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. 2018 May 1;115(18):4725-4730.
doi: 10.1073/pnas.1713139115. Epub 2018 Apr 17.

Synthetically Engineered Medea Gene Drive System in the Worldwide Crop Pest Drosophila suzukii

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Free PMC article

Synthetically Engineered Medea Gene Drive System in the Worldwide Crop Pest Drosophila suzukii

Anna Buchman et al. Proc Natl Acad Sci U S A. .
Free PMC article

Abstract

Synthetic gene drive systems possess enormous potential to replace, alter, or suppress wild populations of significant disease vectors and crop pests; however, their utility in diverse populations remains to be demonstrated. Here, we report the creation of a synthetic Medea gene drive system in a major worldwide crop pest, Drosophila suzukii We demonstrate that this drive system, based on an engineered maternal "toxin" coupled with a linked embryonic "antidote," is capable of biasing Mendelian inheritance rates with up to 100% efficiency. However, we find that drive resistance, resulting from naturally occurring genetic variation and associated fitness costs, can be selected for and hinder the spread of such a drive. Despite this, our results suggest that this gene drive could maintain itself at high frequencies in a wild population and spread to fixation if either its fitness costs or toxin resistance were reduced, providing a clear path forward for developing future such systems in this pest.

Keywords: Drosophila suzukii; Medea; gene drive.

Conflict of interest statement

Conflict of interest statement: A.B. and O.S.A. have filed a patent on the Suzukii Medea drive system.

Figures

Fig. 1.
Fig. 1.
A synthetic Medea system in D. suzukii. A D. suzukii Medea transgene was generated to comprise an miRNA “toxin” targeting the 5′UTR of D. suzukii myd88 expressed under the predicted D. suzukii female germline–specific BicC promoter, an “antidote” consisting of D. suzukii myd88 coding region driven by the predicted D. suzukii early embryo-specific bnk promoter, and two separate transformation markers, eGFP under control of the eye-specific 3xP3 promoter and dsRed under control of the ubiquitous hr5-IE1 promoter (A). During normal development maternal myd88 is deposited into the embryo, where it is required for normal development (B). The Medea miRNA toxin targets myd88 mRNA during oogenesis, preventing proper deposition into the embryo and causing embryonic lethality in progeny that lack the Medea system (C). In embryos that possess a copy of the Medea system, a version of myd88 that is insensitive to the miRNA toxin is expressed during early embryogenesis, rescuing miRNA-induced lethality (D). When heterozygous Medea males are crossed out to WT females, all progeny survive since the maternal toxin is not expressed; however, when heterozygous Medea females are crossed to WT males, 50% of the progeny, the ones that fail to inherit Medea, perish. When heterozygous females are crossed to heterozygous males, 75% of the progeny inherit Medea, either from the mother or the father, and survive, while those that fail to inherit a Medea system perish (E). The hr5-IE1 promotes robust expression of dsRed in both D. suzukii adults and larvae, allowing for facile identification of Medea-bearing individuals (F).
Fig. 2.
Fig. 2.
Medea functions in diverse populations of D. suzukii. Heterozygous Medea/+ individuals were crossed with eight geographically distinct D. suzukii populations and Medea inheritance was measured. Overall, Medea biased inheritance with rates ranging from 87.6 to 100%, suggesting that a Medea system generated in the laboratory could be utilized to manipulate some, but not all, diverse wild populations of D. suzukii. Green stars indicate the collection locations of the flies tested, green pie charts indicate the percentage Medea inheritance observed from heterozygous Medea/+ females, and shaded areas on the map indicate locations where D. suzukii populations have been confirmed. The Corvallis, OR strain was our reference D. suzukii strain used to engineer the Medea.
Fig. 3.
Fig. 3.
Observed and predicted dynamics of the D. suzukii Medea drive system. Population cage experiments were set up by mating WT (+/+) and heterozygous Medea (Medea/+) or homozygous Medea males (Medea/Medea) with WT (+/+) females, producing a frequency of heterozygotes (Medea/+) in the first generation of 25–100%. Population counts were monitored over 19 generations. Results from these experiments are shown as solid lines, with fitted model predictions shown as dashed lines. Observed data are consistent with a toxin efficiency of 100% in Medea-susceptible mothers, 93% in Medea-resistant mothers (95% CrI: 90–95%), a heterozygote fitness cost of 28% (95% CrI: 27–30%), a homozygote fitness cost of 65% (95% CrI: 62–67%), and an initial resistant allele population frequency of 78% (95% CrI: 57–97%). For high initial heterozygote frequencies (90–100%), the drive is capable of manipulating inheritance in its favor to maintain its presence at high population frequencies, despite a fitness cost. For lower initial heterozygote frequencies (∼50% or less), the drive is eliminated from the population.

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