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Engineered Reciprocal Chromosome Translocations Drive High Threshold, Reversible Population Replacement in Drosophila

Buchman, Anna B. and Ivy, Tobin and Marshall, John M. and Akbari, Omar S. and Hay, Bruce A. (2018) Engineered Reciprocal Chromosome Translocations Drive High Threshold, Reversible Population Replacement in Drosophila. ACS Synthetic Biology, 7 (5). pp. 1359-1370. ISSN 2161-5063. doi:10.1021/acssynbio.7b00451.

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Replacement of wild insect populations with transgene-bearing individuals unable to transmit disease or survive under specific environmental conditions using gene drive provides a self-perpetuating method of disease prevention. Mechanisms that require the gene drive element and linked cargo to exceed a high threshold frequency in order for spread to occur are attractive because they offer several points of control: they bring about local, but not global population replacement; and transgenes can be eliminated by reintroducing wildtypes into the population so as to drive the frequency of transgenes below the threshold frequency required for drive. Reciprocal chromosome translocations were proposed as a tool for bringing about high threshold population replacement in 1940 and 1968. However, translocations able to achieve this goal have only been reported once, in the spider mite Tetranychus urticae, a haplo-diploid species in which there is strong selection in haploid males for fit homozygotes. We report the creation of engineered translocation-bearing strains of Drosophila melanogaster, generated through targeted chromosomal breakage and homologous recombination. These strains drive high threshold population replacement in laboratory populations. While it remains to be shown that engineered translocations can bring about population replacement in wild populations, these observations suggest that further exploration of engineered translocations as a tool for controlled population replacement is warranted.

Item Type:Article
Related URLs:
URLURL TypeDescription Information Paper
Buchman, Anna B.0000-0002-8775-6147
Akbari, Omar S.0000-0002-6853-9884
Additional Information:© 2018 American Chemical Society. Received: December 12, 2017; Published: April 2, 2018. Work in the laboratory of B.A.H. (B.A.H., O.S.A., A.B.B., and T.I.) was supported by the U.S. Army Research Laboratory and the U.S. Army Research Office under Contract W911NF-11-2-0055 to the California Institute of Technology, and the USDA and CRDF. Work at UCSD (O.S.A. and A.B.) was supported by an NIH-K22 Career Transition award (5K22AI113060), an NIH Exploratory/Developmental Research Grant Award (1R21AI123937), and a Defense Advanced Research Project Agency (DARPA) Safe Genes Program Grant (HR0011-17-2-0047) awarded to O.S.A. J.M.M. was supported by funding from The Parker Foundation through a gift to the University of California, San Francisco, Global Health Group Malaria Elimination Initiative. T.I. was supported by a National Institute of General Medical Sciences grant 2T32GM007616. Author Contributions: A.B., O.S.A, and B.A.H. conceived and designed experiments. T.I., J.M.M., A.B., and O.S.A. performed all mathematical, molecular, and genetic experiments. All authors analyzed the data, contributed to the writing, and approved the final manuscript. The authors declare the following competing financial interest(s): A.B, O.S.A and B.A.H have a patent pending related to population control using engineered translocations.
Funding AgencyGrant Number
Army Research LaboratoryUNSPECIFIED
Army Research Office (ARO)W911NF-11-2-0055
United States Department of Agriculture (USDA)UNSPECIFIED
Defense Advanced Research Project Agency (DARPA)HR0011-17-2-0047
Parker FoundationUNSPECIFIED
NIH Predoctoral Fellowship2T32GM007616
Subject Keywords:gene drive, selfish genetic element, vector control, mosquito, malaria, dengue, UDMEL, engineered translocations, self-propagating, unbreakable, public acceptance
Issue or Number:5
Record Number:CaltechAUTHORS:20180423-100713570
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Official Citation:Engineered Reciprocal Chromosome Translocations Drive High Threshold, Reversible Population Replacement in Drosophila. Anna B. Buchman, Tobin Ivy, John M. Marshall, Omar S. Akbari, and Bruce A. Hay. ACS Synthetic Biology 2018 7 (5), 1359-1370. DOI: 10.1021/acssynbio.7b00451
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:86005
Deposited By: Tony Diaz
Deposited On:25 Apr 2018 18:17
Last Modified:15 Nov 2021 20:34

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