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Published May 2011 | Published
Journal Article Open

Inverse Medea as a Novel Gene Drive System for Local Population Replacement: A Theoretical Analysis

Abstract

One strategy to control mosquito-borne diseases, such as malaria and dengue fever, on a regional scale is to use gene drive systems to spread disease-refractory genes into wild mosquito populations. The development of a synthetic Medea element that has been shown to drive population replacement in laboratory Drosophila populations has provided encouragement for this strategy but has also been greeted with caution over the concern that transgenes may spread into countries without their consent. Here, we propose a novel gene drive system, inverse Medea, which is strong enough to bring about local population replacement but is unable to establish itself beyond an isolated release site. The system consists of 2 genetic components—a zygotic toxin and maternal antidote—which render heterozygous offspring of wild-type mothers unviable. Through population genetic analysis, we show that inverse Medea will only spread when it represents a majority of the alleles in a population. The element is best located on an autosome and will spread to fixation provided any associated fitness costs are dominant and to very high frequency otherwise. We suggest molecular tools that could be used to build the inverse Medea system and discuss its utility for a confined release of transgenic mosquitoes.

Additional Information

© 2011 The American Genetic Association. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses?by-nc/2.0/uk/) which permits unrestricted non-commercial use distribution, and reproduction in any medium, provided the original work is properly cited. Received November 14, 2010; Revised February 10, 2011; Accepted March 1, 2011. Corresponding Editor: Dr Howard Ross. Funding: National Institutes of Health (DP1 OD003878 to B.A.H.). The authors would like to thank Geoffrey Pittman for helpful discussions on how to build the inverse Medea system, and 2 anonymous reviewers whose constructive comments have improved the manuscript.

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