A multi-omic meta-analysis reveals novel mechanisms of insecticide resistance in malaria vectors

Abstract Malaria control faces challenges from widespread insecticide resistance in major Anopheles species. This study, employing a cross-species approach, integrates RNA-Sequencing, whole-genome sequencing, and microarray data to elucidate drivers of insecticide resistance in Anopheles gambiae com...

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Main Authors: Sanjay C. Nagi, Victoria A. Ingham
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-025-08221-6
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author Sanjay C. Nagi
Victoria A. Ingham
author_facet Sanjay C. Nagi
Victoria A. Ingham
author_sort Sanjay C. Nagi
collection DOAJ
description Abstract Malaria control faces challenges from widespread insecticide resistance in major Anopheles species. This study, employing a cross-species approach, integrates RNA-Sequencing, whole-genome sequencing, and microarray data to elucidate drivers of insecticide resistance in Anopheles gambiae complex and An. funestus. Here we show an inverse relationship between genetic diversity and gene expression, with highly expressed genes experiencing stronger purifying selection. Gene expression clusters physically in the genome, revealing potential coordinated regulation, and we find that highly over-expressed genes are associated with selective sweep loci. We identify known and novel candidate insecticide resistance genes, enriched for metabolic, cuticular, and behavioural functioning. We also present AnoExpress, a Python package, and an online interface for user-friendly exploration of resistance candidate expression. Despite millions of years of speciation, convergent gene expression responses to insecticidal selection pressures are observed across Anopheles species, providing crucial insights for malaria vector control.
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spelling doaj-art-b7ffdaae64ac44c69e1b68a542b87d652025-08-20T03:48:15ZengNature PortfolioCommunications Biology2399-36422025-05-018111110.1038/s42003-025-08221-6A multi-omic meta-analysis reveals novel mechanisms of insecticide resistance in malaria vectorsSanjay C. Nagi0Victoria A. Ingham1Vector Biology Department, Liverpool School of Tropical MedicineCentre for Infectious Diseases, University Hospital Heidelberg, Medical Faculty, Heidelberg UniversityAbstract Malaria control faces challenges from widespread insecticide resistance in major Anopheles species. This study, employing a cross-species approach, integrates RNA-Sequencing, whole-genome sequencing, and microarray data to elucidate drivers of insecticide resistance in Anopheles gambiae complex and An. funestus. Here we show an inverse relationship between genetic diversity and gene expression, with highly expressed genes experiencing stronger purifying selection. Gene expression clusters physically in the genome, revealing potential coordinated regulation, and we find that highly over-expressed genes are associated with selective sweep loci. We identify known and novel candidate insecticide resistance genes, enriched for metabolic, cuticular, and behavioural functioning. We also present AnoExpress, a Python package, and an online interface for user-friendly exploration of resistance candidate expression. Despite millions of years of speciation, convergent gene expression responses to insecticidal selection pressures are observed across Anopheles species, providing crucial insights for malaria vector control.https://doi.org/10.1038/s42003-025-08221-6
spellingShingle Sanjay C. Nagi
Victoria A. Ingham
A multi-omic meta-analysis reveals novel mechanisms of insecticide resistance in malaria vectors
Communications Biology
title A multi-omic meta-analysis reveals novel mechanisms of insecticide resistance in malaria vectors
title_full A multi-omic meta-analysis reveals novel mechanisms of insecticide resistance in malaria vectors
title_fullStr A multi-omic meta-analysis reveals novel mechanisms of insecticide resistance in malaria vectors
title_full_unstemmed A multi-omic meta-analysis reveals novel mechanisms of insecticide resistance in malaria vectors
title_short A multi-omic meta-analysis reveals novel mechanisms of insecticide resistance in malaria vectors
title_sort multi omic meta analysis reveals novel mechanisms of insecticide resistance in malaria vectors
url https://doi.org/10.1038/s42003-025-08221-6
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