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

这项研究将调查杀虫剂使用模式和蚊子运动在野生捕获的aedes aeygpti蚊子抗药性进化和传播中的相对作用。依赖大量使用杀虫剂的项目现在被用于控制。以杀虫剂为基础的控制策略的有效性正受到杀虫剂抗药性演变的威胁。抗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不清楚。杀虫剂的使用施加了一种选择压力，但这种压力在时间和空间上并不是恒定的。此外，随着蚊子种群的混合，蚊子可以将耐药性传播到新的地区。这些蚊子传播包括登革热、基孔肯雅热和寨卡病毒在内的多种病毒性疾病，是一个主要的公共卫生问题。这项研究将对杀虫剂抗药性管理产生显著的更广泛的影响，并将有助于开发新的蚊虫控制策略。埃及伊蚊最常见的抗药性形式是由对拟除虫菊酯类杀虫剂产生抗药性的类同源钠通道基因的点突变驱动的。这些点突变被命名为kdr，意思是“击倒抗性”，这些点突变可能会带来适应成本，使耐药个体在没有杀虫剂压力的情况下不太适应。城市杀虫剂使用地点和时间的不同造成了一个零星的环境，没有杀虫剂的避难所，易感蚊子可能获得健康优势，而有杀虫剂的地区，只有耐药蚊子才能生存。幼虫栖息地的质量也存在差异，这导致个体之间对资源的依赖密度的竞争。在这种复杂的选择情景下，基因类型的相对适合度可能会根据杀虫剂或幼虫密度的存在而变化。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式实验，以量化kdr基因型在两种不同处理的所有组合下的相对适合性：使用和不使用杀虫剂，以及高和低幼虫密度。这些实验将有助于理解埃及伊蚊kdr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时间和空间的模式。

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.