Dataset Information

Modeling confinement and reversibility of threshold-dependent gene drive systems in spatially-explicit Aedes aegypti populations.

ABSTRACT:

Background

The discovery of CRISPR-based gene editing and its application to homing-based gene drive systems has been greeted with excitement, for its potential to control mosquito-borne diseases on a wide scale, and concern, for the invasiveness and potential irreversibility of a release. Gene drive systems that display threshold-dependent behavior could potentially be used during the trial phase of this technology, or when localized control is otherwise desired, as simple models predict them to spread into partially isolated populations in a confineable manner, and to be reversible through releases of wild-type organisms. Here, we model hypothetical releases of two recently engineered threshold-dependent gene drive systems-reciprocal chromosomal translocations and a form of toxin-antidote-based underdominance known as UD^MEL-to explore their ability to be confined and remediated.

Results

We simulate releases of Aedes aegypti, the mosquito vector of dengue, Zika, and other arboviruses, in Yorkeys Knob, a suburb of Cairns, Australia, where previous biological control interventions have been undertaken on this species. We monitor spread to the neighboring suburb of Trinity Park to assess confinement. Results suggest that translocations could be introduced on a suburban scale, and remediated through releases of non-disease-transmitting male mosquitoes with release sizes on the scale of what has been previously implemented. UD^MEL requires fewer releases to introduce, but more releases to remediate, including of females capable of disease transmission. Both systems are expected to be confineable to the release site; however, spillover of translocations into neighboring populations is less likely.

Conclusions

Our analysis supports the use of translocations as a threshold-dependent drive system capable of spreading disease-refractory genes into Ae. aegypti populations in a confineable and reversible manner. It also highlights increased release requirements when incorporating life history and population structure into models. As the technology nears implementation, further ecological work will be essential to enhance model predictions in preparation for field trials.

SUBMITTER: Sanchez C HM

PROVIDER: S-EPMC7218562 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

Modeling confinement and reversibility of threshold-dependent gene drive systems in spatially-explicit Aedes aegypti populations.

Sánchez C Héctor M HM Bennett Jared B JB Wu Sean L SL Rašić Gordana G Akbari Omar S OS Marshall John M JM

BMC biology 20200512 1

<h4>Background</h4>The discovery of CRISPR-based gene editing and its application to homing-based gene drive systems has been greeted with excitement, for its potential to control mosquito-borne diseases on a wide scale, and concern, for the invasiveness and potential irreversibility of a release. Gene drive systems that display threshold-dependent behavior could potentially be used during the trial phase of this technology, or when localized control is otherwise desired, as simple models predic ...[more]

PMID: 32398005

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Project description:Dengue fever, the most prevalent global arboviral disease, represents an important public health problem in Indonesia. Control of dengue relies on the control of its main vector, the mosquito Aedes aegypti, yet nothing is known about the population history and genetic structure of this insect in Indonesia. Our aim was to assess the spatio-temporal population genetic structure of Ae. aegypti in Yogyakarta, a densely populated region on Java with common dengue outbreaks.We used multiple marker systems (microsatellites, nuclear and mitochondrial genome-wide single nucleotide polymorphisms generated via Restriction-site Associated DNA sequencing) to analyze 979 Ae. aegypti individuals collected from the Yogyakarta city and the surrounding hamlets during the wet season in 2011 and the following dry season in 2012. We employed individual- and group-based approaches for inferring genetic structure.We found that Ae. aegypti in Yogyakarta has spatially structured and seasonally stable populations. The spatial structuring was significant for the nuclear and mitochondrial markers, while the temporal structuring was non-significant. Nuclear markers identified three main genetic clusters, showing that hamlets have greater genetic isolation from each other and from the inner city sites. However, one hamlet experienced unrestricted mosquito interbreeding with the inner city, forming a single genetic cluster. Genetic distance was poorly correlated with the spatial distance among mosquito samples, suggesting stronger influence of human-assisted gene flow than active mosquito movement on spatial genetic structure. A star-shaped mitochondrial haplotype network and a significant R(2) test statistic (R(2)?=?0.0187, P?=?0.001) support the hypothesis that Ae. aegypti in Yogyakarta originated from a small or homogeneous source and has undergone a relatively recent demographic expansion.We report the first insights into the spatio-temporal genetic structure and the underlying processes in the dengue fever mosquito from Yogyakarta, Indonesia. Our results provide valuable information on the effectiveness of local control measures as well as guidelines for the implementation of novel biocontrol strategies such as release of Wolbachia-infected mosquitoes.

Project description:BackgroundDengue is the most important mosquito-borne viral disease affecting humans. The only prevention measure currently available is the control of its vectors, primarily Aedes aegypti. Recent advances in genetic engineering have opened the possibility for a new range of control strategies based on genetically modified mosquitoes. Assessing the potential efficacy of genetic (and conventional) strategies requires the availability of modeling tools that accurately describe the dynamics and genetics of Ae. aegypti populations.Methodology/principal findingsWe describe in this paper a new modeling tool of Ae. aegypti population dynamics and genetics named Skeeter Buster. This model operates at the scale of individual water-filled containers for immature stages and individual properties (houses) for adults. The biology of cohorts of mosquitoes is modeled based on the algorithms used in the non-spatial Container Inhabiting Mosquitoes Simulation Model (CIMSiM). Additional features incorporated into Skeeter Buster include stochasticity, spatial structure and detailed population genetics. We observe that the stochastic modeling of individual containers in Skeeter Buster is associated with a strongly reduced temporal variation in stage-specific population densities. We show that heterogeneity in container composition of individual properties has a major impact on spatial heterogeneity in population density between properties. We detail how adult dispersal reduces this spatial heterogeneity. Finally, we present the predicted genetic structure of the population by calculating F(ST) values and isolation by distance patterns, and examine the effects of adult dispersal and container movement between properties.Conclusions/significanceWe demonstrate that the incorporated stochasticity and level of spatial detail have major impacts on the simulated population dynamics, which could potentially impact predictions in terms of control measures. The capacity to describe population genetics confers the ability to model the outcome of genetic control methods. Skeeter Buster is therefore an important tool to model Ae. aegypti populations and the outcome of vector control measures.

Project description:Recently there have been significant advances in research on genetic strategies to control populations of disease-vectoring insects. Some of these strategies use the gene drive properties of selfish genetic elements to spread physically linked anti-pathogen genes into local vector populations. Because of the potential of these selfish elements to spread through populations, control approaches based on these strategies must be carefully evaluated to ensure a balance between the desirable spread of the refractoriness-conferring genetic cargo and the avoidance of potentially unwanted outcomes such as spread to non-target populations. There is also a need to develop better estimates of the economics of such releases. We present here an evaluation of two such strategies using a biologically realistic mathematical model that simulates the resident Aedes aegypti mosquito population of Iquitos, Peru. One strategy uses the selfish element Medea, a non-limited element that could permanently spread over a large geographic area; the other strategy relies on Killer-Rescue genetic constructs, and has been predicted to have limited spatial and temporal spread. We simulate various operational approaches for deploying these genetic strategies, and quantify the optimal number of released transgenic mosquitoes needed to achieve definitive spread of Medea-linked genes and/or high frequencies of Killer-Rescue-associated elements. We show that for both strategies the most efficient approach for achieving spread of anti-pathogen genes within three years is generally to release adults of both sexes in multiple releases over time. Even though females in these releases should not transmit disease, there could be public concern over such releases, making the less efficient male-only release more practical. This study provides guidelines for operational approaches to population replacement genetic strategies, as well as illustrates the use of detailed spatial models to assist in safe and efficient implementation of such novel genetic strategies.

Dataset Information

Modeling confinement and reversibility of threshold-dependent gene drive systems in spatially-explicit Aedes aegypti populations.

Background

Results

Conclusions

Publications

Modeling confinement and reversibility of threshold-dependent gene drive systems in spatially-explicit Aedes aegypti populations.

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