DISSERTATION RESEARCH: Migration-selection balance in the evolution of insecticide resistance in Aedes aegypti

本研究旨在探讨野外捕获的埃及伊蚊的抗药性进化与传播过程中，杀虫剂施药方式与蚊虫运动的相对关系。依靠大量使用杀虫剂的项目现在被用于控制。基于杀虫剂的控制策略的有效性正受到杀虫剂抗性演变的威胁。耐药性在全球范围内有所增加，但这种传播背后的机制在很大程度上仍然未知。杀虫剂的施用产生了一种选择压力，但这种压力在时间或空间上不是恒定的。此外，随着种群的混合，蚊子可以将抗药性传播到新的地区。这些蚊子是一个主要的公共卫生问题，因为它们传播多种病毒性疾病，包括登革热、基孔肯雅热和寨卡病毒。这项研究将具有显著的更广泛的影响，因为它将为杀虫剂耐药性管理提供信息，并将有助于制定新的蚊子控制策略。埃及伊蚊最常见的杀虫剂抗性形式是由准同源钠通道基因的点突变驱动的，该基因赋予对拟除虫菊酯杀虫剂的抗性。这些点突变被命名为kdr，意为“击倒抗性”，它们可能携带适应度成本，使抗性个体在没有杀虫剂压力的情况下不太适合。城市杀虫剂使用地点和时间的变化造成了无杀虫剂避难所的不均匀环境，在那里易感蚊子可能获得适应性优势，而在有杀虫剂的地区，只有耐药蚊子存活。幼虫栖息地的质量也存在差异，这导致个体之间对资源的密度依赖竞争。在这种复杂的选择情景下，基因型的相对适合度可能会根据杀虫剂或幼虫密度的存在而改变。为了更好地了解这些动态，研究人员将在半自然条件下进行笼子实验，以量化暴露于两种不同处理组合的kdr基因型的相对适合度：使用与不使用杀虫剂，以及高与低幼虫密度。这些实验将有助于了解kdr在埃及伊蚊中的选择动态，并有助于解释在野外种群中观察到的抗性频率随空间和时间的变化模式。

The study will investigate the relative roles of the pattern of insecticide applications and mosquito movement in the evolution and propagation of resistance in wild-caught Aedes aeygpti mosquitoes. Programs relying on heavy use of insecticides are now used for control. The effectiveness of insecticide-based control strategies is being threatened by the evolution of insecticide resistance. Resistance has increased globally yet the mechanisms behind this spread are still largely unknown. Insecticide application exerts a selection pressure, yet this pressure is not constant in time or space. Additionally, mosquitoes can spread resistance to new areas as populations mix. These mosquitos are a major public health problem as they transmit multiple viral diseases including dengue fever, chikungunya, and zika virus. The research will have notable broader impacts as it informs insecticide resistance management and will be helpful in developing novel mosquito control strategies.The most common form of insecticide resistance in Aedes aegypti is driven by point mutations in the para-orthologous sodium channel gene, which confers resistance to pyrethroid insecticides. Named kdr for "knock-down resistance", these point mutations may carry a fitness cost, rendering the resistant individuals less fit in the absence of insecticide pressure. Variation in the location and timing of urban insecticide applications creates a patchy environment of insecticide-free refuges, where susceptible mosquitoes may gain a fitness advantage, and areas with insecticide, where only resistant mosquitoes survive. There is also variation in the quality of larval habitats, which leads to density-dependent competition between individuals for resources. Under this complex selection scenario, the relative fitness of genotypes may change based on the presence of insecticide or larval density. To better understand these dynamics, researchers will conduct cage experiments under semi-natural conditions to quantify the relative fitness of kdr genotypes exposed to all combinations of two different treatments: with versus without insecticide, and high versus low larval density. These experiments will contribute to understanding the selection dynamics of kdr in Aedes aegypti and help explain patterns of resistance frequencies observed in field populations over space and time.