Genomic and Transcriptomic Associations Identify a New Insecticide Resistance Phenotype for the Selective Sweep at the Cyp6g1 Locus of Drosophila melanogaster

Published on Aug 1, 2016in G3: Genes, Genomes, Genetics2.63
· DOI :10.1534/g3.116.031054
Paul Battlay5
Estimated H-index: 5
(University of Melbourne),
Joshua M. Schmidt7
Estimated H-index: 7
(University of Melbourne)
+ 1 AuthorsCharles Robin20
Estimated H-index: 20
(University of Melbourne)
Scans of the Drosophila melanogaster genome have identified organophosphate resistance loci among those with the most pronounced signature of positive selection. In this study, the molecular basis of resistance to the organophosphate insecticide azinphos-methyl was investigated using the Drosophila Genetic Reference Panel, and genome-wide association. Recently released full transcriptome data were used to extend the utility of the Drosophila Genetic Reference Panel resource beyond traditional genome-wide association studies to allow systems genetics analyses of phenotypes. We found that both genomic and transcriptomic associations independently identified Cyp6g1, a gene involved in resistance to DDT and neonicotinoid insecticides, as the top candidate for azinphos-methyl resistance. This was verified by transgenically overexpressing Cyp6g1 using natural regulatory elements from a resistant allele, resulting in a 6.5-fold increase in resistance. We also identified four novel candidate genes associated with azinphos-methyl resistance, all of which are involved in either regulation of fat storage, or nervous system development. In Cyp6g1, we find a demonstrable resistance locus, a verification that transcriptome data can be used to identify variants associated with insecticide resistance, and an overlap between peaks of a genome-wide association study, and a genome-wide selective sweep analysis.
  • References (42)
  • Citations (26)
📖 Papers frequently viewed together
955 Citations
51 Authors (Wen Huang, ..., Trudy F. C. Mackay)
297 Citations
153 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
#1Gillian H. Millburn (University of Cambridge)H-Index: 14
#2Madeline A. Crosby (Harvard University)H-Index: 19
Last. Susan Tweedie (University of Cambridge)H-Index: 24
view all 4 authors...
The use of Drosophila melanogaster as a model for studying human disease is well established, reflected by the steady increase in both the number and proportion of fly papers describing human disease models in recent years. In this article, we highlight recent efforts to improve the availability and accessibility of the disease model information in FlyBase (, the model organism database for Drosophila . FlyBase has recently introduced Human Disease Model Reports, each of which...
29 CitationsSource
#1Jeffrey D. Jensen (EPFL: École Polytechnique Fédérale de Lausanne)H-Index: 39
#2Matthieu Foll (IARC: International Agency for Research on Cancer)H-Index: 27
Last. Louis Bernatchez (Laval University)H-Index: 86
view all 3 authors...
Reference EPFL-ARTICLE-216304doi:10.1111/mec.13493View record in Web of Science Record created on 2016-02-16, modified on 2017-05-12
58 CitationsSource
#1Wen Huang (NCSU: North Carolina State University)H-Index: 24
#2Mary Anna Carbone (NCSU: North Carolina State University)H-Index: 21
Last. Trudy F. C. Mackay (NCSU: North Carolina State University)H-Index: 65
view all 8 authors...
Understanding how DNA sequence variation is translated into variation for complex phenotypes has remained elusive but is essential for predicting adaptive evolution, for selecting agriculturally important animals and crops, and for personalized medicine. Gene expression may provide a link between variation in DNA sequence and organismal phenotypes, and its abundance can be measured efficiently and accurately. Here we quantified genome-wide variation in gene expression in the sequenced inbred lin...
59 CitationsSource
#1Megan E. Garlapow (NCSU: North Carolina State University)H-Index: 2
#2Wen Huang (NCSU: North Carolina State University)H-Index: 24
Last. Trudy F. C. Mackay (NCSU: North Carolina State University)H-Index: 65
view all 5 authors...
Food intake is an essential animal activity, regulated by neural circuits that motivate food localization, evaluate nutritional content and acceptance or rejection responses through the gustatory system, and regulate neuroendocrine feedback loops that maintain energy homeostasis. Excess food consumption in people is associated with obesity and metabolic and cardiovascular disorders. However, little is known about the genetic basis of natural variation in food consumption. To gain insights in evo...
44 CitationsSource
#1Nandita R. Garud (Stanford University)H-Index: 10
#2Philipp W. Messer (Stanford University)H-Index: 28
Last. Dmitri A. Petrov (Stanford University)H-Index: 66
view all 4 authors...
Adaptation from standing genetic variation or recurrent de novo mutation in large populations should commonly generate soft rather than hard selective sweeps. In contrast to a hard selective sweep, in which a single adaptive haplotype rises to high population frequency, in a soft selective sweep multiple adaptive haplotypes sweep through the population simultaneously, producing distinct patterns of genetic variation in the vicinity of the adaptive site. Current statistical methods were expressly...
189 CitationsSource
#1Marko Brankatschk (MPG: Max Planck Society)H-Index: 10
#2Sebastian Dunst (MPG: Max Planck Society)H-Index: 3
Last. Suzanne Eaton (MPG: Max Planck Society)H-Index: 39
view all 4 authors...
How does an animal sense if it is well nourished or not, and then regulate its metabolism appropriately? This process largely relies on the animal's body deciphering signals that that are transmitted between different organs in the form of molecules and hormones. Many animals—ranging from insects to mammals (including humans)—also use their brains to sense and decipher these nutritional signals. A signaling pathway involving the hormone insulin controls how various different animals grow and dev...
27 CitationsSource
#1Wen Huang (NCSU: North Carolina State University)H-Index: 24
#2Andreas Massouras (EPFL: École Polytechnique Fédérale de Lausanne)H-Index: 7
Last. Trudy F. C. Mackay (NCSU: North Carolina State University)H-Index: 65
view all 51 authors...
297 CitationsSource
#1Kin Kuan Hoi (University of Melbourne)H-Index: 5
#2Phillip J. Daborn (University of Melbourne)H-Index: 29
Last. William A. Donald (UNSW: University of New South Wales)H-Index: 20
view all 7 authors...
Insecticide resistance is one of the most prevalent examples of anthropogenic genetic change, yet our understanding of metabolic-based resistance remains limited by the analytical challenges associated with rapidly tracking the in vivo metabolites of insecticides at nonlethal doses. Here, using twin ion mass spectrometry analysis of the extracts of whole Drosophila larvae and excreta, we show that (i) eight metabolites of the neonicotinoid insecticide, imidacloprid, can be detected when formed b...
32 CitationsSource
#1Robert J. Ihry (UW: University of Wisconsin-Madison)H-Index: 7
#2Arash Bashirullah (UW: University of Wisconsin-Madison)H-Index: 9
Steroid hormones trigger a wide variety of biological responses through stage- and tissue-specific activation of target gene expression. The mechanisms that provide specificity to systemically released pulses of steroids, however, remain poorly understood. We previously completed a forward genetic screen for mutations that disrupt the destruction of larval salivary glands during metamorphosis in Drosophila melanogaster, a process triggered by the steroid hormone 20-hydroxyecdysone (ecdysone). He...
15 CitationsSource
126k Citations
Cited By26
#1Jack L Scanlan (University of Melbourne)H-Index: 1
#2Rebecca S. Gledhill-Smith (University of Melbourne)H-Index: 1
Last. Charles Robin (University of Melbourne)H-Index: 20
view all 4 authors...
The capacity to detoxify toxic compounds is essential for adaptation to the ecological niches of many organisms, especially insects. However, detoxification in insects is often viewed through the lens of mammalian detoxification research, even though the organ and enzyme systems involved have diverged for over half a billion years. Phosphorylation is a non-canonical phase II detoxification reaction that, among animals, occurs near exclusively in insects, but the enzymes responsible have never be...
#1Lijuan Zhang (Zhengzhou University)
#1Lijuan Zhang (Zhengzhou University)H-Index: 1
Last. Jinjie Cui (Zhengzhou University)H-Index: 1
view all 10 authors...
The ladybird beetle Propylea japonica is an important natural enemy in agro-ecological systems. Studies on the strong tolerance of P. japonica to high temperatures and insecticides, and its population and phenotype diversity have recently increased. However, abundant genome resources for obtaining insights into stress-resistance mechanisms and genetic intra-species diversity for P. japonica are lacking. Here, we constructed the P. japonica genome maps using Pacific Bioscience (PacBio) and Illumi...
#1Annabelle Haudry (University of Lyon)H-Index: 11
#2Stefan Laurent (MPG: Max Planck Society)H-Index: 10
Last. Martin Kapun (Medical University of Vienna)H-Index: 11
view all 3 authors...
Drosophila melanogaster, a small dipteran of African origin, represents one of the best-studied model organisms. Early work in this system has uniquely shed light on the basic principles of genetics and resulted in a versatile collection of genetic tools that allow to uncover mechanistic links between genotype and phenotype. Moreover, given its worldwide distribution in diverse habitats and its moderate genome-size, Drosophila has proven very powerful for population genetics inference and was on...
#1Annabelle HaudryH-Index: 11
#2Stefan LaurentH-Index: 10
Last. Martin KapunH-Index: 11
view all 3 authors...
Drosophila melanogaster, a small dipteran of African origin, represents one of the best-studied model organisms. Early work in this system has uniquely shed light on the basic principles of genetics and resulted in a versatile collection of genetic tools that allow to uncover mechanistic links between genotype and phenotype. Moreover, given its world-wide distribution in diverse habitats and its moderate genome-size, Drosophila has proven very powerful for population genetics inference and was o...
#1Lili Sun (NEFU: Northeast Forestry University)H-Index: 15
#2Peng Liu (NEFU: Northeast Forestry University)H-Index: 2
Last. Chuanwang Cao (NEFU: Northeast Forestry University)H-Index: 5
view all 8 authors...
The ocular albinism type 1 (OA1), a pigment cell-specific integral membrane glycoprotein, is a member of the G-protein-coupled receptor (GPCR) superfamily that binds to heterotrimeric G proteins in mammalian cells. We aimed to characterize the physiological functions of an insect OA1 in regulation of insecticide stress tolerance. In present study, we investigated the roles of LdOA1 in response to deltamethrin stresses in both Lymantria dispar and Drosophila melanogaster. LdOA1 was expressed at t...
#1Llewellyn Green (University of Melbourne)H-Index: 3
#2Paul Battlay (University of Melbourne)H-Index: 5
Last. Charles Robin (University of Melbourne)H-Index: 20
view all 5 authors...
Insecticide resistance is a paradigm of microevolution, and insecticides are responsible for the strongest cases of recent selection in the genome of Drosophila melanogaster . Here we use a naive population and a novel insecticide class to examine the ab initio genetic architecture of a potential selective response. Genome-wide association studies (GWAS) of chlorantraniliprole susceptibility reveal variation in a gene of major effect, Stretchin Myosin light chain kinase ( Strn-Mlck ), which we v...
3 CitationsSource
#1Alexandre Fournier-Level (University of Melbourne)H-Index: 15
#2Robert T. Good (University of Melbourne)H-Index: 21
Last. Charles Robin (University of Melbourne)H-Index: 20
view all 11 authors...
Imidacloprid, the world’s most used insecticide, has caused considerable controversy due to harmful effects on non-pest species and increasing evidence showing that insecticides have become the primary selective force in many insect species. The genetic response to insecticides is heterogeneous across populations and environments, leading to more complex patterns of genetic variation than previously thought. This motivated the investigation of imidacloprid resistance at different temperatures in...
3 CitationsSource
#1Charles Robin (University of Melbourne)H-Index: 20
#2Paul Battlay (University of Melbourne)H-Index: 5
Last. Alexandre Fournier-Level (University of Melbourne)H-Index: 15
view all 3 authors...
If we are to fully comprehend the evolution of insect diversity at a genomic level we need to understand how natural selection can alter genetically encoded characters within populations. Genetic association panels have the potential to be standard bearers in this endeavour. They enable the mapping of phenotypes to genotypes at unprecedented resolution while simultaneously providing population genomic samples that can be interrogated for the tell-tale signs of selection. Analyses of these panels...
2 CitationsSource
#1S.V. Song (University of Melbourne)H-Index: 1
#2Craig Anderson (Western General Hospital)H-Index: 7
Last. Charles Robin (University of Melbourne)H-Index: 20
view all 7 authors...
Over the last 40 years, many types of population genetic markers have been used to assess the population structure of the pest moth species Helicoverpa armigera. While this species is highly vagile, there is evidence of inter-continental population structure. Here, we examine Z-chromosome molecular markers within and between Chinese and Australian populations. Using 1352 polymorphic sites from 40 Z-linked loci, we compared two Chinese populations of moths separated by 700 km and found virtually ...
1 CitationsSource
#1Paul Battlay (University of Melbourne)H-Index: 5
#2Pontus B. Leblanc (University of Melbourne)H-Index: 2
Last. Charles Robin (University of Melbourne)H-Index: 20
view all 7 authors...
Patterns of nucleotide polymorphism within populations of Drosophila melanogaster suggest that insecticides have been the selective agents driving the strongest recent bouts of positive selection. However, there is a need to explicitly link selective sweeps to the particular insecticide phenotypes that could plausibly account for the drastic selective responses that are observed in these non-target insects. Here, we screen the Drosophila Genetic Reference Panel with two common insecticides; mala...
5 CitationsSource