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Split drive killer-rescue provides a novel threshold-dependent gene drive.

ABSTRACT: A wide range of gene drive mechanisms have been proposed that are predicted to increase in frequency within a population even when they are deleterious to individuals carrying them. This also allows associated desirable genetic material ("cargo genes") to increase in frequency. Gene drives have garnered much attention for their potential use against a range of globally important problems including vector borne disease, crop pests and invasive species. Here we propose a novel gene drive mechanism that could be engineered using a combination of toxin-antidote and CRISPR components, each of which are already being developed for other purposes. Population genetics mathematical models are developed here to demonstrate the threshold-dependent nature of the proposed system and its robustness to imperfect homing, incomplete penetrance of toxins and transgene fitness costs, each of which are of practical significance given that real-world components inevitably have such imperfections. We show that although end-joining repair mechanisms may cause the system to break down, under certain conditions, it should persist over time scales relevant for genetic control programs. The potential of such a system to provide localised population suppression via sex ratio distortion or female-specific lethality is also explored. Additionally, we investigate the effect on introduction thresholds of adding an extra CRISPR base element, showing that this may either increase or decrease dependent on parameter context.

SUBMITTER: Edgington MP

PROVIDER: S-EPMC7689494 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Split drive killer-rescue provides a novel threshold-dependent gene drive.

Edgington Matthew P MP Harvey-Samuel Tim T Alphey Luke L

Scientific reports 20201125 1

A wide range of gene drive mechanisms have been proposed that are predicted to increase in frequency within a population even when they are deleterious to individuals carrying them. This also allows associated desirable genetic material ("cargo genes") to increase in frequency. Gene drives have garnered much attention for their potential use against a range of globally important problems including vector borne disease, crop pests and invasive species. Here we propose a novel gene drive mechanism ...[more]

PMID: 33239631

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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.

Dataset Information

Split drive killer-rescue provides a novel threshold-dependent gene drive.

Publications

Split drive killer-rescue provides a novel threshold-dependent gene drive.

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