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A Killer–Rescue system for self-limiting gene drive of anti-pathogen constructs

A number of genetic mechanisms have been suggested for driving anti-pathogen genes into natural populations. Each of these mechanisms requires complex genetic engineering, and most are theoretically expected to permanently spread throughout the target species' geographical range. In the near te...

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Detalles Bibliográficos
Autores principales: Gould, Fred, Huang, Yunxin, Legros, Mathieu, Lloyd, Alun L
Formato: Texto
Lenguaje:English
Publicado: The Royal Society 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2572679/
https://www.ncbi.nlm.nih.gov/pubmed/18765342
http://dx.doi.org/10.1098/rspb.2008.0846
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author Gould, Fred
Huang, Yunxin
Legros, Mathieu
Lloyd, Alun L
author_facet Gould, Fred
Huang, Yunxin
Legros, Mathieu
Lloyd, Alun L
author_sort Gould, Fred
collection PubMed
description A number of genetic mechanisms have been suggested for driving anti-pathogen genes into natural populations. Each of these mechanisms requires complex genetic engineering, and most are theoretically expected to permanently spread throughout the target species' geographical range. In the near term, risk issues and technical limits of molecular methods could delay the development and use of these mechanisms. We propose a gene-drive mechanism that can be self-limiting over time and space, and is simpler to build. This mechanism involves one gene that codes for toxicity (killer) and a second that confers immunity to the toxic effects (rescue). We use population-genetic models to explore cases with one or two independent insertions of the killer gene and one insertion of the rescue gene. We vary the dominance and penetrance of gene action, as well as the magnitude of fitness costs. Even with the fitness costs of 10 per cent for each gene, the proportion of mosquitoes expected to transmit the pathogen decreases below 5 per cent for over 40 generations after one 2 : 1 release (engineered : wild) or after four 1 : 2 releases. Both the killer and rescue genes will be lost from the population over time, if the rescue construct has any associated fitness cost. Molecular approaches for constructing strains are discussed.
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spelling pubmed-25726792008-12-29 A Killer–Rescue system for self-limiting gene drive of anti-pathogen constructs Gould, Fred Huang, Yunxin Legros, Mathieu Lloyd, Alun L Proc Biol Sci Research Article A number of genetic mechanisms have been suggested for driving anti-pathogen genes into natural populations. Each of these mechanisms requires complex genetic engineering, and most are theoretically expected to permanently spread throughout the target species' geographical range. In the near term, risk issues and technical limits of molecular methods could delay the development and use of these mechanisms. We propose a gene-drive mechanism that can be self-limiting over time and space, and is simpler to build. This mechanism involves one gene that codes for toxicity (killer) and a second that confers immunity to the toxic effects (rescue). We use population-genetic models to explore cases with one or two independent insertions of the killer gene and one insertion of the rescue gene. We vary the dominance and penetrance of gene action, as well as the magnitude of fitness costs. Even with the fitness costs of 10 per cent for each gene, the proportion of mosquitoes expected to transmit the pathogen decreases below 5 per cent for over 40 generations after one 2 : 1 release (engineered : wild) or after four 1 : 2 releases. Both the killer and rescue genes will be lost from the population over time, if the rescue construct has any associated fitness cost. Molecular approaches for constructing strains are discussed. The Royal Society 2008-09-02 2008-12-22 /pmc/articles/PMC2572679/ /pubmed/18765342 http://dx.doi.org/10.1098/rspb.2008.0846 Text en Copyright © 2008 The Royal Society http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Gould, Fred
Huang, Yunxin
Legros, Mathieu
Lloyd, Alun L
A Killer–Rescue system for self-limiting gene drive of anti-pathogen constructs
title A Killer–Rescue system for self-limiting gene drive of anti-pathogen constructs
title_full A Killer–Rescue system for self-limiting gene drive of anti-pathogen constructs
title_fullStr A Killer–Rescue system for self-limiting gene drive of anti-pathogen constructs
title_full_unstemmed A Killer–Rescue system for self-limiting gene drive of anti-pathogen constructs
title_short A Killer–Rescue system for self-limiting gene drive of anti-pathogen constructs
title_sort killer–rescue system for self-limiting gene drive of anti-pathogen constructs
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2572679/
https://www.ncbi.nlm.nih.gov/pubmed/18765342
http://dx.doi.org/10.1098/rspb.2008.0846
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