The spatial spread and the persistence of gene drives are affected by demographic feedbacks, density dependence and Allee effects

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 8, 2024

Abstract Homing gene drive alleles bias their own transmission by converting wild-type into alleles. If introduced in a natural population, they might fix within relatively small number of generations, even if are deleterious. No engineered homing organisms have been released the wild so far, and modelling is essential to develop clear understanding potential outcomes such releases. We use deterministic models investigate how different demographic features affect spatial spread drive. Building on previous work, we first consider effect intrinsic population growth rate spread. confirm that including dynamics can change compared model ignoring changes sizes, because density oppose Secondly, study consequences an Allee effect, find it makes more prone eradication following Finally, effects fitness component which dependence operates (fecundity or survival), affects speed invasion space, accentuate effect. These results importance checking robustness underlying assumptions, especially be used for risk assessment.

Language: Английский

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Quantifying Fitness Costs in Transgenic <em>Aedes aegypti</em> Mosquitoes

Journal of Visualized Experiments, Journal Year: 2023, Volume and Issue: 199

Published: Sept. 15, 2023

Transgenic mosquitoes often display fitness costs compared to their wild-type counterparts. In this regard, cost studies involve collecting life parameter data from genetically modified and comparing them lacking transgenes the same genetic background. This manuscript illustrates how measure common history traits in mosquito Aedes aegypti, including fecundity, wing size shape, fertility, sex ratio, viability, development times, male contribution, adult longevity. These parameters were chosen because they reflect reproductive success, are simple measure, commonly reported literature. The representative results quantify associated with either a gene knock-out or single insertion of drive element. Standardizing collected is important such may be used compare health transgenic generated across model transgene fixation rate simulated population. Although protocol specific for also other species experimental treatment conditions, caveat that certain biological contexts require special adaptations.

Language: Английский

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Population suppression with dominant female-lethal alleles is boosted by homing gene drive

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 5, 2023

Abstract Methods to suppress pest insect populations using genetic constructs and repeated releases of male homozygotes have recently been shown be an attractive alternative older sterile technique based on radiation. Female-specific lethal alleles substantially increased power, but still require large, sustained transgenic releases. Gene drive bias their own inheritance spread throughout populations, potentially allowing population suppression with a single, small-size release. However, drives often suffer from efficiency issues, the most well-studied type, homing drives, tend without limit. In this study, we show that coupling female-specific gene allowed substantial improvement in while retaining self-limiting nature (and thus confinement) allele strategy. Using mosquito model, required sizes for elimination variety scenarios, including different density growth curves, comparisons other systems. Resistance reduced power method, these could overcome by targeting essential also providing rescue. A proof-of-principle demonstration system Drosophila melanogaster was effective both basing its achieving high lethality among females inherit construct absence antibiotic. Overall, our study shows improvements can achieved systems combining them drive.

Language: Английский

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A population modification gene drive targeting bothSaglinandLipophorinimpairsPlasmodiumtransmission inAnophelesmosquitoes

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: July 8, 2022

Abstract Lipophorin is an essential, highly expressed lipid transport protein that secreted and circulates in insect hemolymph. We hijacked the Anopheles coluzzii gene to make it co-express a single-chain version of antibody 2A10, which binds sporozoites malaria parasite Plasmodium falciparum . The resulting transgenic mosquitoes show markedly decreased ability transmit berghei expressing P. circumsporozoite protein. To force spread this anti-malarial transgene mosquito population, we designed tested several CRISPR/Cas9-based drives. One these installed in, disrupts, pro-parasitic Saglin also cleaves wild-type Lipophorin, causing modified replace wild type hitch-hike together with drive. Although generating drive-resistant alleles showing instability its gRNA-encoding multiplex array, -based drive reached high levels caged populations efficiently promoted simultaneous antimalarial Lipophorin::Sc2A10 allele. This combination expected decrease transmission via two different mechanisms. work contributes design novel strategies transgenes mosquitoes, illustrates some unexpected outcomes encountered when establishing population modification

Language: Английский

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Genetic and geographic population structure in the malaria vector, Anopheles farauti, provides a candidate model system for pioneering confinable gene-drive releases

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 7, 2023

Indoor insecticide applications are the primary tool for reducing malaria transmission in Solomon Archipelago, a region where Anopheles farauti is only common vector. Due to evolution of behavioural resistance some An. populations, these have become less effective. New control interventions therefore needed this region, and gene-drives provide promising new technology. In considering developing population-specific (local) gene-drive farauti, we detail species’ population genetic structure using microsatellites whole mitogenomes, finding many spatially confined populations both within between landmasses. This strong suggests that would be useful system population-specific, confinable field release, private alleles can used as Cas9 targets. Previous work on gambiae has Cardinal gene development global replacement gene-drive. We also analyse assess whether it may suitable target engineer modification local populations. Despite extensive observed microsatellites, one remote island from Vanuatu contained fixed at locus. Nonetheless, study provides an initial framework further genomic investigations discover high-frequency allele targets localized enable strains modifying localised with minimal chance escape low-risk route trial evaluations.

Language: Английский

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