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CRISPR–Cas in mobile genetic elements: counter-defence and beyond

Nature Reviews Microbiology volume 17, pages 513–525 (2019)Cite this article

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Abstract

The principal function of CRISPR–Cas systems in archaea and bacteria is defence against mobile genetic elements (MGEs), including viruses, plasmids and transposons. However, the relationships between CRISPR–Cas and MGEs are far more complex. Several classes of MGE contributed to the origin and evolution of CRISPR–Cas, and, conversely, CRISPR–Cas systems and their components were recruited by various MGEs for functions that remain largely uncharacterized. In this Analysis article, we investigate and substantially expand the range of CRISPR–Cas components carried by MGEs. Three groups of Tn7-like transposable elements encode ‘minimal’ type I CRISPR–Cas derivatives capable of target recognition but not cleavage, and another group encodes an inactivated type V variant. These partially inactivated CRISPR–Cas variants might mediate guide RNA-dependent integration of the respective transposons. Numerous plasmids and some prophages encode type IV systems, with similar predicted properties, that appear to contribute to competition among plasmids and between plasmids and viruses. Many prokaryotic viruses also carry CRISPR mini-arrays, some of which recognize other viruses and are implicated in inter-virus conflicts, and solitary repeat units, which could inhibit host CRISPR–Cas systems.

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Fig. 1: Evolutionary relationships and gene fluxes between CRISPR–Cas systems and mobile genetic elements.
Fig. 2: Derived type I CRISPR–Cas systems in Tn7-like transposons.
Fig. 3: Type IV CRISPR–Cas systems in plasmids and prophages.
Fig. 4: Origins of spacers in CRISPR arrays from viruses and proviruses.
Fig. 5: CRISPR mini-arrays in Streptococcus thermophilus lytic bacteriophages.
Fig. 6: Proposed functions and mechanisms of virus-encoded CRISPR mini-arrays and solitary repeat units.

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Acknowledgements

G.F., S.A.S., K.S.M. and E.V.K. are supported by funds from the Intramural Research Program of the National Institutes of Health of the USA. S.A.S. was additionally supported by the Russian Foundation for Basic Research (research project 18-34-00012) and a systems biology fellowship from Philip Morris Sales and Marketing. J.E.P. was supported by the US Department of Agriculture National Institute of Food and Agriculture Hatch Project NYC-189438. D.R.C., W.X.Y. and D.A.S. are supported by Arbor Biotechnologies.

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Nature Reviews Microbiology thanks U. Gophna, and other anonymous reviewer(s), for their contribution to the peer review of this work.

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Authors and Affiliations

  1. National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA

    Guilhem Faure, Sergey A. Shmakov, Kira S. Makarova & Eugene V. Koonin

  2. Broad Institute of MIT and Harvard, Cambridge, MA, USA

    Guilhem Faure

  3. Skolkovo Institute of Science and Technology, Skolkovo, Russia

    Sergey A. Shmakov

  4. Arbor Biotechnologies, Cambridge, MA, USA

    Winston X. Yan, David R. Cheng & David A. Scott

  5. Department of Microbiology, Cornell University, Ithaca, NY, USA

    Joseph E. Peters

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Contributions

G.F., S.A.S., W.X.Y., D.R.C., D.A.S., J.E.P., K.S.M. and E.V.K. researched the data for the article. G.F., W.X.Y., D.R.C., D.A.S., J.E.P., K.S.M. and E.V.K. substantially contributed to the discussion of the content. E.V.K. wrote the article. G.F., W.X.Y., D.R.C., D.A.S., J.E.P., K.S.M. and E.V.K. reviewed and edited the manuscript before submission.

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Correspondence to Eugene V. Koonin.

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Glossary

CRISPR spacers

Unique sequences of 20–60 nucleotides inserted between the repeats in the CRISPR array and employed, as part of the CRISPR RNA, for targeting DNA molecules containing a homologous protospacer.

CRISPR array

A series of direct repeats in bacterial and archaeal genomes interspersed with spacers that are acquired primarily from mobile genetic element DNA.

crRNAs

Short RNAs, produced by processing of the primary transcript of a CRISPR array, that consists of a spacer and portions of the flanking repeats and functions as a guide to target DNA or RNA molecules containing cognate protospacers.

Mini-arrays

Minimal forms of a CRISPR array that consists of a proximal repeat, a spacer and a distal repeat, or, more commonly, a partial repeat; so far identified in virus and provirus genomes.

Solitary repeat units

(SRUs). Short sequences, so far identified in virus and provirus genomes, that are (nearly) identical to a repeat from a CRISPR array.

CRISPR adaptation module

A group of cas genes dedicated to the selection and insertion of new spacers into CRISPR arrays.

TnpB

A nuclease containing a RuvC-like domain that is encoded by numerous transposons (insertion sequences) although not required for transposition.

IS605-like transposons

A family of bacterial and archaeal insertion sequence elements that encode a distinct transposase (TnpA) and often a second nuclease (TnpB) that is also found in numerous non-autonomous IS605-like transposons lacking TnpA.

Tn7-like transposons

A derivative of Tn7 family transposons lacking some accessory genes involved in transposition and in some cases carrying derived CRISPR–Cas systems lacking the interference capacity.

CRISPR effector module

A suite of Cas proteins (Class 1 CRISPR–Cas systems) or a single large protein (Class 2 CRISPR–Cas systems) that are responsible for maturation of the CRISPR RNA and interference.

R-loops

Three-stranded structures that consist of a DNA–RNA hybrid and the displaced single-stranded DNA, formed during transcription and other processes including target recognition by CRISPR–Cas effector complexes (proteins).

Protospacer

A piece of DNA, typically from a mobile genetic element genome, that is inserted into a CRISPR array by the CRISPR adaptation complex, to become a spacer.

CysH enzymes

Enzymes of the adenosine 5′-phosphosulfate reductase family that reduce activated sulfate to sulfite; associated with many type IV CRISPR–Cas systems.

Exaptation

Co-option (recruitment) of a biological entity, such as a protein or DNA sequence, for a role that is distinct from its original function.

Anti-CRISPR proteins

Diverse proteins encoded by many bacterial and archaeal viruses that inhibit the host CRISPR–Cas systems, typically by binding and inactivating the effector complex (protein).

Transactivating RNAs

(tracrRNAs). RNA molecules encoded by all known type II CRISPR–Cas systems and some type V systems that consist of a sequence partially complementary to the corresponding repeat and a unique portion; co-folding of the tracrRNA with the pre-crRNA is essential for crRNA maturation and interference by the respective CRISPR–Cas systems.

Protospacer adjacent motif

(PAM). A short, two-to-three-nucleotide motif, the presence of which next to the protospacer sequence is essential for both adaptation and interference by most of the CRISPR–Cas systems; different PAM sequences are required by different CRISPR-Cas types and subtypes.

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Faure, G., Shmakov, S.A., Yan, W.X. et al. CRISPR–Cas in mobile genetic elements: counter-defence and beyond. Nat Rev Microbiol 17, 513–525 (2019). https://doi.org/10.1038/s41579-019-0204-7

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