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Modeling the Dynamics of a Non-Limited and a Self-Limited Gene Drive System in Structured Aedes aegypti Populations

机译：模拟埃及伊蚊种群中非限制性和自我限制性基因驱动系统的动力学

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Recently there have been significant advances in research on genetic strategies to control populations of disease-vectoring insects. Some of these strategies use the gene drive properties of selfish genetic elements to spread physically linked anti-pathogen genes into local vector populations. Because of the potential of these selfish elements to spread through populations, control approaches based on these strategies must be carefully evaluated to ensure a balance between the desirable spread of the refractoriness-conferring genetic cargo and the avoidance of potentially unwanted outcomes such as spread to non-target populations. There is also a need to develop better estimates of the economics of such releases. We present here an evaluation of two such strategies using a biologically realistic mathematical model that simulates the resident Aedes aegypti mosquito population of Iquitos, Peru. One strategy uses the selfish element Medea, a non-limited element that could permanently spread over a large geographic area; the other strategy relies on Killer-Rescue genetic constructs, and has been predicted to have limited spatial and temporal spread. We simulate various operational approaches for deploying these genetic strategies, and quantify the optimal number of released transgenic mosquitoes needed to achieve definitive spread of Medea-linked genes and/or high frequencies of Killer-Rescue-associated elements. We show that for both strategies the most efficient approach for achieving spread of anti-pathogen genes within three years is generally to release adults of both sexes in multiple releases over time. Even though females in these releases should not transmit disease, there could be public concern over such releases, making the less efficient male-only release more practical. This study provides guidelines for operational approaches to population replacement genetic strategies, as well as illustrates the use of detailed spatial models to assist in safe and efficient implementation of such novel genetic strategies.
机译：最近，在控制病媒昆虫种群的遗传策略研究方面取得了重大进展。其中一些策略利用自私遗传元件的基因驱动特性将物理连接的抗病原体基因传播到局部载体种群中。由于这些自私因素有可能在人群中传播，因此，必须仔细评估基于这些策略的控制方法，以确保在赋予耐火性的遗传货物的理想传播与避免潜在的不良后果（例如传播至非传染性疾病）之间取得平衡。目标人群。还需要对这种释放的经济性进行更好的估计。在这里，我们使用生物学上真实的数学模型对两种此类策略进行评估，该数学模型可模拟秘鲁伊基托斯的埃及伊蚊的种群。一种策略是使用自私的元素美狄亚（Medea），这是一种不受限制的元素，可以永久地散布在较大的地理区域内；另一种策略依赖于Killer-Rescue基因构建，并且据预测其时空分布有限。我们模拟了部署这些遗传策略的各种操作方法，并量化了实现与美狄亚相关的基因的定性传播和/或与杀手救援相关的元素的高频率所需的已释放转基因蚊子的最佳数量。我们表明，对于这两种策略，在三年内实现抗病原体基因传播的最有效方法通常是随着时间的推移以多次释放的方式释放成年男女。即使这些释放中的雌性不应该传播疾病，也可能引起公众对此类释放的关注，这使得效率较低的仅雄性释放更为实用。这项研究为种群替代遗传策略的操作方法提供了指南，并举例说明了使用详细的空间模型来帮助安全有效地实施这种新颖的遗传策略。

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