Exploiting a Y chromosome-linked Cas9 for sex selection and gene drive

Stephanie Gamez, Duverney Chaverra-Rodriguez, Anna Buchman, Nikolay P. Kandul, Stelia C. Mendez-Sanchez, Jared B. Bennett, Héctor M. Sánchez C., Ting Yang, Igor Antoshechkin, Jonny E. Duque, Philippos A. Papathanos, John M. Marshall and Omar S. Akbari ()
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Stephanie Gamez: University of California, San Diego
Duverney Chaverra-Rodriguez: University of California, San Diego
Anna Buchman: University of California, San Diego
Nikolay P. Kandul: University of California, San Diego
Stelia C. Mendez-Sanchez: University of California, San Diego
Jared B. Bennett: Biophysics Graduate Group, University of California
Héctor M. Sánchez C.: School of Public Health, University of California
Ting Yang: University of California, San Diego
Igor Antoshechkin: California Institute of Technology
Jonny E. Duque: University of California, San Diego
Philippos A. Papathanos: Food and Environment, Hebrew University of Jerusalem
John M. Marshall: School of Public Health, University of California
Omar S. Akbari: University of California, San Diego

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract CRISPR-based genetic engineering tools aimed to bias sex ratios, or drive effector genes into animal populations, often integrate the transgenes into autosomal chromosomes. However, in species with heterogametic sex chromsomes (e.g. XY, ZW), sex linkage of endonucleases could be beneficial to drive the expression in a sex-specific manner to produce genetic sexing systems, sex ratio distorters, or even sex-specific gene drives, for example. To explore this possibility, here we develop a transgenic line of Drosophila melanogaster expressing Cas9 from the Y chromosome. We functionally characterize the utility of this strain for both sex selection and gene drive finding it to be quite effective. To explore its utility for population control, we built mathematical models illustrating its dynamics as compared to other state-of-the-art systems designed for both population modification and suppression. Taken together, our results contribute to the development of current CRISPR genetic control tools and demonstrate the utility of using sex-linked Cas9 strains for genetic control of animals.

Date: 2021
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DOI: 10.1038/s41467-021-27333-1

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