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Inherently confinable split-drive systems in Drosophila

Author

Listed:
  • Gerard Terradas

    (University of California, San Diego
    University of California, San Diego)

  • Anna B. Buchman

    (University of California, San Diego)

  • Jared B. Bennett

    (University of California)

  • Isaiah Shriner

    (University of California, San Diego)

  • John M. Marshall

    (University of California
    Innovative Genomics Institute)

  • Omar S. Akbari

    (University of California, San Diego)

  • Ethan Bier

    (University of California, San Diego
    University of California, San Diego)

Abstract

CRISPR-based gene-drive systems, which copy themselves via gene conversion mediated by the homology-directed repair (HDR) pathway, have the potential to revolutionize vector control. However, mutant alleles generated by the competing non-homologous end-joining (NHEJ) pathway, resistant to Cas9 cleavage, can interrupt the spread of gene-drive elements. We hypothesized that drives targeting genes essential for viability or reproduction also carrying recoded sequences that restore endogenous gene functionality should benefit from dominantly-acting maternal clearance of NHEJ alleles combined with recessive Mendelian culling processes. Here, we test split gene-drive (sGD) systems in Drosophila melanogaster that are inserted into essential genes required for viability (rab5, rab11, prosalpha2) or fertility (spo11). In single generation crosses, sGDs copy with variable efficiencies and display sex-biased transmission. In multigenerational cage trials, sGDs follow distinct drive trajectories reflecting their differential tendencies to induce target chromosome damage and/or lethal/sterile mosaic Cas9-dependent phenotypes, leading to inherently confinable drive outcomes.

Suggested Citation

  • Gerard Terradas & Anna B. Buchman & Jared B. Bennett & Isaiah Shriner & John M. Marshall & Omar S. Akbari & Ethan Bier, 2021. "Inherently confinable split-drive systems in Drosophila," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21771-7
    DOI: 10.1038/s41467-021-21771-7
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    Cited by:

    1. Frieß, Johannes L. & Lalyer, Carina R. & Giese, Bernd & Simon, Samson & Otto, Mathias, 2023. "Review of gene drive modelling and implications for risk assessment of gene drive organisms," Ecological Modelling, Elsevier, vol. 478(C).

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