well as the three previous classification updates.

Since 2011, they have brought together leading experts to establish and refine the CRISPR-Cas classification framework. Among the selected contributors is Philippe Horvath, Senior Lead Scientist and Technical Fellow at IFF, whose pioneering research helped shape the CRISPR field.

Expert Contributor: Philippe Horvath, Senior Lead Scientist and Technical Fellow at IFF.

Practical Applications

This work provides the scientific community with a common language (nomenclature of cas genes, for instance) and a robust classification framework for CRISPR-Cas systems.

The identification of novel CRISPR-Cas systems also creates opportunities to develop improved gene editing tools that will undoubtedly contribute to designing better microbes, vegetables and animals used in various food applications.

How This Research Was Conducted

A core team of three to six researchers analyzed conducted the data research in silico and wrote the initial version of the article including the figures. The project ultimately involved 29 co-authors that substantially contributed to the discussion of the content, edition and approval of the manuscript.

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