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Background <p>Insecticide resistance poses a significant challenge to malaria control, driven by diverse molecular mechanisms, whose distribution remains poorly characterized in Ethiopia. This study presents the first results using whole-genome sequence data of <i>Anopheles gambiae</i> from Ethiopia, confirming its presence in the western region of the country and expanding its known geographical distribution.</p> Methods <p>Analysis of single-nucleotide polymorphisms and copy number variants focussed on key target-site insecticide resistance genes, including the voltage-gated sodium channel (<i>Vgsc</i>), acetylcholinesterase-1 (<i>Ace-1</i>), the gamma-aminobutyric acid (<i>GABA</i>)-gated chloride channel (<i>Rdl</i>) gene, as well as metabolic resistance loci such as cytochrome P450s (<i>Cyp6m2, Cyp6aa/p</i>, <i>Cyp9k1</i>) and carboxylesterases (<i>Coeae2f</i>, <i>Coeae2–7g</i>).</p> Results <p>Genomic analysis revealed high frequencies of <i>Vgsc</i>-L995F (kdr-west) mutations, alongside amplifications at <i>Cyp6aa/p</i>, <i>Cyp9k1</i>, and <i>Gste2</i>. Notably, frequencies of <i>Vgsc</i> and <i>Gste2</i> variants exhibited differences on a local scale, while <i>Vgsc</i> and <i>Cyp9k1</i> variant frequencies also fluctuated seasonally. Findings highlight the need for site-specific monitoring on a fine temporal scale. Furthermore, genome-wide selection scans using phased haplotypes identified emerging signals of selection at loci with a potential link to insecticide resistance, including a signal spanning 2L:33,767,545–34,391,778, which expands the catalogue of candidate loci for functional validation.</p> Conclusions <p>Together, the presence of high frequencies of known insecticide resistance markers suggests that <i>An</i>. <i>gambiae</i> populations may be largely refractory to pyrethroids and moderately resistant to organophosphate (OPs) insecticides in western Ethiopia. Findings necessitate a better understanding of the <i>An. gambiae</i> geographical distribution in Ethiopia, accompanied by resistance-informed malaria control interventions targeting the vector.</p> Graphical Abstract <p></p>

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Genomic analysis reveals selection pressure and the emergence of molecular insecticide resistance in the malaria vector, Anopheles gambiae, from Western Ethiopia

  • 期刊论文

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  • 发表日期：

    2026年8月5日

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  • Fekadu Gemechu,
  • Kelly L. Bennett,
  • Sisay Dugassa,
  • Anastasia Hernandez-Koutoucheva,
  • Araya Eukubay,
  • Alistair Miles,
  • Deriba Abera,
  • Chris S. Clarkson,
  • Lemu Golassa

摘要

Background

Insecticide resistance poses a significant challenge to malaria control, driven by diverse molecular mechanisms, whose distribution remains poorly characterized in Ethiopia. This study presents the first results using whole-genome sequence data of Anopheles gambiae from Ethiopia, confirming its presence in the western region of the country and expanding its known geographical distribution.

Methods

Analysis of single-nucleotide polymorphisms and copy number variants focussed on key target-site insecticide resistance genes, including the voltage-gated sodium channel (Vgsc), acetylcholinesterase-1 (Ace-1), the gamma-aminobutyric acid (GABA)-gated chloride channel (Rdl) gene, as well as metabolic resistance loci such as cytochrome P450s (Cyp6m2, Cyp6aa/p, Cyp9k1) and carboxylesterases (Coeae2f, Coeae2–7g).

Results

Genomic analysis revealed high frequencies of Vgsc-L995F (kdr-west) mutations, alongside amplifications at Cyp6aa/p, Cyp9k1, and Gste2. Notably, frequencies of Vgsc and Gste2 variants exhibited differences on a local scale, while Vgsc and Cyp9k1 variant frequencies also fluctuated seasonally. Findings highlight the need for site-specific monitoring on a fine temporal scale. Furthermore, genome-wide selection scans using phased haplotypes identified emerging signals of selection at loci with a potential link to insecticide resistance, including a signal spanning 2L:33,767,545–34,391,778, which expands the catalogue of candidate loci for functional validation.

Conclusions

Together, the presence of high frequencies of known insecticide resistance markers suggests that An. gambiae populations may be largely refractory to pyrethroids and moderately resistant to organophosphate (OPs) insecticides in western Ethiopia. Findings necessitate a better understanding of the An. gambiae geographical distribution in Ethiopia, accompanied by resistance-informed malaria control interventions targeting the vector.

Graphical Abstract