Drosophila melanogaster as a Model for Gene Drive Systems
Drosophila melanogaster as a Model for Gene Drive Systems
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DOI：
10.1079/9781800621176.0009
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发表时间：
2022-01-01
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影响因子：
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通讯作者：
Champer, Jackson
中科院分区：
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作者：
Champer, Jackson
工程基因驱动等位基因被设计成偏向遗传，增加其在群体中的频率（图9.1）（Esvelt等人，2014;Bull, 2015； Gantz和Bier， 2015）； Champer等人，2016；Carballar-Lejarazú和James, 2017； Macias等人，2017；Burt和Crisanti, 2018； Leftwich等人，2018；Quinn和Nolan, 2020； Hay等人，2021)。如果它们的效率足够高，这种驱动可以通过释放一些个体到自然群体中来启动驱动等位基因的传播来用于修饰或抑制。基因驱动的潜在应用是广泛的，包括预防蚊子或其他病媒中的疾病传播，通常是通过使用作为驱动的效应成分的附加“有效载荷”或“货物”基因。它们还可以用来抑制威胁生态系统稳定的入侵物种等种群（Dearden等人，2017；Teem等人，2020），甚至是农业害虫（Scott等人，2018）。当降低病媒传播疾病（Jones et al., 2021）和入侵物种（Dearden et al., 2017）发病率的努力陷入停滞时，基因驱动可能会提供一种非常有效且廉价的替代方案。在其他情况下，与涉及杀虫剂或诱捕的方法相比，基因驱动方法可能更环保或更合乎道德。要使基因驱动发挥作用，必须克服几个挑战。有些是社会政治性质的，研究人员也面临着一系列令人生畏的技术挑战。例如，由驱动本身形成的抗性等位基因可以阻止驱动的传播。驱动适应性成本可能由驱动成分的表达或必要基因的不期望切割引起，也可能降低驱动速度并阻止成功的结果。另一方面，某些类型的驱动可以无限制地在一个物种中传播，即使只有某些种群应该作为目标。基因驱动的许多可能应用涉及昆虫，模式生物，黑腹果蝇，很好地成为基因驱动策略的试验台，旨在克服这些挑战。事实上，到目前为止，大多数形式的基因驱动已经在果蝇身上进行了测试和开发（表9.1），通常都是成功的。在这里，我们研究了这些驱动及其在D. melanogaster中的实验演示，重点研究了开发高效基因驱动系统的机制和经验教训。
Engineered gene drive alleles are designed to bias inheritance, increasing their frequency in a population (Fig. 9.1)(Esvelt et al., 2014; Bull, 2015; Gantz and Bier, 2015a; Champer et al., 2016; Carballar-Lejarazú and James, 2017; Macias et al., 2017; Burt and Crisanti, 2018; Leftwich et al., 2018; Quinn and Nolan, 2020; Hay et al., 2021). If their efficiency is sufficiently high, such drives could be used for modification or suppression by releasing a few individuals into natural populations to initiate the spread of the drive allele. Potential applications for gene drives are broad and include preventing disease transmission in mosquitoes or other vectors, often through use of attached ‘payload’or ‘cargo’genes that serve as the effector component of a drive. They could also be used to suppress populations such as invasive species where they are threatening ecosystem stability (Dearden et al., 2017; Teem et al., 2020) or even agricultural pests (Scott et al., 2018). When efforts to reduce the incidence of vector-borne disease (Jones et al., 2021) and invasive species (Dearden et al., 2017) are stalled, gene drives could potentially offer a highly effective and inexpensive alternative. In other situations, a gene drive approach could be more environmentally friendly or ethical compared with methods involving pesticides or trapping. For gene drives to be useful, several challenges must be overcome. Some are socio-political in nature and researchers are also faced with a daunting array of technical challenges. For example, resistance alleles formed by the drive itself can halt the spread of the drive. Drive fitness costs, which can be caused by expression of drive components or undesired cleavage of essential genes, could also reduce drive speed and prevent successful outcomes. On the other hand, some types of drives could spread without limit through a species, even if only certain populations should be targeted. With many possible applications of gene drives involving insects, the model organism, Drosophila melanogaster, is well placed to be a test bed for gene drive strategies that are designed to overcome these challenges. Indeed, most forms of gene drive thus far have been tested and developed in the fruit fly (Table 9.1), often successfully. Here, we examine each of these drives and their experimental demonstrations in D. melanogaster, focusing on mechanisms and lessons learned for developing high-efficiency gene drive systems.