Chromosomal Rearengements in Aedes aegypti - Modified Project Summary/Abstract Section Aedes aegypti transmits several arboviral diseases, including dengue and Zika fever, which threaten virtually half of the world’s human population. Two subspecies, Ae. aegypti aegypti (Aaa) and Ae. aegypti formosus (Aaf), have been described based on their body coloration. These subspecies differ remarkably from each other in their worldwide distribution, association with humans, and ability to transmit pathogens. In Anopheles populations, polymorphic inversions are often responsible for epidemiologically important phenotypes but our knowledge about chromosomal rearrangements in Aedes populations is limited. Although our recent study identifies a large pool of structural variation in the Ae. aegypti genome, their impact on behavior and adaptations of this species remains completely unknown. We hypothesize that chromosomal inversions contribute to the remarkable phenotypic and genetic plasticity of Ae. aegypti. However, more studies are needed to better understand the geographical patterns of the inversion distribution all over the globe and their potential involvement in ecotypic differentiations of the Ae. aegypti subspecies. Our project will test whether chromosomal rearrangements are 1) subspecies specific; 2) associated with ecological variables in Africa; 3) involved in mosquito adaptations to human. In this study, we will take advantage of the improved, fully re-annotated genome assembly for Ae. aegypti, employ the Hi-C approach and SNP-based inversion genotyping in publicly available WGS sequencing data to characterize chromosomal rearrangements across the world-wide distribution. We will also apply simple and robust PCR-based approaches to identify presence of common African inversions in individual mosquitoes in Senegal and use RNA-seq to determine differences in transcriptional profiles of standard and inverted genotypes. Our long-term goal is to understand the underlying genomic determinants of epidemiologically important phenotypic and behavioral differentiation of Ae. aegypti mosquitoes. Toward this end, we propose three specific aims: 1) identify patterns of world-wide distribution of the chromosomal rearrangements in Ae. aegypti and their associations with Ae. aegypti subspecies; 2) test if widely spread chromosomal inversions are associated with ecological variables in Africa; 3) determine specific transcriptional profiles associated with standard and inverted homokaryotypes of common African inversion 1pA. The discovery of chromosomal inversions in Ae. aegypti will stimulate future genetic studies aimed at preventing mosquito-borne disease transmission
