Identifying Loci Contributing to Natural Variation in Xenobiotic Resistance in Drosophila

Najarro, Michael; Hackett, Jennifer; Smith, Brittny R.; Highfill, Chad; King, Elizabeth G.; Long, Anthony D.; Macdonald, Stuart J.

doi:10.1371/journal.pgen.1005663

Cited by 47 publications

(83 citation statements)

References 74 publications

(120 reference statements)

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“…We show these estimates, along with the haplotype assignments for each individual RIL measurement for all shared QTL in Figure 4. As has been found previously in the DSPR 72,77 and in other mapping panels 78,79 , these effect estimates show evidence for multiple causative variants resulting in an allelic series, not a single causative biallelic SNP that would show haplotype effects in defined "high" and "low" groups. The similar patterns in our effect estimates for learning and memory for a single shared QTL also support the hypothesis that these are pleiotropic loci, rather than separate linked QTL, which would be expected to show contrasting patterns in the two phenotypes.…”

supporting

confidence: 83%

Multiple genetic loci affect place learning and memory performance in Drosophila melanogaster

Williams-Simon

Posey

Mitchell

et al. 2019

Preprint

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Learning and memory are critical functions for all animals, giving individuals the ability to respond to changes in their environment. Within populations, individuals vary, however the mechanisms underlying this variation in performance are largely unknown. Thus, it remains to be determined what genetic factors cause an individual to have high learning ability and what factors determine how well an individual will remember what they have learned. To genetically dissect learning and memory performance, we used the Drosophila synthetic population resource (DSPR), a multiparent mapping resource in the model system Drosophila melanogaster, consisting of a large set of recombinant inbred lines (RILs) that naturally vary in these and other traits. Fruit flies can be trained in a “heat box” to learn to remain on one side of a chamber (place learning) and can remember this (place memory) over short timescales. Using this paradigm, we measured place learning and memory for ~49 000 individual flies from over 700 DSPR RILs. We identified 16 different loci across the genome that significantly affect place learning and/or memory performance, with 5 of these loci affecting both traits. To identify transcriptomic differences associated with performance, we performed RNA‐Seq on pooled samples of seven high performing and seven low performing RILs for both learning and memory and identified hundreds of genes with differences in expression in the two sets. Integrating our transcriptomic results with the mapping results allowed us to identify nine promising candidate genes, advancing our understanding of the genetic basis underlying natural variation in learning and memory performance.

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supporting

confidence: 83%

Multiple genetic loci affect place learning and memory performance in Drosophila melanogaster

Williams-Simon

Posey

Mitchell

et al. 2019

Preprint

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“…pB.Q2 and pB.Q3 mapped in the current study overlap with Q4 and Q5, respectively, as reported in Table 1 from Najarro et al (2015).…”

Section: Resultssupporting

confidence: 52%

Loci Contributing to Boric Acid Toxicity in Two Reference Populations of Drosophila melanogaster

Najarro

Hackett

Macdonald

2017

G3 Genes|Genomes|Genetics

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Populations maintain considerable segregating variation in the response to toxic, xenobiotic compounds. To identify variants associated with resistance to boric acid, a commonly-used household insecticide with a poorly understood mechanism of action, we assayed thousands of individuals from hundreds of strains. Using the Drosophila Synthetic Population Resource (DSPR), a multi-parental population (MPP) of inbred genotypes, we mapped six QTL to short genomic regions containing few protein-coding genes (3–188), allowing us to identify plausible candidate genes underlying resistance to boric acid toxicity. One interval contains multiple genes from the cytochrome P450 family, and we show that ubiquitous RNAi of one of these genes, Cyp9b2, markedly reduces resistance to the toxin. Resistance to boric acid is positively correlated with caffeine resistance. The two phenotypes additionally share a pair of QTL, potentially suggesting a degree of pleiotropy in the genetic control of resistance to these two distinct xenobiotics. Finally, we screened the Drosophila Genetic Reference Panel (DGRP) in an attempt to identify sequence variants within mapped QTL that are associated with boric acid resistance. The approach was largely unsuccessful, with only one QTL showing any associations at QTL-specific 20% False Discovery Rate (FDR) thresholds. Nonetheless, these associations point to a potential candidate gene that can be targeted in future validation efforts. Although the mapping data resulting from the two reference populations do not clearly overlap, our work provides a starting point for further genetic dissection of the processes underlying boric acid toxicity in insects.

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Section: Genomic Scans (Qtl)supporting

confidence: 82%

“…As has been found previously in the DSPR72,77 and in other mapping panels, 78,79 these effect estimates show evidence for multiple causative variants resulting in an allelic series, not a single causative biallelic SNP that would show haplotype effects in defined "high"…”

supporting

confidence: 78%

“…This is a powerful approach to identify genes that are affecting learning and memory via changes in gene expression. Other studies using multiparent populations have used a similar approach of data integration to more effectively identify candidate genes for traits such as resistance to toxins in fruit flies, 77,98 grain yield and flowering time in maize 99 and body weight in mice. 100 While we successfully identified potential candidate genes for many of our QTL, our approach does rely on several important assumptions.…”

Section: Discussionmentioning

confidence: 99%

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Multiple genetic loci affect place learning and memory performance in Drosophila melanogaster

Williams-Simon

Posey

Mitchell

et al. 2019

Genes Brain and Behavior

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Learning and memory are critical functions for all animals, giving individuals the ability to respond to changes in their environment. Within populations, individuals vary, however the mechanisms underlying this variation in performance are largely unknown. Thus, it remains to be determined what genetic factors cause an individual to have high learning ability and what factors determine how well an individual will remember what they have learned. To genetically dissect learning and memory performance, we used the Drosophila synthetic population resource (DSPR), a multiparent mapping resource in the model system Drosophila melanogaster, consisting of a large set of recombinant inbred lines (RILs) that naturally vary in these and othertraits. Fruit flies can be trained in a "heat box" to learn to remain on one side of a chamber (place learning) and can remember this (place memory) over short timescales. Using this paradigm, we measured place learning and memory for~49 000 individual flies from over 700 DSPR RILs. We identified 16 different loci across the genome that significantly affect place learning and/or memory performance, with 5 of these loci affecting both traits. To identify transcriptomic differences associated with performance, we performed RNA-Seq on pooled samples of seven high performing and seven low performing RILs for both learning and memory and identified hundreds of genes with differences in expression in the two sets. Integrating our transcriptomic results with the mapping results allowed us to identify nine promising candidate genes, advancing our understanding of the genetic basis underlying natural variation in learning and memory performance.K E Y W O R D S differential gene expression, Drosophila melanogaster, learning, memory, multiparental population, QTL

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Identifying Loci Contributing to Natural Variation in Xenobiotic Resistance in Drosophila

Cited by 47 publications

References 74 publications

Multiple genetic loci affect place learning and memory performance in Drosophila melanogaster

Multiple genetic loci affect place learning and memory performance in Drosophila melanogaster

Loci Contributing to Boric Acid Toxicity in Two Reference Populations of Drosophila melanogaster

Multiple genetic loci affect place learning and memory performance in Drosophila melanogaster

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