Dataset Information

Introducing transgenes into insect populations using combined gene-drive strategies: modeling and analysis.

ABSTRACT: Engineered underdominance (EU), meiotic drive (MD) and Wolbachia have been proposed as mechanisms for driving anti-pathogen transgenes into natural populations of insect vectors of human diseases. EU can drive transgenes to high and stable frequencies but requires the release of sizeable numbers of engineered insects. MD and Wolbachia either cannot maintain high frequencies of transgenes or lack appropriate expression in critical tissues, but both can drive the transgenes to spread from very low initial frequencies. Here we use mathematical models to assess the utility of combining EU with MD or with Wolbachia. Under some conditions, the combination of EU and MD results in a more efficient transgene-drive strategy than either mechanism alone. This combined strategy could drive the transgenes to stable fixation and would require fewer released insects than EU alone, especially when only males are released. However, a combination of EU and Wolbachia does not work better than EU alone because it requires the release of even more engineered insects.

SUBMITTER: Huang Y

PROVIDER: S-EPMC2099304 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature

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Introducing transgenes into insect populations using combined gene-drive strategies: modeling and analysis.

Huang Yunxin Y Magori Krisztian K Lloyd Alun L AL Gould Fred F

Insect biochemistry and molecular biology 20070613 10

Engineered underdominance (EU), meiotic drive (MD) and Wolbachia have been proposed as mechanisms for driving anti-pathogen transgenes into natural populations of insect vectors of human diseases. EU can drive transgenes to high and stable frequencies but requires the release of sizeable numbers of engineered insects. MD and Wolbachia either cannot maintain high frequencies of transgenes or lack appropriate expression in critical tissues, but both can drive the transgenes to spread from very low ...[more]

PMID: 17785193

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Project description:BackgroundThe 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 UDMEL-to explore their ability to be confined and remediated.ResultsWe 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. UDMEL 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.ConclusionsOur 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.

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

Introducing transgenes into insect populations using combined gene-drive strategies: modeling and analysis.

Publications

Introducing transgenes into insect populations using combined gene-drive strategies: modeling and analysis.

Similar Datasets

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