Anopheles homing suppression drive candidates exhibit unexpected performance differences in simulations with spatial structure
Abstract
Recent experiments have produced several Anopheles gambiae homing gene drives that disrupt female fertility genes, thereby eventually inducing population collapse. Such drives may be highly effective tools to combat malaria. One such homing drive, based on the zpg promoter driving CRISPR/Cas9, was able to eliminate a cage population of mosquitoes. A second version, purportedly improved upon the first by incorporating an X-shredder element (which biases inheritance towards male offspring), was similarly successful. Here, we analyze experimental data from each of these gene drives to extract their characteristics and performance parameters and compare these to previous interpretations of their experimental performance. We assess each suppression drive within an individual-based simulation framework that models mosquito population dynamics in continuous space. We find that the combined homing/X-shredder drive is actually less effective at population suppression within the context of our mosquito population model. In particular, the combined drive often fails to completely suppress the population, instead resulting in an unstable equilibrium between drive and wild-type alleles. By contrast, otherwise similar drives based on the nos promoter may prove to be more promising candidates for future development than originally thought.
Data availability
All SLiM files for the implementation of these suppression drives are available on GitHub (https://github.com/jchamper/ChamperLab/tree/main/Mosquito-Drive-Modeling).
Article and author information
Author details
Funding
NIH (F32AI138476)
- Jackson Champer
NIH (R01GM127418)
- Philipp W Messer
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- George H Perry, Pennsylvania State University, United States
Version history
- Preprint posted: March 28, 2022 (view preprint)
- Received: March 31, 2022
- Accepted: October 14, 2022
- Accepted Manuscript published: October 14, 2022 (version 1)
- Version of Record published: October 25, 2022 (version 2)
Copyright
© 2022, Champer et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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