Fine-scale adaptive divergence of<i>Aedes aegypti</i>in heterogeneous landscapes and among climatic conditions in Metropolitan Manila, Philippines

<jats:title>Abstract</jats:title><jats:p>The adaptive divergence of<jats:italic>Aedes aegypti</jats:italic>populations to heterogeneous environments may be a driving force behind the recent expansion of their habitat distribution and outbreaks of dengue disease in urbanized areas. In this study, we investigated the population genomics of<jats:italic>Ae. aegypti</jats:italic>at a regional scale in Metropolitan Manila, Philippines using double digestion restriction-site association DNA sequencing (ddRAD-Seq). Specifically, we used a Pool-Seq approach to generate a high number of single nucleotide polymorphisms (SNPs), which were used to determine local adaptation and population structure. We detected 65,473 SNPs in 217<jats:italic>Ae. aegypti</jats:italic>individuals from 14 populations with 76 non-neutral SNP loci. Additionally, 57 of these non-neutral SNP loci were associated with 8 landscape variables (e.g., open space, forest, etc) and 4 climate variables (e.g., air temperature, humidity, etc). Furthermore, the percentage of the area of landscape variables, such as forest, parks and recreation, air temperature, man-made building, and open space per local population was frequently associated with non-neutral SNP loci. Most non-neutral SNP loci formed four clusters that were in linkage disequilibrium with each other in physical proximity on the chromosome and were associated with a common environmental variable. Male and female populations exhibited contrasting spatial divergence, i.e., males exhibited greater divergence, likely reflecting their different dispersal abilities. In comparative analysis of the same<jats:italic>Ae. aegypti</jats:italic>individuals, the pairwise<jats:italic>F</jats:italic><jats:sub>ST</jats:sub>values of 11 microsatellite markers were lower than those of neutral SNP loci, indicating that the neutral SNP loci generated via ddRAD-Seq were more sensitive in terms of detecting genetic differences between populations at fine-spatial scales. Overall, this study demonstrates the utility of ddRAD-Seq for examining genetic differences in<jats:italic>Ae. aegypti</jats:italic>populations, and our data on mosquito dispersal at a regional spatial scale could inform vector control programs.</jats:p><jats:sec><jats:title>Author Summary</jats:title><jats:p>The population expansion of dengue vector,<jats:italic>Aedes aegypti</jats:italic>mosquitoes is one of the factors that may promote the outbreak of the diseases. Understanding the population genomics of<jats:italic>Ae.aegypti</jats:italic>may contribute to better knowledge about mosquito expansion and how they can adapt to the change in environment. In this study, we used pool-based ddRAD-Seq (Double Digest Restriction site Association DNA Sequencing) to generate SNPs that occur between the<jats:italic>Ae.aegypti</jats:italic>populations in Metropolitan Manila, Philippines. We found that non-neutral SNP loci are frequently associated with landscape variables compared to climatic variables. Landscape variables such as forest, park and recreation, air temperature, man-made building and open space are more frequently associated with non-neutral SNPs loci. Those landscape variables may relate to the mosquito’s fitness, therefore, induce the adaptive divergence within<jats:italic>Ae.aegypti</jats:italic>population. We also found male and female populations are exhibiting a contrast spatial divergence by using neutral SNP loci. In addition, neutral SNPs loci showed higher resolution in population structuring than microsatellite markers using the same individuals.</jats:p></jats:sec>