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Nat Commun. 2019 Apr 9;10(1):1640. doi: 10.1038/s41467-019-09694-w.

Efficient allelic-drive in Drosophila.

Author information

1
Section of Cell and Developmental Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0335, USA.
2
Tata Institute for Genetics and Society-India (TIGS), TIGS Center at inStem, Bangalore, 560065, India.
3
Instituto de Ciências Biomédicas (ICB), Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho 373, Ilha do Fundão, Rio de Janeiro, 21941-902, RJ, Brazil.
4
Post-graduate Program in Morphological Sciences, Federal University of Rio de Janeiro (PCM/UFRJ), Rio de Janeiro, 21941-902, RJ, Brazil.
5
Section of Cell and Developmental Biology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0335, USA. ebier@ucsd.edu.
6
Tata Institute for Genetics and Society-UCSD, La Jolla, CA, 92093-0335, USA. ebier@ucsd.edu.

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.

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