Genomic and transcriptomic analyses in Drosophila suggest that the ecdysteroid kinase-like (EcKL) gene family encodes the ‘detoxification-by-phosphorylation’ enzymes of insects

Scanlan, Jack L.; Gledhill-Smith, Rebecca S.; Battlay, Paul; Robin, Charles

doi:10.1016/j.ibmb.2020.103429

Cited by 26 publications

(57 citation statements)

References 177 publications

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“…Cytochrome P450 genes often play a critical role in phase 1 of the metabolism and sequestration of plant specialised metabolites through the oxidation, reduction, or hydrolysis of compounds (Birnbaum and Abbot, 2020). One of the two genes upregulated in AC+ individuals, Cyp4c3, has been linked to xenobiotic resistance in Drosophila (Scanlan et al, 2020) and many genes in the insect CYP4 family play a role in detoxification in insects (Scott, 1999;Vogel et al, 2014). Despite this, no other genes or pathways directly linked to detoxification or sequestration were upregulated in AC+.…”

Section: Discussionmentioning

confidence: 99%

Consequences of pharmacophagous uptake from plants and conspecifics in a sawfly elucidated using chemical and molecular techniques

Paul

Dennis

et al. 2021

Preprint

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Pharmacophagy involves the sequestration of specialised plant metabolites for non-nutritive purposes and commonly occurs in insects. Here we investigate pharmacophagy in the turnip sawfly, Athalia rosae, where adults not only collect specialised metabolites (clerodanoids) from a plant (Ajuga reptans), but also from the exterior of conspecifics via fighting. Using behavioural assays, chemical analytics, and RNAseq we show that when individuals nibble on conspecifics that have already acquired clerodanoids from A. reptans leaves, this nibbling results in the transfer of compounds between individuals. Furthermore, unlike other pharmacophagous insects, the acquisition of clerodanoids by A. rosae from the leaves of A. reptans does not induce the upregulation of known detoxification or sequestration genes and pathways. In contrast, pharmacophagous nibbling on conspecifics results in the upregulation of metabolic pathways associated with elevated metabolic rates and increased energy consumption. It therefore seems that individuals attack conspecifics to acquire clerodanoids despite the apparent metabolic costs of this form of pharmacophagy compared to clerodanoid uptake from a plant. Changes in the metabolic phenotype of A.rosae individuals consequently has profound consequences for social interactions with possible ramifications for their social niche.

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Section: Discussionmentioning

confidence: 99%

Consequences of pharmacophagous uptake from plants and conspecifics in a sawfly elucidated using chemical and molecular techniques

Paul

Dennis

et al. 2021

Preprint

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“…Additionally, each of these three CYPs has a high level of genomic instability, with frequent gene gain and loss events across Drosophila species 21 . These findings, together with the enrichment of Cyp4p1, Cyp6a8 , and Cyp6d5 in tissues associated with detoxification such as the midgut, Malpighian tubules and fat body, suggests they function in xenobiotic detoxification rather than the synthesis or degradation of products as part of developmental or physiological processes 18 . This would be consistent with a role for these CYPs in the degradation of odorants such as geranyl acetate.…”

Section: Discussionmentioning

confidence: 98%

Evaluation of a high-throughput deorphanization strategy to identify cytochrome p450s important for odor degradation inDrosophila

Baldwin

Mohapatra

Nagalla

et al. 2021

Preprint

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Members of the cytochrome p450 (CYP) enzyme family are abundantly expressed in insect olfactory tissues, where they are thought to act as Odorant Degrading Enzymes (ODEs). However, their contribution to olfactory signaling in vivo is poorly understood. This is due in part to the challenge of identifying which of the dozens of antennal-expressed CYPs might inactivate a given odorant. Here, we tested a high-throughput deorphanization strategy in Drosophila to identify CYPs that are transcriptionally induced by exposure to a plant volatile. We discovered three CYPs selectively upregulated by the odorant using transcriptional profiling. Although these CYPs are shown to be broadly expressed in the antenna in non-neuronal cells, electrophysiological recordings from CYP mutants did not reveal any changes in olfactory neuron responses to the odorant. Neurons were desensitized by pre-exposing flies to the odorant, but this effect was similar in CYP mutants. Together, our data suggest that this transcriptomic approach may not be useful for identifying CYPs that contribute to olfactory signaling. We go on to show that some CYPs have highly restricted expression patterns in the antenna, and suggest that such CYPs may be useful candidates for further studies on olfactory CYP function.

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“…A critical hurdle in the identification of CYPs with olfactory roles is that the substrates of most CYPs in Drosophila , the most genetically amenable organism, are unknown 9 , 18 . Further, many insect CYPs with roles in xenobiotic metabolism act on multiple substrates 19 , and thus the identification of one substrate does not preclude another.…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, it is not yet possible to predict substrates from CYP sequences alone because they have highly divergent protein sequences, despite their conserved three dimensional structure 20 . It is estimated that one-third of the Drosophila CYP family is involved in metabolizing environmental xenobiotics based on their evolutionary instability, enrichment in tissues commonly associated with detoxification, and ability to be induced by xenobiotics 18 , 21 . Of these, ~ 90% are expressed in the Drosophila antenna 11 , 12 .…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of CYPs induced in the Drosophila antenna by exposure to a plant odorant

Baldwin

Mohapatra

Nagalla

et al. 2021

Sci Rep

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Members of the cytochrome p450 (CYP) enzyme family are abundantly expressed in insect olfactory tissues, where they are thought to act as Odorant Degrading Enzymes (ODEs). However, their contribution to olfactory signaling in vivo is poorly understood. This is due in part to the challenge of identifying which of the dozens of antennal-expressed CYPs might inactivate a given odorant. Here, we tested a high-throughput deorphanization strategy in Drosophila to identify CYPs that are transcriptionally induced by exposure to odorants. We discovered three CYPs selectively upregulated by geranyl acetate using transcriptional profiling. Although these CYPs are broadly expressed in the antenna in non-neuronal cells, electrophysiological recordings from CYP mutants did not reveal any changes in olfactory neuron responses to this odorant. Neurons were desensitized by pre-exposing flies to the odorant, but this effect was similar in CYP mutants. Together, our data suggest that the induction of a CYP gene by an odorant does not necessarily indicate a role for that CYP in neuronal responses to that odorant. We go on to show that some CYPs have highly restricted expression patterns in the antenna, and suggest that such CYPs may be useful candidates for further studies on olfactory CYP function.

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Genomic and transcriptomic analyses in Drosophila suggest that the ecdysteroid kinase-like (EcKL) gene family encodes the ‘detoxification-by-phosphorylation’ enzymes of insects

Cited by 26 publications

References 177 publications

Consequences of pharmacophagous uptake from plants and conspecifics in a sawfly elucidated using chemical and molecular techniques

Consequences of pharmacophagous uptake from plants and conspecifics in a sawfly elucidated using chemical and molecular techniques

Evaluation of a high-throughput deorphanization strategy to identify cytochrome p450s important for odor degradation inDrosophila

Identification and characterization of CYPs induced in the Drosophila antenna by exposure to a plant odorant

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