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...

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Autores principales:	Matthew P. Edgington, Tim Harvey-Samuel, Luke Alphey
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/aa91292f3e004e3f8e3ce8c1e2d16d26
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spelling	oai:doaj.org-article:aa91292f3e004e3f8e3ce8c1e2d16d262021-12-02T15:09:40ZSplit drive killer-rescue provides a novel threshold-dependent gene drive10.1038/s41598-020-77544-72045-2322https://doaj.org/article/aa91292f3e004e3f8e3ce8c1e2d16d262020-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-77544-7https://doaj.org/toc/2045-2322Abstract 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.Matthew P. EdgingtonTim Harvey-SamuelLuke AlpheyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Matthew P. Edgington Tim Harvey-Samuel Luke Alphey Split drive killer-rescue provides a novel threshold-dependent gene drive
description	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.
format	article
author	Matthew P. Edgington Tim Harvey-Samuel Luke Alphey
author_facet	Matthew P. Edgington Tim Harvey-Samuel Luke Alphey
author_sort	Matthew P. Edgington
title	Split drive killer-rescue provides a novel threshold-dependent gene drive
title_short	Split drive killer-rescue provides a novel threshold-dependent gene drive
title_full	Split drive killer-rescue provides a novel threshold-dependent gene drive
title_fullStr	Split drive killer-rescue provides a novel threshold-dependent gene drive
title_full_unstemmed	Split drive killer-rescue provides a novel threshold-dependent gene drive
title_sort	split drive killer-rescue provides a novel threshold-dependent gene drive
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/aa91292f3e004e3f8e3ce8c1e2d16d26
work_keys_str_mv	AT matthewpedgington splitdrivekillerrescueprovidesanovelthresholddependentgenedrive AT timharveysamuel splitdrivekillerrescueprovidesanovelthresholddependentgenedrive AT lukealphey splitdrivekillerrescueprovidesanovelthresholddependentgenedrive
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Split drive killer-rescue provides a novel threshold-dependent gene drive

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