Evolution and coevolution of invasive Anopheles stephensi and sympatric Plasmodium populations in Africa: A genomic investigation - ABSTRACT Anopheles stephensi, a mosquito capable of spreading malaria, is a major threat to the progress of malaria control. It is a native vector in South Asia and portions of the Middle East but was reported in Djibouti in 2013 and is now well established throughout East Africa. This invasive vector is a threat to malaria control because it has the capacity thrive in both urban and rural areas. In addition, insecticide resistance has been reported across several portions of the invasive range. Most recently, An. stephensi has been the cause of malaria outbreaks in historically low transmission regions. There are critical knowledge gaps related to An. stephensi adaptation to the environment that facilitated its spread and establishment, and the genomic features that facilitate the compatibility with local Plasmodium falciparum strains. The goal of the proposed study is to identify the genomic bases of adaptation in invasive An. stephensi in Africa and An. stephensi’s susceptibility to local African P. falciparum strains. In addition, we will use these data to develop surveillance tools to better predict An. stephensi’s impact on malaria epidemiology. This project will continue our long-standing collaborations with academic and public health institutions in the US, Ethiopia, and Somalia. Ultimately, growing our understanding of the genomic diversity of An. stephensi will provide the bases for enhanced molecular surveillance and understanding of risk for future malaria outbreaks across the invasion range. Our specific aims are: 1) Evaluate the evolution and spread of An. stephensi over the course of the invasion to identify environmental adaptations, 2) We will identify An. stephensi genomic features associated with P. falciparum infection. 3) Develop tools to improve the reporting of epidemiologically relevant genomic markers in An. stephensi. Overall, this multiregional and interdisciplinary collaborative effort will fill gaps related to invasive An. stephensi adaptation in East Africa. Our results will provide the scientific bases for approaches to control of this invasive mosquito and ultimately the prevention of malaria.