title: A synthetic gene drive system for local, reversible modification and suppression of insect populations.
abstract: Replacement of wild insect populations with genetically modified individuals unable to transmit disease provides a self-perpetuating method of disease prevention but requires a gene drive mechanism to spread these traits to high frequency. Drive mechanisms requiring that transgenes exceed a threshold frequency in order to spread are attractive because they bring about local but not global replacement, and transgenes can be eliminated through dilution of the population with wild-type individuals. These features are likely to be important in many social and regulatory contexts. Here we describe the first creation of a synthetic threshold-dependent gene drive system, designated maternal-effect lethal underdominance (UD(MEL)), in which two maternally expressed toxins, located on separate chromosomes, are each linked with a zygotic antidote able to rescue maternal-effect lethality of the other toxin. We demonstrate threshold-dependent replacement in single- and two-locus configurations in Drosophila. Models suggest that transgene spread can often be limited to local environments. They also show that in a population in which single-locus UD(MEL) has been carried out, repeated release of wild-type males can result in population suppression, a novel method of genetic population manipulation.
authors.affiliation: Division of Biology, MC 156-29, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Omar S
authors.initials: OS
authors.lastname: Akbari
authors.forename: Kelly D
authors.initials: KD
authors.lastname: Matzen
authors.forename: John M
authors.initials: JM
authors.lastname: Marshall
authors.forename: Haixia
authors.initials: H
authors.lastname: Huang
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Ward
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Hay
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000502:physiology; D000931:Antidotes / Q000378:metabolism; D002875:Chromosomes; D004331:Drosophila melanogaster / Q000235:genetics* / Q000502:physiology; D005260:Female; D017344:Genes, Insect; D005813:Genes, Synthetic; D056084:Genetic Fitness; D008040:Genetic Linkage; D008297:Male; D008957:Models, Genetic; D011157:Population Dynamics; D014118:Toxins, Biological / Q000235:genetics / Q000378:metabolism; D019076:Transgenes
chemical_list: D000931:Antidotes; D014118:Toxins, Biological
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