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Medusa: A Novel Gene Drive System for Confined Suppression of Insect Populations

Marshall, John M. and Hay, Bruce A. (2014) Medusa: A Novel Gene Drive System for Confined Suppression of Insect Populations. PLoS ONE, 9 (7). e102694. ISSN 1932-6203. PMCID PMC4108329. doi:10.1371/journal.pone.0102694.

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Gene drive systems provide novel opportunities for insect population suppression by driving genes that confer a fitness cost into pest or disease vector populations; however regulatory issues arise when genes are capable of spreading across international borders. Gene drive systems displaying threshold properties provide a solution since they can be confined to local populations and eliminated through dilution with wild-types. We propose a novel, threshold-dependent gene drive system, Medusa, capable of inducing a local and reversible population crash. Medusa consists of four components - two on the X chromosome, and two on the Y chromosome. A maternally-expressed, X-linked toxin and a zygotically-expressed, Y-linked antidote results in suppression of the female population and selection for the presence of the transgene-bearing Y because only male offspring of Medusa-bearing females are protected from the effects of the toxin. At the same time, the combination of a zygotically-expressed, Y-linked toxin and a zygotically-expressed, X-linked antidote selects for the transgene-bearing X in the presence of the transgene-bearing Y. Together these chromosomes create a balanced lethal system that spreads while selecting against females when present above a certain threshold frequency. Simple population dynamic models show that an all-male release of Medusa males, carried out over six generations, is expected to induce a population crash within 12 generations for modest release sizes on the order of the wild population size. Re-invasion of non-transgenic insects into a suppressed population can result in a population rebound; however this can be prevented through regular releases of modest numbers of Medusa males. Finally, we outline how Medusa could be engineered with currently available molecular tools.

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Additional Information:© 2014 Marshall, Hay. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Editor: João Pinto, Instituto de Higiene e Medicina Tropical, Portugal. Received December 22, 2012; Accepted June 23, 2014; Published July 23, 2014. Funding: John Marshall acknowledges support from a fellowship from the Medical Research Council/Department for International Development, UK and Bruce Hay was supported by grant DP1GM1053A from the National Institutes of Health, USA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments: The authors thank Omar Akbari for helpful insight into molecular issues and six anonymous reviewers whose valuable comments helped improve previous versions of the manuscript. Author Contributions: Conceived and designed the experiments: JMM BAH. Performed the experiments: JMM. Analyzed the data: JMM. Wrote the paper: JMM BAH.
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Medical Research Council/Department for International Development (UK)UNSPECIFIED
Issue or Number:7
PubMed Central ID:PMC4108329
Record Number:CaltechAUTHORS:20140829-114101487
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Official Citation:Marshall JM, Hay BA (2014) Medusa: A Novel Gene Drive System for Confined Suppression of Insect Populations. PLoS ONE 9(7): e102694. doi:10.1371/ journal.pone.0102694
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:49068
Deposited By: Ruth Sustaita
Deposited On:29 Aug 2014 20:02
Last Modified:10 Nov 2021 18:39

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