Evolution of kdr haplotypes in worldwide populations of Aedes aegypti: Independent origins of the F1534C kdr mutation

• Published in: PLoS neglected tropical diseases 2020-04, Vol.14 (4), p.e0008219
• Main Authors: Cosme, Luciano Veiga, Gloria-Soria, Andrea, Caccone, Adalgisa, Powell, Jeffrey Robert, Martins, Ademir Jesus
• Format: Article
• Language: English
• Subjects: Aedes - drug effects; Aedes - genetics; Aedes - virology; Aedes aegypti; Africa; Alleles; Animals; Aquatic insects; Asia; Australia; Biology and Life Sciences; Chikungunya Fever - prevention & control; Chikungunya Fever - transmission; DDT; Dengue; Dengue - prevention & control; Dengue - transmission; Dengue fever; Deoxyribonucleic acid; Disease outbreaks; DNA; DNA - genetics; Fever; Funding; Gene Frequency; Gene mutation; Genes; Genes, Insect; Genetic aspects; Genetic research; Genotype; Geographical distribution; Haplotypes; Human diseases; Insect populations; Insecticide resistance; Insecticide Resistance - genetics; Insecticides; Medicine and Health Sciences; Mosquito Vectors - genetics; Mosquito Vectors - virology; Mosquitoes; Mutation; Natural history; North America; Origins; People and places; Phylogeny; Physical Sciences; Population; Populations; Pyrethrins; Pyrethroids; Samples; Segments; Sodium; Sodium channels (voltage-gated); Submarine pipelines; Tropical diseases; Vector-borne diseases; Yellow fever; Yellow Fever - prevention & control; Yellow Fever - transmission; Yellow fever mosquito; Zika Virus Infection - prevention & control; Zika Virus Infection - transmission
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0008219

Aedes aegypti is the primary vector of dengue, chikungunya, Zika, and urban yellow fever. Insecticides are often the most effective tools to rapidly decrease the density of vector populations, especially during arbovirus disease outbreaks. However, the intense use of insecticides, particularly pyrethroids, has selected for resistant mosquito populations worldwide. Mutations in the voltage gated sodium channel (NaV) are among the principal mechanisms of resistance to pyrethroids and DDT, also known as "knockdown resistance," kdr. Here we report studies on the origin and dispersion of kdr haplotypes in samples of Ae. aegypti from its worldwide distribution. We amplified the IIS6 and IIIS6 NaV segments from pools of Ae. aegypti populations from 15 countries, in South and North America, Africa, Asia, Pacific, and Australia. The amplicons were barcoded and sequenced using NGS Ion Torrent. Output data were filtered and analyzed using the bioinformatic pipeline Seekdeep to determine frequencies of the IIS6 and IIIS6 haplotypes per population. Phylogenetic relationships among the haplotypes were used to infer whether the kdr mutations have a single or multiple origin. We found 26 and 18 haplotypes, respectively for the IIS6 and IIIS6 segments, among which were the known kdr mutations 989P, 1011M, 1016I and 1016G (IIS6), 1520I, and 1534C (IIIS6). The highest diversity of haplotypes was found in African samples. Kdr mutations 1011M and 1016I were found only in American and African populations, 989P + 1016G and 1520I + 1534C in Asia, while 1534C was present in samples from all continents, except Australia. Based primarily on the intron sequence, IIS6 haplotypes were subdivided into two well-defined clades (A and B). Subsequent phasing of the IIS6 + IIIS6 haplotypes indicates two distinct origins for the 1534C kdr mutation. These results provide evidence of kdr mutations arising de novo at specific locations within the Ae. aegypti geographic distribution. In addition, our results suggest that the 1534C kdr mutation had at least two independent origins. We can thus conclude that insecticide selection pressure with DDT and more recently with pyrethroids is selecting for independent convergent mutations in NaV.