The Drosophila melanogaster Genetic Reference Panel

Journal name:
Nature
Volume:
482,
Pages:
173–178
Date published:
DOI:
doi:10.1038/nature10811
Received
Accepted
Published online

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.

At a glance

Figures

  1. SNP variation in the DGRP lines.
    Figure 1: SNP variation in the DGRP lines.

    a, Site frequency spectrum. b, Numbers of SNPs per site class. c, Decay of linkage disequilibrium (r2) with physical distance for the five major chromosome arms. d, Lack of population structure. The red curve depicts the ranked eigenvalues of the genetic covariance matrix in decreasing order with respect to the marginal variance explained; the blue curve shows their cumulative sum as a fraction of the total with respect to cumulative variance explained. The partitioning of total genetic variance is balanced among the eigenvectors. The principal eigenvector explains <1.1% of the total genetic variance.

  2. Pattern of polymorphism, divergence, [agr] and recombination rate along chromosome arms in non-overlapping 50-kbp windows.
    Figure 2: Pattern of polymorphism, divergence, α and recombination rate along chromosome arms in non-overlapping 50-kbp windows.

    a, Nucleotide polymorphism (π). The solid curves give the recombination rate (cMMb−1). b, Divergence (k) for D. simulans (light green) and D. yakuba (dark green). c, Polymorphism to divergence ratio (Pol/Div), estimated as 1[(π0-fold/π4-fold)/(k0-fold/k4-fold)]. An excess of 0-fold divergence relative to polymorphism (k0-fold/k4-fold)>(π0-fold/π4-fold) is interpreted as adaptive fixation whereas an excess of 0-fold polymorphism relative to divergence (π0-fold/π4-fold)>(k0-fold/k4-fold) indicates that weakly deleterious or nearly neutral mutations are segregating in the population.

  3. The fraction of alleles segregating under different selection regimes by site class and chromosome region, for the autosomes (A) and the X chromosome (X).
    Figure 3: The fraction of alleles segregating under different selection regimes by site class and chromosome region, for the autosomes (A) and the X chromosome (X).

    The selection regimes are strongly deleterious (d, dark blue), weakly deleterious (b, blue), recently neutral (γ, white) and old neutral (fγ, light blue). Each chromosome arm has been divided in three regions of equal size (in Mb): centromere, middle and telomere.

  4. Genotype-phenotype associations for starvation resistance.
    Figure 4: Genotype–phenotype associations for starvation resistance.

    a, Genome-wide association results for significant SNPs. The lower triangle depicts linkage disequilibrium (r2) among SNPs, with the five major chromosome arms demarcated by black lines. The upper panels give the significance threshold (−log(p), uncorrected for multiple tests), the effect in phenotypic standard deviation units, and the minor allele frequency (MAF). b, c, Partial least squares regressions of phenotypes predicted using SNP data on observed phenotypes. The blue dots represent the predicted and observed phenotypes of lines that were not included in the initial study. b, Females (r2 = 0.81); c, males (r2 = 0.85).

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Author information

  1. These authors contributed equally to this work.

    • Trudy F. C. Mackay,
    • Stephen Richards,
    • Eric A. Stone &
    • Antonio Barbadilla

Affiliations

  1. Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695, USA

    • Trudy F. C. Mackay,
    • Eric A. Stone,
    • Julien F. Ayroles,
    • Michael M. Magwire,
    • Mary Anna Carbone,
    • Laura Duncan,
    • Zeke Harris,
    • Katherine W. Jordan,
    • Faye Lawrence,
    • Richard F. Lyman,
    • Stephanie M. Rollmann,
    • Lavanya Turlapati &
    • Akihiko Yamamoto
  2. Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030 USA

    • Stephen Richards,
    • Dianhui Zhu,
    • Yi Han,
    • Crystal Bess,
    • Kerstin Petra Blankenburg,
    • Lesley Chaboub,
    • Mehwish Javaid,
    • Joy Christina Jayaseelan,
    • Shalini N. Jhangiani,
    • Fremiet Lara,
    • Sandra L. Lee,
    • Mala Munidasa,
    • Donna Marie Muzny,
    • Lynne Nazareth,
    • Irene Newsham,
    • Lora Perales,
    • Ling-Ling Pu,
    • Carson Qu,
    • Jeffrey G. Reid,
    • Nehad Saada,
    • Kim C. Worley,
    • Yuan-Qing Wu,
    • Yiming Zhu &
    • Richard A. Gibbs
  3. Genomics, Bioinformatics and Evolution Group, Institut de Biotecnologia i de Biomedicina - IBB/Department of Genetics and Microbiology, Campus Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain

    • Antonio Barbadilla,
    • Sònia Casillas,
    • Maite Barrón,
    • David Castellano &
    • Miquel Ràmia
  4. Department of Ecology and Evolutionary Biology, University of California - Irvine, Irvine, California 92697, USA

    • Julie M. Cridland &
    • Kevin R. Thornton
  5. Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK

    • Mark F. Richardson,
    • Raquel S. Linheiro &
    • Casey M. Bergman
  6. Department of Biology, North Carolina State University, Raleigh, North Carolina 27695, USA

    • Robert R. H. Anholt
  7. Molecular Evolutionary Genetics Group, Department of Genetics, Faculty of Biology, Universitat de Barcelona, Diagonal 645, 08028 Barcelona, Spain

    • Pablo Librado &
    • Julio Rozas
  8. Center for Public Health Genomics, University of Virginia, PO Box 800717, Charlottesville, Virginia 22908, USA

    • Aaron J. Mackey
  9. Virginia Bioinformatics Institute and Department of Biological Sciences, Virginia Tech, Blacksburg, Virginia 24061, USA

    • David Mittelman
  10. Present addresses: FAS Society of Fellows, Harvard University, 78 Mt Auburn Street, Cambridge, Massachusetts 02138, USA (J.F.A.) ; Functional Comparative Genomics Group, Institut de Biotecnologia i de Biomedicina - IBB, Campus Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain (S.C.); Department of Biological Sciences, University of Cincinnati, Cincinnati, Ohio 45221, USA (S.M.R.).

    • Julien F. Ayroles,
    • Sònia Casillas &
    • Stephanie M. Rollmann

Contributions

T.F.C.M., S.R. and R.A.G. conceived the project. T.F.C.M., S.R., A.B. and E.A.S. wrote the main manuscript. T.F.C.M., S.R., A.B., E.A.S., J.F.A., K.R.T., J.M.C., C.M.B. and D.M. wrote the Supplementary methods. M.M.M., C.B., K.P.B., M.A.C., L.C., L.D., Y.H., M.J., J.C.J., S.N.J., K.W.J., F. Lara, F. Lawrence, S.L.L., R.F.L., M.M., D.M.M., L.N., I.M., L.P., L.L.P., C.Q., J.G.R., S.M.R., L.T., K.C.W., Y.-Q.W., A.Y. and Y.Z. performed experiments. T.F.C.M., A.B., J.F.A., D.Z., S.C., M.M.M., J.M.C., M.F.R., M.B., D.C., R.S.L., A.M., C.M.B., K.R.T., D.M. and E.A.S. did the bioinformatics and data analysis. J.F.A., S.C., M.M.M., Z.H., P.L., M.R., J.R. and E.A.S. wrote the Methods and did the web site development. R.R.H.A. contributed resources.

Competing financial interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to:

Sequences have been deposited at the National Center for Biotechnology Information Short Read Archives (http://www.ncbi.nlm.nih.gov/sra?term=DGRP).

Author details

Supplementary information

PDF files

  1. Supplementary Information (360K)

    This file contains Supplementary Methods and Data (see Contents for more details) and Supplementary References.

  2. Supplementary Figures (2M)

    This file contains Supplementary Figures 1-16 with legends.

  3. Supplementary Tables (6.4M)

    This file contains Supplementary Tables 1-17, 19-22 and 25-28 – see separate files for Supplementary Tables 18, 23 and 24.

Excel files

  1. Supplementary Table 18 (72K)

    This file contains GO categories, selective constraint and positive selection.

  2. Supplementary Table 23 (392K)

    This file contains GWA analysis results.

  3. Supplementary Table 24 (64K)

    This file contains Microsatellite analysis results.

Additional data