Cytochrome P450s Cyp4p1 and Cyp4p2 associated with the DDT tolerance in the Drosophila melanogaster strain 91-R

Seong, Keon Mook; Coates, Brad S.; Pittendrigh, Barry R.

doi:10.1016/j.pestbp.2019.06.008

Cited by 10 publications

(7 citation statements)

References 57 publications

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“…Four are involved in Dichlorodiphenyltrichloroethane (DDT) resistance. Cyp4p1 (gene class 4) and Cyp4p3 (gene class 4) organized in a gene class on DNA [ 41 ], Cyp6w1 (gene class 4) [ 42 ], and Cyp9c1 (gene class 2) [ 43 ]. Cyp4e1 (gene class 1) has been reported to play a role in permethrin tolerance [ 44 ], and Cyp6d2 (gene class 2) plays a role in the detoxification of toxic compounds [ 45 ].…”

Section: Resultsmentioning

confidence: 99%

Age-Related Changes of Gene Expression Profiles in Drosophila

Bordet

Lodhi

Kossenkov

et al. 2021

Genes

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An individual’s gene expression profile changes throughout their life. This change in gene expression is shaped by differences in physiological needs and functions between the younger and older organism. Despite intensive studies, the aging process is not fully understood, and several genes involved in this process may remain to be identified. Here we report a transcriptomic analysis of Drosophila melanogaster using microarrays. We compared the expression profiles of two-day-old female adult flies with those of 45-day-old flies. We identified 1184 genes with pronounced differences in expression level between young and old age groups. Most genes involved in muscle development/maintenance that display different levels of expression with age were downregulated in older flies. Many of these genes contributed to sarcomere formation and function. Several of these genes were functionally related to direct and indirect flight muscles; some of them were exclusively expressed in these muscles. Conversely, several genes involved in apoptosis processes were upregulated in aging flies. In addition, several genes involved in resistance to toxic chemicals were upregulated in aging flies, which is consistent with a global upregulation of the defense response system in aging flies. Finally, we randomly selected 12 genes among 232 genes with unknown function and generated transgenic flies expressing recombinant proteins fused with GFP protein to determine their subcellular expression. We also found that the knockdown of some of those 12 genes can affect the lifespan of flies.

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Section: Resultsmentioning

confidence: 99%

Age-Related Changes of Gene Expression Profiles in Drosophila

Bordet

Lodhi

Kossenkov

et al. 2021

Genes

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“…First, genome-wide association studies identified DDT-associated multiple genes and signatures of adaptive selection within the genome, where the amino acid changes in Cyp6w1 were associated with DDT resistance 16 . Second, the increased abundance of transcripts for P450s and the likely increased (subsequent) levels of functional translated P450 enzymes have been proposed as a mechanism of resistance to several classes of insecticides 17 , including DDT in Drosophila 18 – 20 . For example, the potential involvement of Cyp4g1 , Cyp6g1 , and Cyp12d1 in DDT resistance in 91-R was demonstrated via independent RNA interface (RNAi)-mediated knockdown of transcripts using the transgenic Gal4/UAS-RNAi expression system, each resulting in increased susceptibility 10 .…”

Section: Introductionmentioning

confidence: 99%

Post-transcriptional modulation of cytochrome P450s, Cyp6g1 and Cyp6g2, by miR-310s cluster is associated with DDT-resistant Drosophila melanogaster strain 91-R

Seong

Coates

Pittendrigh

2020

Sci Rep

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The role of miRNAs in mediating insecticide resistance remains largely unknown, even for the model species Drosophila melanogaster. Building on prior research, this study used microinjection of synthetic miR-310s mimics into DDt-resistant 91-R flies and observed both a significant transcriptional repression of computationally-predicted endogenous target P450 detoxification genes, Cyp6g1 and Cyp6g2, and also a concomitant increase in DDT susceptibility. Additionally, co-transfection of D. melanogaster S2 cells with dual luciferase reporter constructs validated predictions that miR-310s bind to target binding sites in the 3ʹ untranslated regions (3ʹ-UtR) of both Cyp6g1 and Cyp6g2 in vitro. Findings in the current study provide empirical evidence for a link between reduced miRNA expression and an insecticidal resistance phenotype through reduced targeted post-transcriptional suppression of transcripts encoding proteins involved in xenobiotic detoxification. These insights are important for understanding the breadth of adaptive molecular changes that have contributed to the evolution of DDt resistance in D. melanogaster.

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“…Among these, antennal expression of Cyp6a20, which is downregulated in Or47b, Or67d, and fru M mutants, was previously shown to mediate effects of social experience on male-male aggression (Figure 2E) [33]. On the other hand, Cyp4p2, which is involved in hormone metabolism and insecticide detoxification [37][38][39], is only misregulated in Or47b mutants (Figure 2E). In addition to the downregulated genes, we also found some genes encoding ion channels and neurotransmitter receptors that were significantly upregulated (ppk25 and GluRIIa) (Figure 2E).…”

Section: Resultsmentioning

confidence: 97%

“…The copyright holder for this preprint this version posted June 18, 2021. ; https://doi.org/10.1101/2021.06.18.449021 doi: bioRxiv preprint effects of social experience on male-male aggression (Figure 2E) (Wang et al, 2008). On the other hand, Cyp4p2, which is involved in hormone metabolism and insecticide detoxification (Scanlan et al, 2020;Seong et al, 2019Seong et al, , 2018, is only misregulated in Or47b mutants (Figure 2E). In addition to the downregulated genes, we also found some genes encoding ion channels and neurotransmitter receptors that show significant upregulation (ppk25 and GluRIIa) (Figure 2E).…”

Section: Introductionmentioning

confidence: 99%

Social experience and pheromone receptor activity reprogram behavioral switch and neuromodulatory gene expression in sensory neurons

Volkan

Deanhardt

Duan

et al. 2021

Preprint

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Social experience and pheromone signaling in ORNs affect pheromone responses and male courtship behaviors in Drosophila, however, the molecular mechanisms underlying this circuit-level neuromodulation remain less clear. Previous studies identified social experience and pheromone signaling-dependent modulation of chromatin around behavioral switch gene fruitless, which encodes a transcription factor necessary and sufficient for male behaviors. To identify the molecular mechanisms driving social experience-dependent neuromodulation, we performed RNA-seq from antennal samples of mutant fruit flies in pheromone receptors and fruitless, as well as grouped or isolated wild-type males. We found that loss of pheromone detection differentially alters the levels of fruitless exons suggesting changes in splicing patterns. In addition, many Fruitless target neuromodulatory genes, such as neurotransmitter receptors, ion channels, and ion transporters, are differentially regulated by social context and pheromone signaling. Our results suggest that modulation of circuit activity and behaviors in response to social experience and pheromone signaling arise due to changes in transcriptional programs for neuromodulators downstream of behavioral switch gene function.

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Cytochrome P450s Cyp4p1 and Cyp4p2 associated with the DDT tolerance in the Drosophila melanogaster strain 91-R

Cited by 10 publications

References 57 publications

Age-Related Changes of Gene Expression Profiles in Drosophila

Age-Related Changes of Gene Expression Profiles in Drosophila

Post-transcriptional modulation of cytochrome P450s, Cyp6g1 and Cyp6g2, by miR-310s cluster is associated with DDT-resistant Drosophila melanogaster strain 91-R

Social experience and pheromone receptor activity reprogram behavioral switch and neuromodulatory gene expression in sensory neurons

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