A Synthetic Gene Drive System for Local, Reversible Modification and Suppression of Insect Populations
A Synthetic Gene Drive System for Local, Reversible Modification and Suppression of Insect Populations
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DOI：
10.1016/j.cub.2013.02.059
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发表时间：
2013-04-22
期刊：
影响因子：
9.2
通讯作者：
Hay, Bruce A.
中科院分区：
文献类型：
--
作者：
Akbari, Omar S.;Matzen, Kelly D.;Hay, Bruce A.
用不能传播疾病的转基因个体替代野生昆虫种群提供了一种自我延续的疾病预防方法，但需要基因驱动机制将这些特征传播到高频率[1-3]。要求转基因超过阈值频率以便传播的驱动机制是有吸引力的，因为它们带来局部而不是全局替换，并且转基因可以通过用野生型个体稀释群体来消除[4-6]。这些特征在许多社会和监管环境中可能很重要[7-10]。在这里，我们描述了第一个创建的合成阈值依赖性基因驱动系统，指定的母源效应致死性欠显性（UDMEL），其中两个母系表达的毒素，位于不同的染色体上，每个连接合子解毒剂能够拯救其他毒素的母源效应致死性。我们证明了阈值依赖的替代在果蝇的单和两个位点的配置。模型表明，转基因的传播往往局限于当地环境。他们还表明，在已经进行单基因座UDMEL的群体中，重复释放野生型雄性可能导致群体抑制，这是一种新的遗传群体操纵方法。
Replacement of wild insect populations with genetically modified individuals unable to transmit disease provides a self-perpetuating method of disease prevention but requires a gene drive mechanism to spread these traits to high frequency [1-3]. Drive mechanisms requiring that transgenes exceed a threshold frequency in order to spread are attractive because they bring about local but not global replacement, and transgenes can be eliminated through dilution of the population with wild-type individuals [4-6]. These features are likely to be important in many social and regulatory contexts [7-10]. Here we describe the first creation of a synthetic threshold-dependent gene drive system, designated maternal-effect lethal underdominance (UDMEL), in which two maternally expressed toxins, located on separate chromosomes, are each linked with a zygotic antidote able to rescue maternal-effect lethality of the other toxin. We demonstrate threshold-dependent replacement in single- and two-locus configurations in Drosophila. Models suggest that transgene spread can often be limited to local environments. They also show that in a population in which single-locus UDMEL has been carried out, repeated release of wild-type males can result in population suppression, a novel method of genetic population manipulation.