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Systems genetics of complex traits in Drosophila melanogaster

Nature Genetics volume 41, pages 299–307 (2009)Cite this article

Abstract

Determining the genetic architecture of complex traits is challenging because phenotypic variation arises from interactions between multiple, environmentally sensitive alleles. We quantified genome-wide transcript abundance and phenotypes for six ecologically relevant traits in D. melanogaster wild-derived inbred lines. We observed 10,096 genetically variable transcripts and high heritabilities for all organismal phenotypes. The transcriptome is highly genetically intercorrelated, forming 241 transcriptional modules. Modules are enriched for transcripts in common pathways, gene ontology categories, tissue-specific expression and transcription factor binding sites. The high degree of transcriptional connectivity allows us to infer genetic networks and the function of predicted genes from annotations of other genes in the network. Regressions of organismal phenotypes on transcript abundance implicate several hundred candidate genes that form modules of biologically meaningful correlated transcripts affecting each phenotype. Overlapping transcripts in modules associated with different traits provide insight into the molecular basis of pleiotropy between complex traits.

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Figure 1: Variation in transcript abundance among 40 wild-derived inbred lines.
Figure 2: Correlated transcriptional modules.
Figure 3: Biology of transcriptional modules.
Figure 4: Variation for organismal phenotypes among 40 wild-derived inbred lines.
Figure 5: Distribution of SFP effects.
Figure 6: Effects of P-element mutations in candidate genes affecting quantitative traits.
Figure 7: Modules of correlated transcripts associated with organismal phenotypes.
Figure 8: Pleiotropy between phenotypic modules.

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Acknowledgements

This work was supported by grants from the National Institutes of Health (R01 GM 45146, R01 GM 076083, R01 AA016560 to T.F.C.M. and R01 GM 59469 to R.R.H.A.). The authors thank S. Heinsohn for technical assistance. This is a publication of the W. M. Keck Center for Behavioral Biology.

Author information

Author notes

  1. Michael M Magwire & Stephanie M Rollmann

    Present address: Present addresses: Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK (M.M.M.) and Department of Biological Sciences, University of Cincinnati, PO Box 210006, 614 Rieveschl Hall, Cincinnati, Ohio 45221, USA (S.M.R.).,

  2. Julien F Ayroles, Mary Anna Carbone and Eric A Stone: These authors contributed equally to this work.

Authors and Affiliations

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

    Julien F Ayroles, Mary Anna Carbone, Katherine W Jordan, Richard F Lyman, Michael M Magwire, Stephanie M Rollmann, Laura H Duncan, Faye Lawrence, Robert R H Anholt & Trudy F C Mackay

  2. W. M. Keck Center for Behavioral Biology, North Carolina State University, Raleigh, 27695, North Carolina, USA

    Julien F Ayroles, Mary Anna Carbone, Katherine W Jordan, Richard F Lyman, Michael M Magwire, Stephanie M Rollmann, Laura H Duncan, Faye Lawrence, Robert R H Anholt & Trudy F C Mackay

  3. Department of Statistics, North Carolina State University, Raleigh, 27695, North Carolina, USA

    Eric A Stone

  4. Department of Biology, North Carolina State University, Raleigh, 27695, North Carolina, USA

    Robert R H Anholt

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Contributions

T.F.C.M., J.F.A., E.A.S. and R.R.H.A. wrote the paper. R.F.L. constructed the Drosophila lines. M.A.C. obtained the gene expression data. K.W.J., M.M.M., S.M.R., L.H.D. and F.L. obtained the organismal phenotype data. J.F.A., E.A.S. and K.W.J. performed the statistical analyses.

Corresponding author

Correspondence to Trudy F C Mackay.

Supplementary information

Supplementary Table 1

Quantitative genetic analyses of variation for 14,480 expressed transcripts in 40 wild-derived inbred lines. Expression is measured as the median log2 intensity of PM transcripts in each probe set that do not contain SFPs. (XLS 5595 kb)

Supplementary Table 2

Over-representation of Gene Ontology Categories, KEGG Pathways and KOG Ontologies for two-fold male and female biased transcripts, transcripts with high (> 0.8) and low (< 0.2) broad sense heritabilities (H2), and transcripts with low (< 0.2) cross-sex genetic correlations (rMF). (XLS 134 kb)

Supplementary Table 3

Enrichment of transcription factor motifs in 5′ UTR sequences of genes in modules of correlated transcripts. (XLS 251 kb)

Supplementary Table 4

Quantitative genetics of organismal phenotypes for 40 wild-derived inbred lines. (PDF 157 kb)

Supplementary Table 5

Associations of SFPs with quantitative traits. (XLS 291 kb)

Supplementary Table 6

Transcripts and modules of correlated transcripts associated with each of six quantitative traits. (XLS 985 kb)

Supplementary Table 7

Effects of P[GT1] insertional mutations in candidate genes affecting resistance to starvation stress and chill coma recovery time. (XLS 96 kb)

Supplementary Table 8

Over-representation of Gene Ontology Categories, KEGG Pathways and Keywords for transcripts associated with quantitative trait phenotypes. (XLS 188 kb)

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Ayroles, J., Carbone, M., Stone, E. et al. Systems genetics of complex traits in Drosophila melanogaster. Nat Genet 41, 299–307 (2009). https://doi.org/10.1038/ng.332

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