Article

The Drosophila melanogaster Genetic Reference Panel.

Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695, USA.
Nature (Impact Factor: 42.35). 02/2012; 482(7384):173-8. DOI: 10.1038/nature10811
Source: PubMed

ABSTRACT A major challenge of biology is understanding the relationship between molecular genetic variation and variation in quantitative traits, including fitness. This relationship determines our ability to predict phenotypes from genotypes and to understand how evolutionary forces shape variation within and between species. Previous efforts to dissect the genotype-phenotype map were based on incomplete genotypic information. Here, we describe the Drosophila melanogaster Genetic Reference Panel (DGRP), a community resource for analysis of population genomics and quantitative traits. The DGRP consists of fully sequenced inbred lines derived from a natural population. Population genomic analyses reveal reduced polymorphism in centromeric autosomal regions and the X chromosome, evidence for positive and negative selection, and rapid evolution of the X chromosome. Many variants in novel genes, most at low frequency, are associated with quantitative traits and explain a large fraction of the phenotypic variance. The DGRP facilitates genotype-phenotype mapping using the power of Drosophila genetics.

Download full-text

Full-text

Available from: Julio Rozas, Jun 28, 2015
1 Follower
 · 
349 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Both malnutrition and undernutrition can lead to compromised immune defense in a diversity of animals, and "nutritional immunology" has been suggested as a means of understanding immunity and determining strategies for fighting infection. The genetic basis for the effects of diet on immunity, however, has been largely unknown. In the present study, we have conducted genome-wide association mapping in Drosophila melanogaster to identify the genetic basis for individual variation in resistance, and for variation in immunological sensitivity to diet (genotype-by-environment interaction, or GxE). D. melanogaster were reared for several generations on either high-glucose or low-glucose diets and then infected with Providencia rettgeri, a natural bacterial pathogen of D. melanogaster. Systemic pathogen load was measured at the peak of infection intensity, and several indicators of nutritional status were taken from uninfected flies reared on each diet. We find that dietary glucose level significantly alters the quality of immune defense, with elevated dietary glucose resulting in higher pathogen loads. The quality of immune defense is genetically variable within the sampled population, and we find genetic variation for immunological sensitivity to dietary glucose (genotype-by-diet interaction). Immune defense was genetically correlated with indicators of metabolic status in flies reared on the high-glucose diet, and we identified multiple genes that explain variation in immune defense, including several that have not been previously implicated in immune response but which are confirmed to alter pathogen load after RNAi knockdown. Our findings emphasize the importance of dietary composition to immune defense and reveal genes outside the conventional "immune system" that can be important in determining susceptibility to infection. Functional variation in these genes is segregating in a natural population, providing the substrate for evolutionary response to pathogen pressure in the context of nutritional environment.
    PLoS Genetics 03/2015; 11(3):e1005030. DOI:10.1371/journal.pgen.1005030 · 8.17 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cactophilic Drosophila species provide a valuable model to study gene-environment interactions and ecological adaptation. D. buzzatii and D. mojavensis are two cactophilic species that belong to the repleta group, but have very different geographical distributions and primary host plants. To investigate the genomic basis of ecological adaptation, we sequenced the genome and developmental transcriptome of D. buzzatii and compared its gene content to that of D. mojavensis and two other non-cactophilic Drosophila species in the same subgenus. The newly sequenced D. buzzatii genome (161.5 Mb) comprises 826 scaffolds (> 3 kb) and contains 13,657 annotated protein-coding genes. Using RNA-Seq data of five life-stages we found expression of 15,026 genes, 80% protein-coding genes and 20% ncRNA genes. In total, we detected 1,294 genes putatively under positive selection. Interestingly, among genes under positive selection in the D. mojavensis lineage, there is an excess of genes involved in metabolism of heterocyclic compounds that are abundant in Stenocereus cacti and toxic to nonresident Drosophila species. We found 117 orphan genes in the shared D. buzzatii-D. mojavensis lineage. In addition, gene duplication analysis identified lineage-specific expanded families with functional annotations associated with proteolysis, zinc ion binding, chitin binding, sensory perception, ethanol tolerance, immunity, physiology and reproduction. In summary we identified genetic signatures of adaptation in the shared D. buzzatii-D. mojavensis lineage, and in the two separate D. buzzatii and D. mojavensis lineages. Many of the novel lineage-specific genomic features are promising candidates for explaining the adaptation of these species to their distinct ecological niches. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
    Genome Biology and Evolution 01/2015; 7(1). DOI:10.1093/gbe/evu291 · 4.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Widespread premature termination codon mutations (PTCs) were recently observed in human and fly populations. We took advantage of the population resequencing data in the Drosophila Genetic Reference Panel (DGRP) to investigate how the expression profile and the evolutionary age of genes shaped the allele frequency distribution of PTCs. After generating a high-quality dataset of PTCs, we clustered genes harboring PTCs into three categories: genes encoding low-frequency PTCs (≤ 1.5%), moderate-frequency PTCs (1.5%-10%) and high-frequency PTCs (> 10%). All three groups show narrow transcription compared to PTC-free genes, with the moderate- and high-PTC frequency groups showing a pronounced pattern. Moreover, nearly half (42%) of the PTC-encoding genes are not expressed in any tissue. Interestingly, the moderate-frequency PTC group is strongly enriched for genes expressed in midgut, whereas genes harboring high-frequency PTCs tend to have sex-specific expression. We further find that although young genes born in the last 60 million years (Myr) compose a mere 9% of the genome, they represent 16%, 30% and 50% of the genes containing low-, moderate- and high-frequency PTCs, respectively. Among DNA-based and RNA-based duplicated genes, the child copy is approximately twice as likely to contain PTCs as the parent copy, whereas young de novo genes are as likely to encode PTCs as DNA-based duplicated new genes. Based on these results, we conclude that expression profile and gene age jointly shaped the landscape of PTC-mediated gene loss. Therefore, we propose that new genes may need a long time to become stably maintained after the origination.
    Molecular Biology and Evolution 11/2014; 32(1). DOI:10.1093/molbev/msu299 · 14.31 Impact Factor