Harnessing Wolbachia cytoplasmic incompatibility alleles for confined gene drive: A modeling study.

Harnessing Wolbachia cytoplasmic incompatibility alleles for confined gene drive: A modeling study.
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DOI:
10.1371/journal.pgen.1010591
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发表时间:
2023-01
期刊:
影响因子:
4.5
通讯作者:
--
中科院分区:
生物学2区
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沃尔巴克氏体是一种母体遗传的细菌,可以通过操纵繁殖在种群中迅速传播。cifA和cifB是在沃尔巴克氏体噬菌体中发现的基因,它们负责细胞质不相容,这是沃尔巴克氏体最常见的生殖干扰类型。在这种现象中,当同时具有cifA和cifB的雄性(或在某些系统中仅具有cifB)与缺乏cifA的雌性交配时,不会产生可存活的后代。利用这一特性,我们提出了一种新型的毒素解毒剂基因驱动,这种基因驱动可以只用昆虫基因组中的这两个基因来构建,而不是整个沃尔巴克氏菌。通过数学模型和仿真模型,我们发现含有cifA和cifB的驱动器共同创建了一个具有中等到高引入阈值的受限驱动器。当单独引入时,它们就像一个自我限制的驱动器。我们观察到,这些驱动器的性能在很大程度上受到各种生态参数和驱动器特性的影响。将我们的模型扩展到连续空间,我们发现驱动个体释放分布对驱动持久性有关键影响。我们的研究结果表明,这些基于沃尔巴克氏体转基因的新型驱动器是安全灵活的群体遗传修饰候选者。沃尔巴克氏菌可以被放入昆虫体内并释放到野外,在那里沃尔巴克氏菌在昆虫种群中传播。它们已被用作有效的疾病控制工具,因为沃尔巴克氏体减少了蚊子传播病原体的机会。也有可能利用沃尔巴克氏体传播机制来推动基因驱动,从而允许在昆虫种群中灵活地部署货物基因。我们使用数学反应-扩散模型来评估使用沃尔巴克氏体噬菌体基因cifA和cifB作为基因驱动的可能性。在这个系统中,这些基因被直接插入到昆虫的基因组中,除非雌性也有驱动等位基因,否则它们将无法与驱动雄性生育后代。我们在简单泛群和连续空间群的一系列性能参数下对其特性进行了建模。总的来说,我们发现我们的CifAB驱动可以高度局限于目标种群,但为昆虫物种的种群改造提供了一个强大的选择。
Wolbachia are maternally-inherited bacteria, which can spread rapidly in populations by manipulating reproduction. cifA and cifB are genes found in Wolbachia phage that are responsible for cytoplasmic incompatibility, the most common type of Wolbachia reproductive interference. In this phenomenon, no viable offspring are produced when a male with both cifA and cifB (or just cifB in some systems) mates with a female lacking cifA. Utilizing this feature, we propose new types of toxin-antidote gene drives that can be constructed with only these two genes in an insect genome, instead of the whole Wolbachia bacteria. By using both mathematical and simulation models, we found that a drive containing cifA and cifB together creates a confined drive with a moderate to high introduction threshold. When introduced separately, they act as a self-limiting drive. We observed that the performance of these drives is substantially influenced by various ecological parameters and drive characteristics. Extending our models to continuous space, we found that the drive individual release distribution has a critical impact on drive persistence. Our results suggest that these new types of drives based on Wolbachia transgenes are safe and flexible candidates for genetic modification of populations. Wolbachia bacteria can be placed into insects and released into the wild, where the Wolbachia spreads throughout the insect population. They have been used as an effective disease control tool because the Wolbachia reduces transmission of pathogens by mosquitoes. It may also be possible to use the Wolbachia spread mechanism to power a gene drive, allowing for flexible deployment of cargo genes in insect populations. We used a mathematical reaction-diffusion model to assess the possibility of using Wolbachia phage genes cifA and cifB as a gene drive. In this system, these genes are inserted directly into the insect genome, and females will fail to have offspring with drive males unless they also have a drive allele. We model its characteristics under a range of performance parameters in both simple panmictic populations and continuous space populations. Overall, we find that our CifAB drive can be highly confined to a target population, yet provides a powerful option for population modification of insect species.
释放不兼容的男性在澳大利亚的野生和沃尔巴契亚岛伊德斯埃及埃及埃及的人群中进行了强烈的抑制。
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