A Killer-Rescue system for self-limiting gene drive of anti-pathogen constructs
A Killer-Rescue system for self-limiting gene drive of anti-pathogen constructs
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DOI：
10.1098/rspb.2008.0846
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发表时间：
2008-12-22
影响因子：
4.7
通讯作者：
Lloyd, Alun L.
中科院分区：
文献类型：
--
作者：
Gould, Fred;Huang, Yunxin;Lloyd, Alun L.
已经提出了许多遗传机制来驱动抗病原体基因进入自然种群。这些机制中的每一个都需要复杂的基因工程，理论上，大多数机制都有望在目标物种的地理范围内永久传播。在短期内，分子方法的风险问题和技术限制可能会延迟这些机制的开发和使用。我们提出了一种基因驱动机制，可以在时间和空间上自我限制，并且更容易构建。这种机制涉及一个编码毒性（杀手）的基因和第二个赋予对毒性作用免疫力（救援）的基因。我们使用群体遗传学模型来探索具有一个或两个独立的杀伤基因插入和一个拯救基因插入的病例。我们改变了基因作用的优势和优势度，以及适应性成本的大小。即使每个基因的适应性成本为10%，在一次2：1释放（工程：野生）或四次1：2释放后，预计传播病原体的蚊子比例在40多代中下降到5%以下。如果拯救构建体有任何相关的适应度成本，那么随着时间的推移，杀手基因和拯救基因都会从种群中丢失。讨论了构建菌株的分子方法。
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.