Loci Contributing to Boric Acid Toxicity in Two Reference Populations of<i>Drosophila melanogaster</i>

Najarro, Michael; Hackett, Jennifer; Macdonald, Stuart J.

doi:10.1534/g3.117.041418

Cited by 29 publications

(19 citation statements)

References 72 publications

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“…Assuming that each 452 QTL contributes to phenotypic variation in an additive manner, the QTL explained a substantial 453 amount of variation in adult copper resistance ( Figure 5A). Panel-specific 457 genetic architecture of trait variation is consistent with several other studies that have mapped 458 traits in both panels of the DSPR (Marriage et al 2014;Najarro et al 2017;Everman et al 2019). 459…”

Section: Copper-specific Developmental Responsesupporting

confidence: 78%

Characterizing the genetic basis of copper toxicity inDrosophilareveals a complex pattern of allelic, regulatory, and behavioral variation

Everman

Cloud-Richardson

Macdonald

2020

Preprint

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1A range of heavy metals are required for normal cell function and homeostasis. Equally, 2 the anthropogenic release of heavy metals into soil and water sources presents a pervasive 3 health threat. Copper is one such metal; it functions as a critical enzymatic cofactor, but at high 4 concentrations is toxic, and can lead to the production of reactive oxygen species. Using a 5 combination of quantitative trait locus (QTL) mapping and RNA sequencing in the Drosophila 6Synthetic Population Resource (DSPR), we demonstrate that resistance to the toxic effects of 7 ingested copper in D. melanogaster is genetically complex, and influenced by allelic and 8 expression variation at multiple loci. Additionally, we find that copper resistance is impacted by 9 variation in behavioral avoidance of copper and may be subject to life-stage specific regulation. 10Multiple genes with known copper-specific functions, as well as genes that are involved in the 11 regulation of other heavy metals were identified as potential candidates to contribute to 12 variation in adult copper resistance. We demonstrate that nine of 16 candidates tested by RNAi 13 knockdown influence adult copper resistance, a number of which may have pleiotropic effects 14 since they have previously been shown to impact the response to other metals. Our work 15 provides new understanding of the genetic complexity of copper resistance, highlighting the 16 diverse mechanisms through which copper pollution can negatively impact organisms. 17Additionally, we further support the similarities between copper metabolism and that of other 18 essential and nonessential heavy metals. 19 20 Rearing and assay conditions 126Strains from the DSPR were maintained, reared, and tested in the same incubator under 127 a 12:12hr light:dark photoperiod at 25°C and 50% humidity. To obtain female flies for the adult 128 copper response assay, RNA sequencing, and RNAi validation, adults were transferred to 129 cornmeal-molasses-yeast food, allowed to oviposit for two days, then discarded. Experimental 130 female, presumably mated, flies from the following generation were sorted over CO2 and were 131 placed into vials with new cornmeal-molasses-yeast media for 24 hours prior to the start of each 132 assay before they were transferred to copper-supplemented food. All adult assays were 133 performed on 3-5 day old individuals. 134

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Section: Copper-specific Developmental Responsesupporting

confidence: 78%

Characterizing the genetic basis of copper toxicity inDrosophilareveals a complex pattern of allelic, regulatory, and behavioral variation

Everman

Cloud-Richardson

Macdonald

2020

Preprint

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“…(A simulation that excluded the very large physical interval implicated by QG7 revealed a similar lack of enrichment of GWAS associations within QTL.) We have previously seen a similar lack of overlap between mapping results in the DGRP and DSPR for three toxicity and stress tolerance traits [50][51][52]. This lack of replication is likely due to a combination of power deficits [49], differences in environmental and assay conditions (see above), and the fact that many variants do not segregate in both the DGRP and DSPR [34].…”

Section: Overlap With Loci Previously Implicated In the Genetic Contrmentioning

confidence: 72%

Dissecting the Genetic Basis of Variation in Drosophila Sleep Using a Multiparental QTL Mapping Resource

Smith

Macdonald

2020

Genes

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There is considerable variation in sleep duration, timing and quality in human populations, and sleep dysregulation has been implicated as a risk factor for a range of health problems. Human sleep traits are known to be regulated by genetic factors, but also by an array of environmental and social factors. These uncontrolled, non-genetic effects complicate powerful identification of the loci contributing to sleep directly in humans. The model system, Drosophila melanogaster, exhibits a behavior that shows the hallmarks of mammalian sleep, and here we use a multitiered approach, encompassing high-resolution QTL mapping, expression QTL data, and functional validation with RNAi to investigate the genetic basis of sleep under highly controlled environmental conditions. We measured a battery of sleep phenotypes in >750 genotypes derived from a multiparental mapping panel and identified several, modest-effect QTL contributing to natural variation for sleep. Merging sleep QTL data with a large head transcriptome eQTL mapping dataset from the same population allowed us to refine the list of plausible candidate causative sleep loci. This set includes genes with previously characterized effects on sleep and circadian rhythms, in addition to novel candidates. Finally, we employed adult, nervous system-specific RNAi on the Dopa decarboxylase, dyschronic, and timeless genes, finding significant effects on sleep phenotypes for all three. The genes we resolve are strong candidates to harbor causative, regulatory variation contributing to sleep.

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“…By searching the GenBank database, the four up-regulated unigene comp30167, 38558, 40700 and 44013 were annotated similar with CYP9b2 in Culex quinquefasciatus , P450s gene in Anopheles darlingi genome, CYP49a1 in Aedes aegypti and CYP12b1 in Culex quinquefasciatus , respectively. While it had been reported that CYP9b2 in Drosophila melanogaster was related to toxin resistance 29 , CYP49a1 expressed in Bombyx morito was involved in phoxim metabolism 30 and CYP12b1 as a mitochondrial P450 may be related to biological process in Drosophila acanthoptera 31 . So far, no any imidaclodprid detoxification related annotation could be found for the four up-regulated P450 unigenes.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis and identification of P450 genes relevant to imidacloprid detoxification in Bradysia odoriphaga

Chen

Wang

Liu

et al. 2018

Sci Rep

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Pesticide tolerance poses many challenges for pest control, particularly for destructive pests such as Bradysia odoriphaga. Imidacloprid has been used to control B. odoriphaga since 2013, however, imidacloprid resistance in B. odoriphaga has developed in recent years. Identifying actual and potential genes involved in detoxification metabolism of imidacloprid could offer solutions for controlling this insect. In this study, RNA-seq was used to explore differentially expressed genes in B. odoriphaga that respond to imidacloprid treatment. Differential expression data between imidacloprid treatment and the control revealed 281 transcripts (176 with annotations) showing upregulation and 394 transcripts (235 with annotations) showing downregulation. Among them, differential expression levels of seven P450 unigenes were associated with imidacloprid detoxification mechanism, with 4 unigenes that were upregulated and 3 unigenes that were downregulated. The qRT-PCR results of the seven differential expression P450 unigenes after imidacloprid treatment were consistent with RNA-Seq data. Furthermore, oral delivery mediated RNA interference of these four upregulated P450 unigenes followed by an insecticide bioassay significantly increased the mortality of imidacloprid-treated B. odoriphaga. This result indicated that the four upregulated P450s are involved in detoxification of imidacloprid. This study provides a genetic basis for further exploring P450 genes for imidacloprid detoxification in B. odoriphaga.

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Loci Contributing to Boric Acid Toxicity in Two Reference Populations ofDrosophila melanogaster

Cited by 29 publications

References 72 publications

Characterizing the genetic basis of copper toxicity inDrosophilareveals a complex pattern of allelic, regulatory, and behavioral variation

Characterizing the genetic basis of copper toxicity inDrosophilareveals a complex pattern of allelic, regulatory, and behavioral variation

Dissecting the Genetic Basis of Variation in Drosophila Sleep Using a Multiparental QTL Mapping Resource

Transcriptome analysis and identification of P450 genes relevant to imidacloprid detoxification in Bradysia odoriphaga

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