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Proc Natl Acad Sci U S A. 2018 Jun 12;115(24):6189-6194. doi: 10.1073/pnas.1713825115. Epub 2018 May 29.

Consequences of resistance evolution in a Cas9-based sex conversion-suppression gene drive for insect pest management.

Author information

1
Department of Developmental Biology, Johann Friedrich Blumenbach Institute of Zoology and Anthropology, Göttingen Center of Molecular Biosciences, University of Göttingen, 37077 Göttingen, Germany.
2
Göttingen Graduate Center for Neurosciences, Biophysics, and Molecular Biosciences, University of Göttingen, 37077 Göttingen, Germany.
3
Molecular Cell Dynamics, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
4
Divisions of Epidemiology and Biostatistics, School of Public Health, University of California, Berkeley, CA 94720.
5
Department of Developmental Biology, Johann Friedrich Blumenbach Institute of Zoology and Anthropology, Göttingen Center of Molecular Biosciences, University of Göttingen, 37077 Göttingen, Germany; ewimmer@gwdg.de.

Abstract

The use of a site-specific homing-based gene drive for insect pest control has long been discussed, but the easy design of such systems has become possible only with the recent establishment of CRISPR/Cas9 technology. In this respect, novel targets for insect pest management are provided by new discoveries regarding sex determination. Here, we present a model for a suppression gene drive designed to cause an all-male population collapse in an agricultural pest insect. To evaluate the molecular details of such a sex conversion-based suppression gene drive experimentally, we implemented this strategy in Drosophila melanogaster to serve as a safe model organism. We generated a Cas9-based homing gene-drive element targeting the transformer gene and showed its high efficiency for sex conversion from females to males. However, nonhomologous end joining increased the rate of mutagenesis at the target site, which resulted in the emergence of drive-resistant alleles and therefore curbed the gene drive. This confirms previous studies that simple homing CRISPR/Cas9 gene-drive designs will be ineffective. Nevertheless, by performing population dynamics simulations using the parameters we obtained in D. melanogaster and by adjusting the model for the agricultural pest Ceratitis capitata, we were able to identify adequate modifications that could be successfully applied for the management of wild Mediterranean fruit fly populations using our proposed sex conversion-based suppression gene-drive strategy.

KEYWORDS:

Tephritid fruit flies; homing endonuclease; integrated pest management; molecular entomology; sex reversal

PMID:
29844184
PMCID:
PMC6004448
DOI:
10.1073/pnas.1713825115
[Indexed for MEDLINE]
Free PMC Article

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