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Engineered reproductively isolated species drive reversible population replacement

Buchman, Anna and Shriner, Isaiah and Yang, Ting and Liu, Junru and Antoshechkin, Igor and Marshall, John M. and Perry, Michael W. and Akbari, Omar S. (2021) Engineered reproductively isolated species drive reversible population replacement. Nature Communications, 12 . Art. No. 3281. ISSN 2041-1723. doi:10.1038/s41467-021-23531-z.

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Engineered reproductive species barriers are useful for impeding gene flow and driving desirable genes into wild populations in a reversible threshold-dependent manner. However, methods to generate synthetic barriers are lacking in advanced eukaryotes. Here, to overcome this challenge, we engineer SPECIES (Synthetic Postzygotic barriers Exploiting CRISPR-based Incompatibilities for Engineering Species), an engineered genetic incompatibility approach, to generate postzygotic reproductive barriers. Using this approach, we create multiple reproductively isolated SPECIES and demonstrate their reproductive isolation and threshold-dependent gene drive capabilities in D. melanogaster. Given the near-universal functionality of CRISPR tools, this approach should be portable to many species, including insect disease vectors in which confinable gene drives could be of great practical utility.

Item Type:Article
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URLURL TypeDescription Paper ItemData ItemData ItemData ItemData ItemData ItemData ItemData ItemData ItemData ItemData ItemData ItemData ItemData ItemData ItemCode
Buchman, Anna0000-0002-8775-6147
Shriner, Isaiah0000-0002-5897-8250
Yang, Ting0000-0001-7201-4231
Antoshechkin, Igor0000-0002-9934-3040
Marshall, John M.0000-0003-0603-7341
Perry, Michael W.0000-0002-5977-8031
Akbari, Omar S.0000-0002-6853-9884
Additional Information:© The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit Received 22 October 2020; Accepted 23 April 2021; Published 02 June 2021. We thank V. Kumar for help with library preparations. Sequencing was performed at the Millard and Muriel Jacobs Genetics and Genomics Laboratory at the California Institute of Technology. We thank N. Windbichler for sharing published sgRNA lines. We also thank Dr. N. Perrimon and B. Ewen-Campen for sharing published sgRNA-expressing flies and plasmids. We thank J. Reinitz for sharing antibodies. This work was supported in part by funding from UCSD lab startup funds awarded to O.S.A. and a DARPA Safe Genes Program Grant (HR0011-17-2-0047) awarded to O.S.A. and J.M.M. Data availability: The RNA sequencing data generated in this study is available at NCBI SRA under accession number PRJNA578541. All plasmids and annotated DNA sequence maps are available at under accession numbers; 112686; 124999; 125000; 125001; 125002; 125003; 125004; 125005; 125006; 125007. The fly strains engineered in this study and used to generate SPECIES A1 will be available at the Bloomington fly stock center with the stock numbers 79005, 91792, 91791. SPECIES fly lines will be made available from the corresponding author upon reasonable request upon agreement to suggested guidelines for the laboratory confinement of gene drive systems13,43. Source data are provided with this paper. Code availability: Code used to analyze drive experiment data and generate Figs. 4–6 is available on GitHub at and Zenodo at Author Contributions: O.S.A. conceptualized the study. A.B, I.S., T.Y., J.L., I.A., J.M.M., and M.W.P. performed various genetic, molecular experiments, immunohistochemistry, bioinformatic, and mathematical modeling described in the study. All authors contributed to writing, analyzed the data, and approved the final manuscript. Competing interests: O.S.A. and A.B. have a patent pending on this technology. Patent applicant—University of California, UCSD. Name of inventor(s)—A.B. and O.S.A. Application number—Invention 2020-184. Status of application—Pending. Specific aspect of manuscript covered in patent application—Using multiplexed dCas9/Cas9/gRNA combinations to generate reproductive isolation that can be used for population control. O.S.A. is co-founder and serves on the scientific advisory board of Agragene. All other authors declare no significant competing financial, professional, or personal interests that might have influenced the performance or presentation of the work described. Peer review information: Nature Communications thanks Gus McFarlane and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
Group:Millard and Muriel Jacobs Genetics and Genomics Laboratory
Funding AgencyGrant Number
University of California, San DiegoUNSPECIFIED
Defense Advanced Research Projects Agency (DARPA)HR0011-17-2-0047
Subject Keywords:CRISPR-Cas9 genome editing; Evolutionary biology; Synthetic biology
Record Number:CaltechAUTHORS:20200811-125007941
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Official Citation:Buchman, A., Shriner, I., Yang, T. et al. Engineered reproductively isolated species drive reversible population replacement. Nat Commun 12, 3281 (2021).
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:104911
Deposited By: Tony Diaz
Deposited On:11 Aug 2020 20:16
Last Modified:07 Jun 2021 23:11

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