Discovery of Point Mutations in the Voltage-Gated Sodium Channel from African Aedes aegypti Populations: Potential Phylogenetic Reasons for Gene Introgression

Abstract

BackgroundYellow fever is endemic in some countries in Africa, and Aedes aegpyti is one of the most important vectors implicated in the outbreak. The mapping of the nation-wide distribution and the detection of insecticide resistance of vector mosquitoes will provide the beneficial information for forecasting of dengue and yellow fever outbreaks and effective control measures.Methodology/Principal FindingsHigh resistance to DDT was observed in all mosquito colonies collected in Ghana. The resistance and the possible existence of resistance or tolerance to permethrin were suspected in some colonies. High frequencies of point mutations at the voltage-gated sodium channel (F1534C) and one heterozygote of the other mutation (V1016I) were detected, and this is the first detection on the African continent. The frequency of F1534C allele and the ratio of F1534C homozygotes in Ae. aegypti aegypti (Aaa) were significantly higher than those in Ae. aegypti formosus (Aaf). We could detect the two types of introns between exon 20 and 21, and the F1534C mutations were strongly linked with one type of intron, which was commonly found in South East Asian and South and Central American countries, suggesting the possibility that this mutation was introduced from other continents or convergently selected after the introgression of Aaa genes from the above area.Conclusions/SignificanceThe worldwide eradication programs in 1940s and 1950s might have caused high selection pressure on the mosquito populations and expanded the distribution of insecticide-resistant Ae. aegypti populations. Selection of the F1534C point mutation could be hypothesized to have taken place during this period. The selection of the resistant population of Ae. aegypti with the point mutation of F1534C, and the worldwide transportation of vector mosquitoes in accordance with human activity such as trading of used tires, might result in the widespread distribution of F1534C point mutation in tropical countries.

Combined target site (kdr) mutations play a primary role in highly pyrethroid resistant phenotypes of Aedes aegypti from Saudi Arabia

“…While the 1534C mutation is widespread, our study contributes to knowledge of the boundaries for each of the V1016 mutations, with the most westerly report of the 1016G mutation to date. Interestingly, the 1016I mutation has recently been detected in Ghana [27], alongside the F1534C substitution, suggesting a possible contact zone between the 1016G and 1016I mutations located between Saudi Arabia and West Africa.…”

“…The vast majority of studies of resistance mechanisms in Ae. aegypti are from The Americas and Asia [19, 25, 26], though a recent first study from West Africa identified the presence of target site resistance shared with American populations [27]. Knowledge of resistance mechanisms in the Middle East and their relationship with other regions is currently lacking.…”

Sodium Channel Mutations and Pyrethroid Resistance in Aedes aegypti

“…Instead, mutation V1016I was found, and often coexists with F1534C in South and North America, such as Venezuela [48], three French overseas territories [49], Brazil [50,51,52], Mexico [53], and the USA [54]. More recently, V1016I and F1534C were detected in Ghana, Africa [55], and a new mutation, T1520I, was found along with the F1534C mutation in a population in India [56]. …”

“…More recently, V1016G, along with F1534C, was also detected in Ghana. Genomic sequence analysis suggests a possible migration event of mosquitoes carrying F1534C from South or North America to Africa [55]. …”

Heterogeneous genetic invasions of three insecticide resistance mutations in Indo-Pacific populations ofAedes aegypti(L.)

“…However, it is not clear if this variation reflects movement patterns of mosquitoes (genetic invasion) or ongoing mutation and selection. Evidence of resistance mutations spreading as mosquitoes move has been found in Ghana where mutation F1534C appeared, as a first record in Africa, associated with an intron phylogeny from Southeast Asia and South America (H. Kawada et al, 2016).…”