Efficient allelic-drive in Drosophila

Annabel Guichard, Tisha Haque, Marketta Bobik, Xiang-Ru S. Xu, Carissa Klanseck, Raja Babu Singh Kushwah, Mateus Berni, Bhagyashree Kaduskar, Valentino M. Gantz and Ethan Bier ()
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Annabel Guichard: University of California, San Diego
Tisha Haque: University of California, San Diego
Marketta Bobik: University of California, San Diego
Xiang-Ru S. Xu: University of California, San Diego
Carissa Klanseck: University of California, San Diego
Raja Babu Singh Kushwah: University of California, San Diego
Mateus Berni: Universidade Federal do Rio de Janeiro
Bhagyashree Kaduskar: University of California, San Diego
Valentino M. Gantz: University of California, San Diego
Ethan Bier: University of California, San Diego

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: Abstract Gene-drive systems developed in several organisms result in super-Mendelian inheritance of transgenic insertions. Here, we generalize this “active genetic” approach to preferentially transmit allelic variants (allelic-drive) resulting from only a single or a few nucleotide alterations. We test two configurations for allelic-drive: one, copy-cutting, in which a non-preferred allele is selectively targeted for Cas9/guide RNA (gRNA) cleavage, and a more general approach, copy-grafting, that permits selective inheritance of a desired allele located in close proximity to the gRNA cut site. We also characterize a phenomenon we refer to as lethal-mosaicism that dominantly eliminates NHEJ-induced mutations and favors inheritance of functional cleavage-resistant alleles. These two efficient allelic-drive methods, enhanced by lethal mosaicism and a trans-generational drive process we refer to as “shadow-drive”, have broad practical applications in improving health and agriculture and greatly extend the active genetics toolbox.

Date: 2019
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DOI: 10.1038/s41467-019-09694-w

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