Genetic Diversity of Cytochrome P450 Genes in Apis mellifera Subspecies

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The study analyzed genetic diversity across the cytochrome P450 (CYP) detoxification system in 1,467 western honey bees spanning 18 Apis mellifera subspecies from 25 countries, identifying 5,756 SNPs across 46 CYP genes. Using population and selection analyses including imputed McDonald–Kreitman tests, the authors found that 56% of non-synonymous CYP substitutions were consistent with positive selection, with adaptive variation concentrated in the CYP3 clan, especially CYP9 and CYP6AS. They also reported extensive haplotype diversity (1,302 haplotypes) with 84% in CYP3, supported by nucleotide diversity, Tajima’s D, and FST differentiation. The paper frames this as a first comprehensive CYPome analysis and does not provide direct functional validation of detoxification phenotypes. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

The western honey bee ( Apis mellifera ) is an essential pollinator facing unprecedented threats from pesticide exposure. While pesticide resistance evolution is well documented in agricultural pests, our understanding of genetic variation in honey bee detoxification systems remains limited. This represents a missed opportunity, as harnessing naturally occurring detoxification diversity could provide new avenues for pollinator protection. Cytochrome P450 monooxygenases (CYPs), which are central to xenobiotic metabolism, offer a promising starting point. Here, we present the first comprehensive analysis of CYP genetic diversity in A. mellifera . We analysed the CYPome of 1,467 individuals representing 18 A. mellifera subspecies from 25 countries and identified 5,756 single-nucleotide polymorphisms (SNPs) in 46 CYP genes. Imputed McDonald-Kreitman testing revealed that 56% of non-synonymous CYP substitutions were driven by positive selection. Of the 1,302 haplotypes identified, 84% resided in CYP3, concentrated in the CYP9 and CYP6AS subfamilies implicated in xenobiotic detoxification. Population-level analysis of nucleotide diversity, Tajima’s D selection signatures, F ST -based differentiation, and McDonald-Kreitman testing pointed to CYP3 clan genes as the primary locus of adaptive variation. This work provides the first step toward building a comprehensive pharmacogenomic resource for honey bees, enabling the prediction of population-specific pesticide vulnerabilities and leveraging naturally occurring detoxification variants to enhance pollinator resilience – a critical step toward sustainable pollinator management.
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Abstract The western honey bee (Apis mellifera) is an essential pollinator facing unprecedented threats from pesticide exposure. While pesticide resistance evolution is well documented in agricultural pests, our understanding of genetic variation in honey bee detoxification systems remains limited. This represents a missed opportunity, as harnessing naturally occurring detoxification diversity could provide new avenues for pollinator protection. Cytochrome P450 monooxygenases (CYPs), which are central to xenobiotic metabolism, offer a promising starting point. Here, we present the first comprehensive analysis of CYP genetic diversity in A. mellifera. We analysed the CYPome of 1,467 individuals representing 18 A. mellifera subspecies from 25 countries and identified 5,756 single-nucleotide polymorphisms (SNPs) in 46 CYP genes. Imputed McDonald-Kreitman testing revealed that 56% of non-synonymous CYP substitutions were driven by positive selection. Of the 1,302 haplotypes identified, 84% resided in CYP3, concentrated in the CYP9 and CYP6AS subfamilies implicated in xenobiotic detoxification. Population-level analysis of nucleotide diversity, Tajima’s D selection signatures, FST-based differentiation, and McDonald-Kreitman testing pointed to CYP3 clan genes as the primary locus of adaptive variation. This work provides the first step toward building a comprehensive pharmacogenomic resource for honey bees, enabling the prediction of population-specific pesticide vulnerabilities and leveraging naturally occurring detoxification variants to enhance pollinator resilience – a critical step toward sustainable pollinator management. Competing Interest Statement The authors have declared no competing interest.

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