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Confinement of gene drive systems to local populations: A comparative analysis

Marshall, John M. and Hay, Bruce A. (2012) Confinement of gene drive systems to local populations: A comparative analysis. Journal of Theoretical Biology, 294 . pp. 153-171. ISSN 0022-5193. PMCID PMC3260013. doi:10.1016/j.jtbi.2011.10.032.

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Mosquito-borne diseases such as malaria and dengue fever pose a major health problem through much of the world. One approach to disease prevention involves the use of selfish genetic elements to drive disease-refractory genes into wild mosquito populations. Recently engineered synthetic drive systems have provided encouragement for this strategy; but at the same time have been greeted with caution over the concern that transgenes may spread into countries and communities without their consent. Consequently, there is also interest in gene drive systems that, while strong enough to bring about local population replacement, are unable to establish themselves beyond a partially isolated release site, at least during the testing phase. Here, we develop simple deterministic and stochastic models to compare the confinement properties of a variety of gene drive systems. Our results highlight several systems with desirable features for confinement—a high migration rate required to become established in neighboring populations, and low-frequency persistence in neighboring populations for moderate migration rates. Single-allele underdominance and single-locus engineered underdominance have the strongest confinement properties, but are difficult to engineer and require a high introduction frequency, respectively. Toxin–antidote systems such as Semele, Merea and two-locus engineered underdominance show promising confinement properties and require lower introduction frequencies. Killer-rescue is self-limiting in time, but is able to disperse to significant levels in neighboring populations. We discuss the significance of these results in the context of a phased release of transgenic mosquitoes, and the need for characterization of local ecology prior to a release.

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Additional Information:© 2011 Elsevier Ltd. Received 15 February 2011; Received in revised form 25 October 2011; Accepted 27 October 2011; Available online 9 November 2011. The authors would like to thank Catherine Ward for advice on modeling, Charles Taylor for helpful discussions on mosquito dispersal, and the editor and two anonymous reviewers whose constructive comments have greatly improved the manuscript. John M. Marshall was supported by grant number DP1 OD003878 to Bruce A. Hay from the National Institutes of Health, and by a grant from the Medical Research Council, UK.
Funding AgencyGrant Number
NIHDP1 OD003878
Medical Research Council (UK)UNSPECIFIED
Subject Keywords:Migration; Population replacement; Stochastic process; Transgenic mosquitoes; Underdominance
PubMed Central ID:PMC3260013
Record Number:CaltechAUTHORS:20120217-144654329
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Official Citation:John M. Marshall, Bruce A. Hay, Confinement of gene drive systems to local populations: A comparative analysis, Journal of Theoretical Biology, Volume 294, 7 February 2012, Pages 153-171, ISSN 0022-5193, 10.1016/j.jtbi.2011.10.032.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:29371
Deposited By: Tony Diaz
Deposited On:22 Feb 2012 00:47
Last Modified:09 Nov 2021 17:06

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