Evidence for both sequential mutations and recombination in the evolution of kdr alleles in Aedes aegypti

Abstract

Background Aedes aegypti is a globally distributed vector of human diseases including dengue, yellow fever, chikungunya, and Zika. Pyrethroid insecticides are the primary means of controlling adult A. aegypti populations to suppress arbovirus outbreaks, but resistance to pyrethroid insecticides has become a global problem. Mutations in the voltage-sensitive sodium channel (Vssc) gene are a major mechanism of pyrethroid resistance in A. aegypti. Vssc resistance alleles in A. aegypti commonly have more than one mutation. However, our understanding of the evolutionary dynamics of how alleles with multiple mutations arose is poorly understood. Methodology/Principal findings We examined the geographic distribution and association between the common Vssc mutations (V410L, S989P, V1016G/I and F1534C) in A. aegypti by analyzing the relevant Vssc fragments in 25 collections, mainly from Asia and the Americas. Our results showed all 11 Asian populations had two types of resistance alleles: 1534C and 989P+1016G. The 1534C allele was more common with frequencies ranging from 0.31 to 0.88, while the 989P+1016G frequency ranged from 0.13 to 0.50. Four distinct alleles (410L, 1534C, 410L+1534C and 410L+1016I+1534C) were detected in populations from the Americas. The most common was 410L+1016I+1534C with frequencies ranging from 0.50 to 1.00, followed by 1534C with frequencies ranging from 0.13 to 0.50. Our phylogenetic analysis of Vssc supported multiple independent origins of the F1534C mutation. Our results indicated the 410L+1534C allele may have arisen by addition of the V410L mutation to the 1534C allele, or by a crossover event. The 410L+1016I+1534C allele was the result of one or two mutational steps from a 1534C background.

The F1534C voltage‐sensitive sodium channel mutation confers 7‐ to 16‐fold resistance to pyrethroid insecticides in Aedes aegypti

“…The 1534C allele is one of the most common kdr alleles in A. aegypti populations globally, and our results revealed that this allele confers 7–16 fold level of resistance to pyrethroids (Fig. ).…”

“…The 1534C and 989P+ 1016G alleles are widely distributed in Asian populations, but 1534C confers less pyrethroid resistance than the 989P+1016G allele (Fig. ).…”

“…The insecticide‐susceptible ROCK strain has been reared in laboratories without exposure to insecticides for decades. BKK and UBN were originally collected from Bangkok and Ubon Ratchathani, Thailand in 2018, respectively . These strains were pooled to obtain enough mosquitoes and chosen because they had a high frequency (>0.8) of the F1534C mutation.…”

“…To date, at least 11 Vssc mutations have been identified, individually or in combination, in A. aegypti populations. Alleles that have been identified are 410L, 982W, 1011V/M, 1016I/G, 1534C, 410L+1016I, 410L+1534C, 410L+1016I+1534C, 923V+1011M, 989P+1016G, 989P+1016G+1534C, 1011M+1016G, 1016I+1534C, 1016G+1534C, 1016G+1763Y and 1520I+1534C . Amino acid positions of these mutations are numbered based on the house fly VSSC (Genbank accession number: AAB47604).…”

Molecular Insight into the Knockdown Resistance (kdr) in the Voltage Gated Sodium Channel (vgsc) Gene of the Main Dengue Vector, Aedes aegypti (Diptera: Culicidae) and the Discovery of Novel Regional Specific Point Mutation A1007G in Malaysia.

“…An attempt was made by a research group from United States of America to investigate this mutation in the American population of Ae. aegypti [63]. Unfortunately, this mutation could not be detected from any samples, suggesting kdr allele A1007G, is a part of other geographic mutations similar to V410L [36]…”