Novel Synthetic Medea Selfish Genetic Elements Drive Population Replacement in Drosophila; a Theoretical Exploration of Medea-Dependent Population Suppression
Novel Synthetic Medea Selfish Genetic Elements Drive Population Replacement in Drosophila; a Theoretical Exploration of Medea-Dependent Population Suppression
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DOI：
10.1021/sb300079h
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发表时间：
2014-12-01
影响因子：
4.7
通讯作者：
Hay, Bruce A.
中科院分区：
文献类型：
--
作者：
Akbari, Omar S.;Chen, Chun-Hong;Hay, Bruce A.
昆虫是植物、动物和人类疾病的媒介。用不能传播疾病的转基因个体取代野生昆虫种群提供了一种潜在的自我延续的疾病预防方法。种群更替需要基因驱动机制，以便在野生种群中传播介导疾病难治性的相关基因。我们之前报道了合成美狄亚自私遗传因子的创造，能够驱动果蝇的种群更替。这些元件使用microrna介导的myd88沉默，myd88是胚胎背-腹侧模式形成所需的母系表达基因，加上早期合子表达的拯救性转基因，从而产生基因驱动。美狄亚元素需要通过额外的机制发挥作用，以便能够执行种群替换周期和/或从种群中移除现有的转基因，使用传播的第二代元素，同时将第一代元素赶出种群。在这里，我们报道了两个新的合成美狄亚元件的合成和群体遗传行为，它们通过操纵参与细胞囊胚形成或Notch信号传导的信号通路来驱动群体更替，这表明在果蝇中美狄亚元件可以通过操纵多种信号通路来产生。我们还描述了与雌性不育相关的卵巢和早期胚胎的mRNA和小RNA变化。最后，我们使用模型来说明携带导致雌性滞育依赖性致死的基因的美狄亚元件如何被用于种群抑制。
Insects act as vectors for diseases of plants, animals, and humans. Replacement of wild insect populations with genetically modified individuals unable to transmit disease provides a potentially self-perpetuating method of disease prevention. Population replacement requires a gene drive mechanism in order to spread linked genes mediating disease refractoriness through wild populations. We previously reported the creation of synthetic Medea selfish genetic elements able to drive population replacement in Drosophila. These elements use microRNA-mediated silencing of myd88, a maternally expressed gene required for embryonic dorso-ventral pattern formation, coupled with early zygotic expression of a rescuing transgene, to bring about gene drive. Medea elements that work through additional mechanisms are needed in order to be able to carry out cycles of population replacement and/or remove existing transgenes from the population, using second-generation elements that spread while driving first-generation elements out of the population. Here we report the synthesis and population genetic behavior of two new synthetic Medea elements that drive population replacement through manipulation of signaling pathways involved in cellular blastoderm formation or Notch signaling, demonstrating that in Drosophila Medea elements can be generated through manipulation of diverse signaling pathways. We also describe the mRNA and small RNA changes in ovaries and early embryos associated from Medea-bearing females. Finally, we use modeling to illustrate how Medea elements carrying genes that result in diapause-dependent female lethality could be used to bring about population suppression.