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Abstract Due to limitations in conventional disease vector control strategies including the rise of insecticide resistance in natural populations of mosquitoes, genetic control strategies using CRISPR gene drive systems have been under serious consideration. The identification of CRISPR target sites in mosquito populations is a key aspect for developing efficient genetic vector control strategies. While genome-wide Cas9 target sites have been explored in mosquitoes, a precise evaluation of target sites focused on coding sequence (CDS) is lacking. Additionally, target site polymorphisms have not been characterized for other nucleases such as Cas12a, which require a different DNA recognition site (PAM) and would expand the accessibility of mosquito genomes for genetic engineering. We undertook a comprehensive analysis of potential target sites for both Cas9 and Cas12a nucleases within the genomes of natural populations of Anopheles gambiae and Aedes aegypti from multiple continents. We demonstrate that using two nucleases increases the number of targets per gene. Also, we identified differences in nucleotide diversity between North American and African Aedes populations, impacting the abundance of good target sites with a minimal degree of polymorphisms that can affect the binding of gRNA. Lastly, we screened for gRNAs targeting sex-determination genes that could be widely applicable for developing field genetic control strategies. Overall, this work highlights the utility of employing both Cas9 and Cas12a nucleases and underscores the importance of designing universal genetic strategies adaptable to diverse mosquito populations.

Abstract Background Rapid adaptation to new environments can facilitate species invasions and range expansions. Understanding the mechanisms of adaptation used by invasive disease vectors in new regions has key implications for mitigating the prevalence and spread of vector-borne disease, although they remain relatively unexplored. Results Here, we integrate whole-genome sequencing data from 96 Aedes aegypti mosquitoes collected from various sites in southern and central California with 25 annual topo-climate variables to investigate genome-wide signals of local adaptation among populations. Patterns of population structure, as inferred using principal components and admixture analysis, were consistent with three genetic clusters. Using various landscape genomics approaches, which all remove the confounding effects of shared ancestry on correlations between genetic and environmental variation, we identified 112 genes showing strong signals of local environmental adaptation associated with one or more topo-climate factors. Some of them have known effects in climate adaptation, such as heat-shock proteins, which shows selective sweep and recent positive selection acting on these genomic regions. Conclusions Our results provide a genome wide perspective on the distribution of adaptive loci and lay the foundation for future work to understand how environmental adaptation in Ae. aegypti impacts the arboviral disease landscape and how such adaptation could help or hinder efforts at population control.

Abstract Background In the summer of 2013, Aedes aegypti Linnaeus was first detected in three cities in central California (Clovis, Madera and Menlo Park). It has now been detected in multiple locations in central and southern CA as far south as San Diego and Imperial Counties. A number of published reports suggest that CA populations have been established from multiple independent introductions. Results Here we report the first population genomics analyses of Ae. aegypti based on individual, field collected whole genome sequences. We analyzed 46 Ae. aegypti genomes to establish genetic relationships among populations from sites in California, Florida and South Africa. Based on 4.65 million high quality biallelic SNPs, we identified 3 major genetic clusters within California; one that includes all sample sites in the southern part of the state (South of Tehachapi mountain range) plus the town of Exeter in central California and two additional clusters in central California. Conclusions A lack of concordance between mitochondrial and nuclear genealogies suggests that the three founding populations were polymorphic for two main mitochondrial haplotypes prior to being introduced to California. One of these has been lost in the Clovis populations, possibly by a founder effect. Genome-wide comparisons indicate extensive differentiation between genetic clusters. Our observations support recent introductions of Ae. aegypti into California from multiple, genetically diverged source populations. Our data reveal signs of hybridization among diverged populations within CA. Genetic markers identified in this study will be of great value in pursuing classical population genetic studies which require larger sample sizes.