scholarly journals Cis and trans-acting variants contribute to survivorship in a naïve Drosophila melanogaster population exposed to ryanoid insecticides

2018 ◽  
Author(s):  
Llewellyn Green ◽  
Paul Battlay ◽  
Alexandre Fournier-Level ◽  
Robert T. Good ◽  
Charles Robin
Keyword(s):  
Drosophila Melanogaster ◽  
Insecticide Resistance ◽  
Allelic Variation ◽  
Association Studies ◽  
Natural Populations ◽  
Intermediate Frequency ◽  
Genome Wide Association ◽  
Systems Genetics ◽  
Genome Wide Association Studies ◽  
Genome Wide

AbstractInsecticide 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 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. Genome-wide association studies 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 homologue 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 adumbrates a selective response among natural populations to these chemicals.SignificanceAround the world insecticides are being deregistered and banned, as their environmental costs are deemed too great or their efficacy against pest insects is reduced through the evolution of insecticide resistance. With the introduction of replacement insecticides comes the responsibility to assess the way new insecticides perturb various levels of biological systems; from insect physiology to ecosystems. We used a systems genetics approach to identify genetic variants affecting survivorship of Drosophila melanogaster exposed to chlorantraniliprole. The study population was completely naïve to this insecticide chemistry and yet we find associations with variants in neuromuscular genes and co-regulated detoxification genes. We predict that these variants will increase in populations of this ‘sentinel species’ as these insecticides are applied in the environment.

scholarly journals Cis- and trans-acting variants contribute to survivorship in a naïve Drosophila melanogaster population exposed to ryanoid insecticides

2019 ◽  
Vol 116 (21) ◽  
pp. 10424-10429 ◽  
Author(s):  
Llewellyn Green ◽  
Paul Battlay ◽  
Alexandre Fournier-Level ◽  
Robert T. Good ◽  
Charles Robin
Keyword(s):  
Drosophila Melanogaster ◽  
Allelic Variation ◽  
Association Studies ◽  
Natural Populations ◽  
Intermediate Frequency ◽  
Major Effect ◽  
Genome Wide Association Studies ◽  
Multiple Transcripts ◽  
Number Variation ◽  
Cis And Trans

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.

scholarly journals Genome-wide genetic data on ~500,000 UK Biobank participants

2017 ◽  
Author(s):  
Clare Bycroft ◽  
Colin Freeman ◽  
Desislava Petkova ◽  
Gavin Band ◽  
Lloyd T. Elliott ◽  
...  
Keyword(s):  
Quality Control ◽  
Allelic Variation ◽  
Association Studies ◽  
Genetic Data ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genotype Data ◽  
Uk Biobank ◽  
Genome Wide ◽  
Wide Range

AbstractThe UK Biobank project is a large prospective cohort study of ~500,000 individuals from across the United Kingdom, aged between 40-69 at recruitment. A rich variety of phenotypic and health-related information is available on each participant, making the resource unprecedented in its size and scope. Here we describe the genome-wide genotype data (~805,000 markers) collected on all individuals in the cohort and its quality control procedures. Genotype data on this scale offers novel opportunities for assessing quality issues, although the wide range of ancestries of the individuals in the cohort also creates particular challenges. We also conducted a set of analyses that reveal properties of the genetic data – such as population structure and relatedness – that can be important for downstream analyses. In addition, we phased and imputed genotypes into the dataset, using computationally efficient methods combined with the Haplotype Reference Consortium (HRC) and UK10K haplotype resource. This increases the number of testable variants by over 100-fold to ~96 million variants. We also imputed classical allelic variation at 11 human leukocyte antigen (HLA) genes, and as a quality control check of this imputation, we replicate signals of known associations between HLA alleles and many common diseases. We describe tools that allow efficient genome-wide association studies (GWAS) of multiple traits and fast phenome-wide association studies (PheWAS), which work together with a new compressed file format that has been used to distribute the dataset. As a further check of the genotyped and imputed datasets, we performed a test-case genome-wide association scan on a well-studied human trait, standing height.

scholarly journals The power of a multivariate approach to genome-wide association studies: an example with Drosophila melanogaster wing shape

2017 ◽  
Author(s):  
William Pitchers ◽  
Jessica Nye ◽  
Eladio J. Márquez ◽  
Alycia Kowalski ◽  
Ian Dworkin ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Multivariate Analyses ◽  
Association Studies ◽  
Significant Snps ◽  
Wing Shape ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Phenotypic Effect ◽  
Genome Wide ◽  
Univariate Analyses

AbstractDue to the complexity of genotype-phenotype relationships, simultaneous analyses of genomic associations with multiple traits will be more powerful and more informative than a series of univariate analyses. In most cases, however, studies of genotype-phenotype relationships have analyzed only one trait at a time, even as the rapid advances in molecular tools have expanded our view of the genotype to include whole genomes. Here, we report the results of a fully integrated multivariate genome-wide association analysis of the shape of the Drosophila melanogaster wing in the Drosophila Genetic Reference Panel. Genotypic effects on wing shape were highly correlated between two different labs. We found 2,396 significant SNPs using a 5% FDR cutoff in the multivariate analyses, but just 4 significant SNPs in univariate analyses of scores on the first 20 principal component axes. A key advantage of multivariate analysis is that the direction of the estimated phenotypic effect is much more informative than a univariate one. Exploiting this feature, we show that the directions of effects were on average replicable in an unrelated panel of inbred lines. Effects of knockdowns of genes implicated in the initial screen were on average more similar than expected under a null model. Association studies that take a phenomic approach in considering many traits simultaneously are an important complement to the power of genomics. Multivariate analyses of such data are more powerful, more informative, and allow the unbiased study of pleiotropy.

scholarly journals Increasing the power of genome wide association studies in natural populations using repeated measures – evaluation and implementation

2016 ◽  
Vol 7 (7) ◽  
pp. 792-799 ◽  
Author(s):  
Lars Rönnegård ◽  
S. Eryn McFarlane ◽  
Arild Husby ◽  
Takeshi Kawakami ◽  
Hans Ellegren ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Association Studies ◽  
Natural Populations ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

scholarly journals The genetic basis of cooperation and conflict in natural populations of a model symbiont

2021 ◽  
Author(s):  
Rebecca T Batstone ◽  
Liana T Burghardt ◽  
Katy D Heath
Keyword(s):  
Nucleotide Diversity ◽  
Genetic Basis ◽  
Balancing Selection ◽  
Association Studies ◽  
Natural Populations ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Ensifer Meliloti ◽  
Single Versus

Although mutualisms are defined as net beneficial interactions among species, whether fitness conflict or alignment drive the evolution of these interactions is unclear. Examining the relationships between host and symbiont fitness proxies at both the organismal and genomic levels can provide new insights. Here, we utilized data from several genome-wide association studies (GWAS) that involved 191 strains of the N-fixing rhizobium symbiont, Ensifer meliloti, collected from natural populations being paired in single or mixed inoculation with two genotypes of the host Medicago truncatula to determine how different proxies of microbial fitness were related to one another, and examine signatures of fitness conflict and alignment between host and symbiont at both the whole-organism and genomic levels. We found little evidence for fitness conflict; instead, loci tended to have concordant effects on both host and symbiont fitness and showed heightened nucleotide diversity and signatures of balancing selection compared to the rest of the genome. We additionally found that single versus competitive measures of rhizobium fitness are distinct, and that the latter should be used given that they better reflect the ecological conditions rhizobia experience in nature. Our results suggest that although conflict appears to be largely resolved in natural populations of rhizobia, mutualistic coevolution between legumes and rhizobia can nonetheless maintain genetic diversity, potentially explaining why variation in symbiotic traits persists in nature.

scholarly journals Spatiotemporal patterns of desiccation tolerance in natural populations of Drosophila melanogaster

2016 ◽  
Author(s):  
Subhash Rajpurohit ◽  
Eran Gefen ◽  
Alan Bergland ◽  
Dmitri Petrov ◽  
Allen G Gibbs ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Drought Tolerance ◽  
North American ◽  
Desiccation Tolerance ◽  
Experimental Evolution ◽  
Association Studies ◽  
Natural Populations ◽  
Genome Wide Association Studies ◽  
Physiological Basis ◽  
Genome Wide

AbstractWater availability is a major environmental challenge to a variety of terrestrial organisms. In insects, desiccation tolerance varies predictably over various spatial and temporal scales and is an important physiological basis of fitness variation among natural populations. Here, we examine the dynamics of desiccation tolerance in North American populations of Drosophila melanogaster using: 1) natural populations sampled across latitudes and seasons in the eastern USA; 2) experimental evolution in the field in response to changing seasonal environments; 3) a sequenced panel of inbred lines (DGRP) to perform genome wide associations and examine whether SNPs/genes associated with variation in desiccation tolerance exhibit patterns of clinal and/or seasonal enrichment in pooled sequencing of populations. In natural populations we observed a shallow cline in desiccation tolerance, for which tolerance exhibited a positive association with latitude; the steepness of this cline increased with decreasing culture temperature, demonstrating a significant degree of thermal plasticity. No differences in desiccation tolerance were observed between spring and autumn collections from three mid-to-northern latitude populations, or as a function of experimental evolution to seasonality. Similarly, water loss rates did not vary significantly among latitudinal, seasonal or experimental evolution populations. However, changes in metabolic rates during prolonged exposure to dry conditions indicate increased tolerance in higher latitude populations. Genome wide association studies identified thirty-six SNPs in twenty-eight genes associated with sex-averaged drought tolerance. Among North American populations, genes associated with drought tolerance do not show increased signatures of spatially varying selection relative to the rest of the genome, whereas among Australian populations they do.

scholarly journals Genome-Wide Association Studies Reveal a Simple Genetic Basis of Resistance to Naturally Coevolving Viruses in Drosophila melanogaster

PLoS Genetics ◽  
2012 ◽  
Vol 8 (11) ◽  
pp. e1003057 ◽  
Author(s):  
Michael M. Magwire ◽  
Daniel K. Fabian ◽  
Hannah Schweyen ◽  
Chuan Cao ◽  
Ben Longdon ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Genetic Basis ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

scholarly journals Population structure of the Brachypodium species complex and genome wide association of agronomic traits in response to climate

2018 ◽  
Author(s):  
Pip Wilson ◽  
Jared Streich ◽  
Kevin Murray ◽  
Steve Eichten ◽  
Riyan Cheng ◽  
...  
Keyword(s):  
Species Complex ◽  
Agronomic Traits ◽  
Association Studies ◽  
Genomic Structure ◽  
Natural Populations ◽  
Climatic Conditions ◽  
Model Systems ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

AbstractThe development of model systems requires a detailed assessment of standing genetic variation across natural populations. The Brachypodium species complex has been promoted as a plant model for grass genomics with translational to small grain and biomass crops. To capture the genetic diversity within this species complex, thousands of Brachypodium accessions from around the globe were collected and sequenced using genotyping by sequencing (GBS). Overall, 1,897 samples were classified into two diploid or allopolyploid species and then further grouped into distinct inbred genotypes. A core set of diverse B. distachyon diploid lines were selected for whole genome sequencing and high resolution phenotyping. Genome-wide association studies across simulated seasonal environments was used to identify candidate genes and pathways tied to key life history and agronomic traits under current and future climatic conditions. A total of 8, 22 and 47 QTLs were identified for flowering time, early vigour and energy traits, respectively. Overall, the results highlight the genomic structure of the Brachypodium species complex and allow powerful complex trait dissection within this new grass model species.

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