Phylogenomic and functional characterization of an evolutionary conserved cytochrome P450-based insecticide detoxification mechanism in bees

Abstract

The regulatory process for assessing the risks of pesticides to bees relies heavily on the use of the honeybee, Apis mellifera , as a model for other bee species. However, the validity of using A. mellifera as a surrogate for other Apis and non- Apis bees in pesticide risk assessment has been questioned. Related to this line of research, recent work on A. mellifera has shown that specific P450 enzymes belonging to the CYP9Q subfamily act as critically important determinants of insecticide sensitivity in this species by efficiently detoxifying certain insecticide chemotypes. However, the extent to which the presence of functional orthologs of these enzymes is conserved across the diversity of bees is unclear. Here we used a phylogenomic approach to identify > 100 putative CYP9Q functional orthologs across 75 bee species encompassing all major bee families. Functional analysis of 26 P450s from 20 representative bee species revealed that P450-mediated detoxification of certain systemic insecticides, including the neonicotinoid thiacloprid and the butenolide flupyradifurone, is conserved across all major bee pollinator families. However, our analyses also reveal that CYP9Q -related genes are not universal to all bee species, with some Megachilidae species lacking such genes. Thus, our results reveal an evolutionary conserved capacity to metabolize certain insecticides across all major bee families while identifying a small number of bee species where this function may have been lost. Furthermore, they illustrate the potential of a toxicogenomic approach to inform pesticide risk assessment for nonmanaged bee species by predicting the capability of bee pollinator species to break down synthetic insecticides.

Mountains as refugia: evidence from bumble bee brain transcriptomes

“…The sublethal effects of these stressors can be detected via changes in gene expression patterns in controlled laboratory studies (Tsvetkov et al, 2021; Costa et al, 2022). Although there is evidence that higher elevations and latitudes may buffer bumble bee populations against all of these anthropogenic stressors (Jackson et al, 2018; Pimsler et al, 2020), we do not have conclusive gene candidates for response to lack of food resources and climate change, in contrast to the strong support that suggests pesticide and pathogen exposure impact detoxification and immune genetic pathways, respectively (Barribeau et al, 2015; Troczka et al, 2019; Haas et al, 2022). There are known challenges associated with analyzing gene expression in wild animals, including high levels of unexplained variation that make functional inferences more difficult (Alvarez et al 2015).…”

“…No reuse allowed without permission. and the Western honey bee (Apis mellifera), though some gene functions have been directly characterized in bumble bees (Haas et al 2022). Changes in gene expression may reflect a negative consequence of the stressor on physiological processes, or the activation of a physiological pathway that enhances resilience to a stressor (Vanette et al, 2015;Grozinger & Zayed, 2020).…”

“…We focused this study on immune and detoxification genes because of their known functions in insect response to pesticide and pathogen exposure (Barribeau et al, 2015; Troczka et al, 2019; Haas et al, 2022). The bumble bee genome contains all of the components of the typical immune pathways in insects (Sadd et al, 2015; Barribeau et al, 2015), though it contains reduced representation of genes amongst the immune pathways, as well as a reduced repertoire of detoxification genes compared to many other insects (Sadd et al, 2015).…”

“…All of these genes have conserved functions related to either detoxification or immune response, though the specific mechanisms and gene expression patterns of each gene are not completely resolved. Most of what we know about the functions of these genes is from research on the fruit fly ( Drosophila ) and the Western honey bee ( Apis mellifera ), though some gene functions have been directly characterized in bumble bees (Haas et al 2022). Changes in gene expression may reflect a negative consequence of the stressor on physiological processes, or the activation of a physiological pathway that enhances resilience to a stressor (Vanette et al, 2015; Grozinger & Zayed, 2020).…”

“…We generated a list of 218 candidate genes from published gene annotations in B. impatiens (Sadd et al, 2015), a Bombus species that is in the same subgenus (Pyrobombus) as B. vosnesenskii and B. melanopygus (Cameron et al, 2007). Our candidate gene list was comprised of 184 immune-related genes (Barribeau et al, 2015) and 24 detoxification genes, which included twelve genes in the Glutathione-S-Transferase (GST) family (Sadd et al, 2015) and 22 genes in the CYP3 p450 (Darragh et al, 2021; Haas et al, 2022).…”