Target site (knockdown resistance) gene mutations and population genetic structure of Aedes aegypti in Saudi Arabia

Abstract

Aedes aegypti is the primary vector for dengue, chikungunya, yellow fever and, more recently, Zika viruses worldwide. Aedes aegypti is well established today all over the world. The first record of Ae. aegypti in southwestern Saudi Arabia was in 1956. However, the first outbreak and cases of dengue fever in Saudi Arabia were reported in 1994, and cases have increased in recent years. In Chapters 3 and 4, I collected field populations from five regions of south and southwestern Saudi Arabia. In chapter 3, I genotyped and determined the frequency of known kdr mutations in domains IIS6 and IIIS6 of the vgsc gene using polymerase chain reaction (PCR) amplification and sequencing. I estimated the frequency of kdr mutations and genotypes from Saudi Arabia as well as from other countries, Thailand, Myanmar (Southeast Asia) and Uganda (East Africa). I constructed haplotype networks to infer the evolutionary relationships of these gene regions. In chapter 4, I used seventeen microsatellite markers from previously published studies to determine the genetic population structure and test for dispersal and gene flow within the five regions of Saudi Arabia. In chapter 3, the three known kdr mutations, S989P, V1016G (IIS6) and F1534C (IIIS6), were detected in all five regions of Saudi Arabia. Interestingly, I detected that the Ae. aegypti populations in Saudi Arabia still carry the triple homozygous wild type genotype in two individuals from the highlands of the Jazan region and one from Al Quoz, Sahil. Overall, nine genotypes comprising four haplotypes were observed in Saudi Arabia. The median-joining haplotype networks of eight populations from Saudi Arabia, Southeast Asia and East Africa for both the IIS6 and IIIS6 domains revealed that haplotype diversity was highest in Uganda and in the Jazan and Sahil regions of Saudi Arabia, whereas haplotype diversity was low in the Jeddah, Makkah and Madinah regions. Median- joining haplotype networks of both domains indicated selection acting on the kdr-mutation containing haplotypes in Saudi Arabia due to the high frequency of haplotypes that contained these mutations. In chapter 4, we found high passive or long-distance dispersal capability in Ae. aegypti from Saudi Arabia, possibly through road connectivity and human activities. African ancestry was present in the highland area of the Jazan region and the lowland of Jazan and Sahil. There are two main genetic clusters in Saudi Arabia. The Jazan highland population which clusters with Uganda (from Zika forest), while Western Saudi Arabia populations (Makkah, Jeddah, and Madinah), including Najran, cluster with Thailand. The ABC analysis indicates a high signal of admixture in Aedes aegypti from Saudi Arabia involving both African and out-of-African populations. This is the first comprehensive study on the population genetics of Ae. aegypti from the Arabian Peninsula. The presence of wild type haplotypes without any of the three kdr mutations, i.e. that are fully susceptible, in Saudi Arabia in chapter 3 indicates that further consideration should be given to insecticide resistance management strategies that could restore pyrethroid sensitivity to the populations of Ae. aegypti in Saudi Arabia as part of an integrative vector control strategy. The results presented in chapter 4 should be taken into account when designing vector control strategies, such as potential future trials of Wolbachia releases for dengue control.

Date of Award	1 Aug 2023
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Catherine Walton (Supervisor)