RESUMO
It is a common observation that distinct lineages adapt to similar environments through similar "parallel" changes in phenotype. Less clear is whether parallel phenotypic change evolves through genetic variation in the same or distinct genes. This question of redundancy-the number of genetic answers to the same evolutionary problem-is an important yet poorly understood feature of adaptive traits, and is a major hurdle in our transition from understanding evolutionary responses to predicting them. In this issue of Molecular Ecology, Szukala et al. (2023) examine the redundancy of local adaptation in montane and alpine ecotypes that has occurred in the flowering plant Heliosperma pusillum. By comparing gene expression in each of four montane or alpine-adapted H. pusillum population pairs, the authors observe distinct genetic responses underlying each case of parallel local adaptation.
Assuntos
Aclimatação , Adaptação Fisiológica , Adaptação Fisiológica/genética , Ecologia , Evolução Biológica , FenótipoRESUMO
The nematode Caenorhabditis elegans is among the most widely studied organisms, but relatively little is known about its natural ecology. Genetic diversity is low across much of the globe but high in the Hawaiian Islands and across the Pacific Rim. To characterize the niche and genetic diversity of C. elegans on the Hawaiian Islands and to explore how genetic diversity might be influenced by local adaptation, we repeatedly sampled nematodes over a three-year period, measured various environmental parameters at each sampling site, and whole-genome sequenced the C. elegans isolates that we identified. We found that the typical Hawaiian C. elegans niche comprises moderately moist native forests at high elevations (500-1,500 m) where ambient air temperatures are cool (15-20°C). Compared to other Caenorhabditis species found on the Hawaiian Islands (e.g., Caenorhabditis briggsae and Caenorhabditis tropicalis), we found that C. elegans were enriched in native habitats. We measured levels of genetic diversity and differentiation among Hawaiian C. elegans and found evidence of seven genetically distinct groups distributed across the islands. Then, we scanned these genomes for signatures of local adaptation and identified 18 distinct regions that overlap with hyper-divergent regions, which may be maintained by balancing selection and are enriched for genes related to environmental sensing, xenobiotic detoxification, and pathogen resistance. These results provide strong evidence of local adaptation among Hawaiian C. elegans and contribute to our understanding of the forces that shape genetic diversity on the most remote volcanic archipelago in the world.
Assuntos
Caenorhabditis elegans , Caenorhabditis , Animais , Caenorhabditis/genética , Variação Genética/genética , Havaí , IlhasRESUMO
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 naïve 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 validate with linkage mapping and transgenic manipulation of gene expression. We propose that allelic variation in Strn-Mlck alters sensitivity to the calcium depletion attributable to chlorantraniliprole's mode of action. GWAS also reveal a network of genes involved in neuromuscular biology. In contrast, phenotype to transcriptome associations identify differences in constitutive levels of multiple transcripts regulated by cnc, the homolog of mammalian Nrf2. This suggests that genetic variation acts in trans to regulate multiple metabolic enzymes in this pathway. The most outstanding association is with the transcription level of Cyp12d1 which is also affected in cis by copy number variation. Transgenic overexpression of Cyp12d1 reduces susceptibility to both chlorantraniliprole and the closely related insecticide cyantraniliprole. This systems genetics study reveals multiple allelic variants segregating at intermediate frequency in a population that is completely naïve to this new insecticide chemistry and it foreshadows a selective response among natural populations to these chemicals.
Assuntos
Variações do Número de Cópias de DNA/genética , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/genética , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Transativadores/genética , Alelos , Animais , Animais Geneticamente Modificados , Mapeamento Cromossômico/métodos , Variações do Número de Cópias de DNA/efeitos dos fármacos , Proteínas de Drosophila/genética , Estudo de Associação Genômica Ampla/métodos , Quinase de Cadeia Leve de Miosina/genética , Fenótipo , Pirazóis/farmacologia , Sobrevivência , Transcriptoma/efeitos dos fármacos , Transcriptoma/genética , ortoaminobenzoatos/farmacologiaRESUMO
Biological invasions are accelerating, and invasive species can have large economic impacts as well as severe consequences for biodiversity. During invasions, species can interact, potentially resulting in hybridization. Here, we examined two Cakile species, C. edentula and C. maritima (Brassicaceae), that co-occur and may hybridize during range expansion in separate regions of the globe. Cakile edentula invaded each location first, while C. maritima established later, apparently replacing the former. We assessed the evidence for hybridization in western North America and Australia, where both species have been introduced, and identified source populations with 4561 SNPs using Genotype-by-Sequencing. Our results indicate that C. edentula in Australia originated from one region of eastern North America while in western North America it is probably from multiple sources. Cakile maritima in Australia is derived from at least two different parts of Europe while the introduction in western North America is from one. Although morphological evidence of hybridization is generally limited to mixed species populations in Australia and virtually absent elsewhere, our genetic analysis revealed relatively high levels of hybridization in Australia (58% hybrids using Admixture) and supported the presence of hybrids in western North America (16% hybrids using Admixture) and New Zealand. Hybrids might be commonly overlooked in invaders, as identification based solely on morphological traits may represent only the tip of the iceberg. Our study reveals a repeated pattern of invasion, hybridization and apparent replacement of one species by another, which offers an opportunity to investigate the role of hybridization and introgression during invasion.
Assuntos
Brassicaceae/genética , Hibridização Genética , Espécies Introduzidas , Austrália , Europa (Continente) , Nova Zelândia , América do NorteRESUMO
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 by susceptible larval genotypes and (ii) the specific overtranscription of a single gene product, Cyp6g1, associated with the metabolic resistance to neonicotinoids, results in a significant increase in the formation of three imidacloprid metabolites that are formed in C-H bond activation reactions; that is, Cyp6g1 is directly linked to the enhanced metabolism of imidacloprid in vivo. These results establish a rapid and sensitive method for dissecting the metabolic machinery of insects by directly linking single gene products to insecticide metabolism.
Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Imidazóis/metabolismo , Inseticidas/metabolismo , Espectrometria de Massas/métodos , Nitrocompostos/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Drosophila melanogaster , NeonicotinoidesRESUMO
Observations of genetically repeated evolution (repeatability) in complex organisms are incongruent with the Fisher-Orr model, which implies that repeated use of the same gene should be rare when mutations are pleiotropic (i.e. affect multiple traits). When spatially divergent selection occurs in the presence of migration, mutations of large effect are more strongly favored, and hence, repeatability is more likely, but it is unclear whether this observation is limited by pleiotropy. Here, we explore this question using individual-based simulations of a two-patch model incorporating multiple quantitative traits governed by mutations with pleiotropic effects. We explore the relationship between fitness trade-offs and repeatability by varying the alignment between mutation effect and spatial variation in trait optima. While repeatability decreases with increasing trait dimensionality, trade-offs in mutation effects on traits do not strongly limit the contribution of a locus of large effect to repeated adaptation, particularly under increased migration. These results suggest that repeatability will be more pronounced for local rather than global adaptation. Whereas pleiotropy limits repeatability in a single-population model, when there is local adaptation with gene flow, repeatability can occur if some loci are able to produce alleles of large effect, even when there are pleiotropic trade-offs.
Assuntos
Pleiotropia Genética , Modelos Genéticos , Mutação , Seleção Genética , Adaptação Fisiológica/genética , Animais , Evolução Molecular , Migração Animal , Aptidão GenéticaRESUMO
Human activities are accelerating rates of biological invasions and climate-driven range expansions globally, yet we understand little of how genomic processes facilitate the invasion process. Although most of the literature has focused on underlying phenotypic correlates of invasiveness, advances in genomic technologies are showing a strong link between genomic variation and invasion success. Here, we consider the ability of genomic tools and technologies to (i) inform mechanistic understanding of biological invasions and (ii) solve real-world issues in predicting and managing biological invasions. For both, we examine the current state of the field and discuss how genomics can be leveraged in the future. In addition, we make recommendations pertinent to broader research issues, such as data sovereignty, metadata standards, collaboration, and science communication best practices that will require concerted efforts from the global invasion genomics community.
Assuntos
Genômica , Espécies Introduzidas , Humanos , ClimaRESUMO
White clover (Trifolium repens L.; Fabaceae) is an important forage and cover crop in agricultural pastures around the world and is increasingly used in evolutionary ecology and genetics to understand the genetic basis of adaptation. Historically, improvements in white clover breeding practices and assessments of genetic variation in nature have been hampered by a lack of high-quality genomic resources for this species, owing in part to its high heterozygosity and allotetraploid hybrid origin. Here, we use PacBio HiFi and chromosome conformation capture (Omni-C) technologies to generate a chromosome-level, haplotype-resolved genome assembly for white clover totaling 998 Mbp (scaffold N50 = 59.3 Mbp) and 1 Gbp (scaffold N50 = 58.6 Mbp) for haplotypes 1 and 2, respectively, with each haplotype arranged into 16 chromosomes (8 per subgenome). We additionally provide a functionally annotated haploid mapping assembly (968 Mbp, scaffold N50 = 59.9 Mbp), which drastically improves on the existing reference assembly in both contiguity and assembly accuracy. We annotated 78,174 protein-coding genes, resulting in protein BUSCO completeness scores of 99.6% and 99.3% against the embryophyta_odb10 and fabales_odb10 lineage datasets, respectively.
Assuntos
Trifolium , Trifolium/genética , Haplótipos , Melhoramento Vegetal , Medicago/genética , CromossomosRESUMO
Adaptation is the central feature and leading explanation for the evolutionary diversification of life. Adaptation is also notoriously difficult to study in nature, owing to its complexity and logistically prohibitive timescale. Here, we leverage extensive contemporary and historical collections of Ambrosia artemisiifolia-an aggressively invasive weed and primary cause of pollen-induced hayfever-to track the phenotypic and genetic causes of recent local adaptation across its native and invasive ranges in North America and Europe, respectively. Large haploblocks-indicative of chromosomal inversions-contain a disproportionate share (26%) of genomic regions conferring parallel adaptation to local climates between ranges, are associated with rapidly adapting traits, and exhibit dramatic frequency shifts over space and time. These results highlight the importance of large-effect standing variants in rapid adaptation, which have been critical to A. artemisiifolia's global spread across vast climatic gradients.
Assuntos
Ambrosia , Plantas Daninhas , Ambrosia/genética , Plantas Daninhas/genética , Aclimatação , Adaptação Fisiológica/genética , Evolução BiológicaRESUMO
A unique aspect of metabolic detoxification in insects compared to other animals is the presence of xenobiotic phosphorylation, about which little is currently understood. Our previous work raised the hypothesis that members of the taxonomically restricted ecdysteroid kinase-like (EcKL) gene family encode the enzymes responsible for xenobiotic phosphorylation in the model insect Drosophila melanogaster (Diptera: Ephydroidea)-however, candidate detoxification genes identified in the EcKL family have yet to be functionally validated. Here, we test the hypothesis that EcKL genes in the rapidly evolving Dro5 clade are involved in the detoxification of plant and fungal toxins in D. melanogaster. The mining and reanalysis of existing data indicated multiple Dro5 genes are transcriptionally induced by the plant alkaloid caffeine and that adult caffeine susceptibility is associated with a novel naturally occurring indel in CG31370 (Dro5-8) in the Drosophila Genetic Reference Panel (DGRP). CRISPR-Cas9 mutagenesis of five Dro5 EcKLs substantially decreased developmental tolerance of caffeine, while individual overexpression of two of these genes-CG31300 (Dro5-1) and CG13659 (Dro5-7)-in detoxification-related tissues increased developmental tolerance. In addition, we found Dro5 loss-of-function animals also have decreased developmental tolerance of the fungal secondary metabolite kojic acid. Taken together, this work provides the first compelling functional evidence that EcKLs encode detoxification enzymes and suggests that EcKLs in the Dro5 clade are involved in the metabolism of multiple ecologically relevant toxins in D. melanogaster. We also propose a biochemical hypothesis for EcKL involvement in caffeine detoxification and highlight the many unknown aspects of caffeine metabolism in D. melanogaster and other insects.
RESUMO
BACKGROUND: The adaptive significance of polyploidy has been extensively debated, and chromosome-level genome assemblies of polyploids can provide insight into this. The Australian grass Bothriochloa decipiens belongs to the BCD clade, a group with a complex history of hybridization and polyploid. This is the first genome assembly and annotation of a species that belongs to this fascinating yet complex group. FINDINGS: Using Illumina short reads, 10X Genomics linked reads, and Hi-C sequencing data, we assembled a highly contiguous genome of B. decipiens, with a total length of 1,218.22 Mb and scaffold N50 of 42.637 Mb. Comparative analysis revealed that the species experienced a relatively recent whole-genome duplication. We clustered the 20 major scaffolds, representing the 20 chromosomes, into the 2 subgenomes of the parental species using unique repeat signatures. We found evidence of biased fractionation and differences in the activity of transposable elements between the subgenomes prior to hybridization. Duplicates were enriched for genes involved in transcription and response to external stimuli, supporting a biased retention of duplicated genes following whole-genome duplication. CONCLUSIONS: Our results support the hypotheses of a biased retention of duplicated genes following polyploidy and point to differences in repeat activity associated with subgenome dominance. B. decipiens is a widespread species with the ability to establish across many soil types, making it a prime candidate for climate change- resilient ecological restoration of Australian grasslands. This reference genome is a valuable resource for future population genomic research on Australian grasses.
Assuntos
Duplicação Gênica , Poaceae , Austrália , Genoma de Planta , Poaceae/genética , PoliploidiaRESUMO
Biological invasions offer a unique opportunity to investigate evolution over contemporary timescales. Rapid adaptation to local climates during range expansion can be a major determinant of invasion success, yet fundamental questions remain about its genetic basis. This study sought to investigate the genetic basis of climate adaptation in invasive common ragweed (Ambrosia artemisiifolia). Flowering time adaptation is key to this annual species' invasion success, so much so that it has evolved repeated latitudinal clines in size and phenology across its native and introduced ranges despite high gene flow among populations. Here, we produced a high-density linkage map (4493 SNPs) and paired this with phenotypic data from an F2 mapping population (n = 336) to identify one major and two minor quantitative trait loci (QTL) underlying flowering time and height differentiation in this species. Within each QTL interval, several candidate flowering time genes were also identified. Notably, the major flowering time QTL detected in this study was found to overlap with a previously identified haploblock (putative inversion). Multiple genetic maps of this region identified evidence of suppressed recombination in specific genotypes, consistent with inversions. These discoveries support the expectation that a concentrated genetic architecture with fewer, larger, and more tightly linked alleles should underlie rapid local adaptation during invasion, particularly when divergently adapting populations experience high levels of gene flow.
RESUMO
Invasive species are a key driver of the global biodiversity crisis, but the drivers of invasiveness, including the role of pathogens, remain debated. We investigated the genomic basis of invasiveness in Ambrosia artemisiifolia (common ragweed), introduced to Europe in the late 19th century, by resequencing 655 ragweed genomes, including 308 herbarium specimens collected up to 190 years ago. In invasive European populations, we found selection signatures in defense genes and lower prevalence of disease-inducing plant pathogens. Together with temporal changes in population structure associated with introgression from closely related Ambrosia species, escape from specific microbial enemies likely favored the plant's remarkable success as an invasive species.
Assuntos
Ambrosia , Espécies Introduzidas , Ambrosia/genética , Europa (Continente) , Genômica , Análise de Sequência de DNARESUMO
Phosphorylation is a phase II detoxification reaction that, among animals, occurs near exclusively in insects, but the enzymes responsible have never been cloned or otherwise identified. We propose the hypothesis that members of the arthropod-specific ecdysteroid kinase-like (EcKL) gene family encode detoxicative kinases. To test this hypothesis, we annotated the EcKL gene family in 12 species of Drosophila and explored their evolution within the genus. Many ancestral EcKL clades are evolutionarily unstable and have experienced repeated gene gain and loss events, while others are conserved as single-copy orthologs. Leveraging multiple published gene expression datasets from D. melanogaster, and using the cytochrome P450s-a classical detoxification family-as a test case, we demonstrate relationships between xenobiotic induction, detoxification tissue-enriched expression and evolutionary instability in the EcKLs and the P450s. We devised a systematic method for identifying candidate detoxification genes in large gene families that is concordant with experimentally determined functions of P450 genes in D. melanogaster. Applying this method to the EcKLs suggested a significant proportion of these genes play roles in detoxification, and that the EcKLs may constitute a detoxification gene family in insects. Additionally, we estimate that between 11 and 16 uncharacterised D. melanogaster P450s are strong detoxification candidates. Lastly, we also found previously unreported genomic and transcriptomic variation in a number of EcKLs and P450s associated with toxic stress phenotypes using a targeted phenome-wide association study (PheWAS) approach in D. melanogaster, presenting multiple future avenues of research for detoxification genetics in this species.
Assuntos
Drosophila , Ecdisteroides , Animais , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Drosophila/genética , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Ecdisteroides/genética , Ecdisteroides/metabolismo , Perfilação da Expressão Gênica , Genes de Insetos , Genoma de Inseto , Genômica , Insetos , Fosforilação/genética , Fosfotransferases/genética , Fosfotransferases/metabolismo , Filogenia , TranscriptomaRESUMO
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 promise to elucidate the entanglement of gene ontologies, pathways, developmental processes and evolutionary constraints, and inform how these are shaped by adaptation.
Assuntos
Evolução Biológica , Drosophila melanogaster/genética , Adaptação Fisiológica/genética , Animais , Variação Genética , Genoma de Inseto , Insetos/classificação , Insetos/genéticaRESUMO
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 natural populations of Drosophila melanogaster originating from four climate extremes replicated across two continents. Population and quantitative genomic analysis, supported by functional tests, have revealed a mixed genetic architecture to resistance involving major genes (Paramyosin and Nicotinic-Acetylcholine Receptor Alpha 3) and polygenes with a major trade-off with thermotolerance. Reduced genetic differentiation at resistance-associated loci indicated enhanced gene flow at these loci. Resistance alleles showed stronger evidence of positive selection in temperate populations compared to tropical populations in which chromosomal inversions In(2 L)t, In(3 R)Mo and In(3 R)Payne harbour susceptibility alleles. Polygenic architecture and ecological factors should be considered when developing sustainable management strategies for both pest and beneficial insects.
Assuntos
Drosophila melanogaster/fisiologia , Resistência a Inseticidas/fisiologia , Inseticidas , Neonicotinoides , Nitrocompostos , Termotolerância , Animais , Clima , Feminino , Estudo de Associação Genômica Ampla , Receptores Nicotínicos/genética , Tropomiosina/genéticaRESUMO
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; malathion (an organophosphate) and permethrin (a pyrethroid). Genome-wide association studies map survival on malathion to two of the largest sweeps in the D. melanogaster genome; Ace and Cyp6g1 Malathion survivorship also correlates with lines which have high levels of Cyp12d1, Jheh1 and Jheh2 transcript abundance. Permethrin phenotypes map to the largest cluster of P450 genes in the Drosophila genome, however in contrast to a selective sweep driven by insecticide use, the derived allele seems to be associated with susceptibility. These results underscore previous findings that highlight the importance of structural variation to insecticide phenotypes: Cyp6g1 exhibits copy number variation and transposable element insertions, Cyp12d1 is tandemly duplicated, the Jheh loci are associated with a Bari1 transposable element insertion, and a Cyp6a17 deletion is associated with susceptibility.
Assuntos
Drosophila melanogaster/genética , Resistência a Inseticidas/genética , Animais , Animais Geneticamente Modificados , Sistema Enzimático do Citocromo P-450/genética , Variações do Número de Cópias de DNA , Drosophila melanogaster/efeitos dos fármacos , Feminino , Estudo de Associação Genômica Ampla , Inseticidas/toxicidade , Dose Letal Mediana , Malation/toxicidade , Masculino , Permetrina/toxicidade , Fenótipo , TranscriptomaRESUMO
Insecticide resistance is considered a classic model of microevolution, where a strong selective agent is applied to a large natural population, resulting in a change in frequency of alleles that confer resistance. While many insecticide resistance variants have been characterized at the gene level, they are typically single genes of large effect identified in highly resistant pest species. In contrast, multiple variants have been implicated in DDT resistance in Drosophila melanogaster; however, only the Cyp6g1 locus has previously been shown to be relevant to field populations. Here we use genome-wide association studies (GWAS) to identify DDT-associated polygenes and use selective sweep analyses to assess their adaptive significance. We identify and verify two candidate DDT resistance loci. A largely uncharacterized gene, CG10737, has a function in muscles that ameliorates the effects of DDT, while a putative detoxifying P450, Cyp6w1, shows compelling evidence of positive selection.
Assuntos
DDT/toxicidade , Drosophila melanogaster/genética , Loci Gênicos , Resistência a Inseticidas/genética , Praguicidas/toxicidade , Animais , Sistema Enzimático do Citocromo P-450/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/efeitos dos fármacos , Genoma de Inseto , Seleção GenéticaRESUMO
Insecticide resistance is an economically important example of evolution in response to intense selection pressure. Here, the genetics of resistance to the neonicotinoid insecticide imidacloprid is explored using the Drosophila Genetic Reference Panel, a collection of inbred Drosophila melanogaster genotypes derived from a single population in North Carolina. Imidacloprid resistance varied substantially among genotypes, and more resistant genotypes tended to show increased capacity to metabolize and excrete imidacloprid. Variation in resistance level was then associated with genomic and transcriptomic variation, implicating several candidate genes involved in central nervous system function and the cytochrome P450s Cyp6g1 and Cyp6g2. CRISPR-Cas9 mediated removal of Cyp6g1 suggested that it contributed to imidacloprid resistance only in backgrounds where it was already highly expressed. Cyp6g2, previously implicated in juvenile hormone synthesis via expression in the ring gland, was shown to be expressed in metabolically relevant tissues of resistant genotypes. Cyp6g2 overexpression was shown to both metabolize imidacloprid and confer resistance. These data collectively suggest that imidacloprid resistance is influenced by a variety of previously known and unknown genetic factors.
Assuntos
Sistema Enzimático do Citocromo P-450/genética , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/genética , Inseticidas/farmacologia , Neonicotinoides/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Nitrocompostos/farmacologia , Variantes Farmacogenômicos , Animais , Perfilação da Expressão Gênica , Técnicas de Inativação de Genes , Estudo de Associação Genômica Ampla , Haplótipos , Família Multigênica , TranscriptomaRESUMO
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.