Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

BACTERIAL PHYSIOLOGY

CRISPRs from scratch

Nature Microbiology volume 3, pages 261–262 (2018)Cite this article

Subjects

CRISPR immunity begins with the acquisition of sequences from invading nucleic acids through spacer integration into a CRISPR locus. Off-target integration of spacers into other parts of the genome is now implicated as a spontaneous source of new CRISPR loci.

The battle between phages and bacteria or archaea has persisted over cosmic timescales. Phages have evolved to propagate by injecting their genomes into a hijacked host cell, often killing it in the process. Bacteria and archaea have evolved several means to fight back, with clustered, regularly interspaced, short palindromic repeats (CRISPR) systems among the weapons in their molecular arsenal1. The short repeats within CRISPR sequences are interspaced by distinct bits of DNA called spacers. These spacers are usually taken from phages or other mobile genetic elements (MGEs) and integrated into the CRISPR array by two CRISPR-associated (Cas) proteins known as Cas1 and Cas2, sometimes with the assistance of additional factors, in a process known as adaptation2. The spacers are not just kept as mementos of survival, but instead serve as genetically encoded ‘memories’ of attack that enable specific defence against subsequent invasions. In this issue of Nature Microbiology3, Nivala et al. report that living bacterial cells occasionally mistake other parts of the genome for a leader-proximal CRISPR repeat and integrate a new spacer into the off-target location. Such integrations are sometimes lethal due to the disruption of essential genes, but when tolerated, this neo-CRISPR genesis pathway could spontaneously serve as a source of new CRISPR loci.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

Fig. 1: Canonical CRISPR adaptation versus neo-CRISPR genesis.

References

  1. Mohanraju, P. et al. Science 353, aad5147 (2016).

    Article  PubMed  Google Scholar 

  2. Jackson, S. A. et al. Science 356, eaal5056 (2017).

    Article  PubMed  Google Scholar 

  3. Nivala, J., Shipman, S. L. & Church, G. M. Nat. Microbiol. https://doi.org/10.1038/s41564-017-0097-z (2018).

  4. Nuñez, J. K., Bai, L., Harrington, L. B., Hinder, T. L. & Doudna, J. A. Mol. Cell 62, 824–833 (2016).

    Article  PubMed  Google Scholar 

  5. Shipman, S. L., Nivala, J., Macklis, J. D. & Church, G. M. Science 353, aaf1175 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Shipman, S. L., Nivala, J., Macklis, J. D. & Church, G. M. Nature 547, 345–349 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Nuñez, J. K., Harrington, L. B., Kranzusch, P. J., Engelman, A. N. & Doudna, J. A. Nature 519, 193–198 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Charpentier, E., Richter, H., van der Oost, J. & White, M. FEMS Microbiol. Rev. 39, 428–441 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA

    Alireza Edraki & Erik J. Sontheimer

  2. Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA

    Erik J. Sontheimer

Authors
  1. Alireza Edraki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Erik J. Sontheimer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Erik J. Sontheimer.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Edraki, A., Sontheimer, E.J. CRISPRs from scratch. Nat Microbiol 3, 261–262 (2018). https://doi.org/10.1038/s41564-018-0115-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41564-018-0115-9

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing