Overexpression and nonsynonymous mutations of UDP-glycosyltransferases are potentially associated with pyrethroid resistance in Anopheles funestus

Talal Al-Yazeedi*, Abdullahi Muhammad, Helen Irving, Seung Joon Ahn, Jack Hearn, Charles S. Wondji

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

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    Abstract

    UDP-glycosyltransferases (UGTs) enzymes are pivotal in insecticide resistance by transforming hydrophobic substrates into more hydrophilic forms for efficient cell elimination. This study provides the first comprehensive investigation of Anopheles funestus UGT genes, their evolution, and their association with pyrethroid resistance. We employed a genome-wide association study using pooled sequencing (GWAS-PoolSeq) and transcriptomics on pyrethroid-resistant An. funestus, along with deep-targeted sequencing of UGTs in 80 mosquitoes Africa-wide. UGT310B2 was consistently overexpressed Africa-wide and significant gene-wise Fst differentiation was observed between resistant and susceptible populations: UGT301C2 and UGT302A3 in Malawi, and UGT306C2 in Uganda. Additionally, nonsynonymous mutations in UGT genes were identified. Gene-wise Tajima's D density curves provide insights into population structures within populations across these countries, supporting previous observations. These findings have important implications for current An. funestus control strategies facilitating the prediction of cross-resistance to other UGT-metabolised polar insecticides, thereby guiding more effective and targeted insecticide resistance management efforts.

    Original languageEnglish
    Article number110798
    JournalGenomics
    Volume116
    Issue number2
    Early online date29 Jan 2024
    DOIs
    Publication statusPrint publication - Mar 2024

    Bibliographical note

    Publisher Copyright:
    © 2024 The Authors

    Keywords

    • Genomics
    • Insecticide resistance
    • Target sequencing
    • Transcriptomics
    • UDP-glycosyltransferases
    • Vector control

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