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nanos-Driven expression of piggyBac transposase induces mobilization of a synthetic autonomous transposon in the malaria vector mosquito Anopheles stephensi

机译:纳米驱动piggyBac转座酶的表达诱导疟疾媒介蚊(按蚊按蚊)中合成的自主转座子的动员

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摘要

Transposons are a class of selfish DNA elements that can mobilize within a genome. If mobilization is accompanied by an increase in copy number (replicative transposition), the transposon may sweep through a population until it is fixed in all of its interbreeding members. This introgression has been proposed as the basis for drive systems to move genes with desirable phenotypes into target species. One such application would be to use them to move a gene conferring resistance to malaria parasites throughout a population of vector mosquitos. We assessed the feasibility of using the piggyBac transposon as a gene-drive mechanism to distribute anti-malarial transgenes in populations of the malaria vector, Anopheles stephensi. We designed synthetic gene constructs that express the piggyBac transposase in the female germline using the control DNA of the An. stephensi nanos orthologous gene linked to marker genes to monitor inheritance. Two remobilization events were observed with a frequency of one every 23 generations, a rate far below what would be useful to drive anti-pathogen transgenes into wild mosquito populations. We discuss the possibility of optimizing this system and the impetus to do so.
机译:转座子是可以在基因组内动员的一类自私的DNA元素。如果动员伴随着拷贝数的增加(复制性转座),则转座子可能会席卷整个种群,直到它固定在其所有杂交成员中。已经提出这种渗入作为驱动系统将具有所需表型的基因移入靶物种的基础。一种这样的应用将是使用它们来在整个媒介蚊子种群中移动一个赋予抗疟原虫抗性的基因。我们评估了使用piggyBac转座子作为基因驱动机制在疟疾媒介按蚊(Anopheles stephensi)人群中分布抗疟疾转基因的可行性。我们设计了合成基因构建体,使用An的对照DNA在雌性种系中表达piggyBac转座酶。 stephensi nanos直系同源基因与标记基因相连,以监控遗传。观察到两次复活事件,每23代发生一次,其发生率远低于将抗病原体转基因驱动到野生蚊子种群中的有用率。我们讨论了优化此系统的可能性以及这样做的动力。

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