Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Using FlyAtlas to identify better Drosophila melanogaster models of human disease


FlyAtlas, a new online resource, provides the most comprehensive view yet of expression in multiple tissues of Drosophila melanogaster. Meta-analysis of the data shows that a significant fraction of the genome is expressed with great tissue specificity in the adult, demonstrating the need for the functional genomic community to embrace a wide range of functional phenotypes. Well-known developmental genes are often reused in surprising tissues in the adult, suggesting new functions. The homologs of many human genetic disease loci show selective expression in the Drosophila tissues analogous to the affected human tissues, providing a useful filter for potential candidate genes. Additionally, the contributions of each tissue to the whole-fly array signal can be calculated, demonstrating the limitations of whole-organism approaches to functional genomics and allowing modeling of a simple tissue fractionation procedure that should improve detection of weak or tissue-specific signals.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Drosophila tissues typically express around half the computed transcriptome.
Figure 2: Evidence for novel transcription units in the Drosophila genome.
Figure 3: Calculating the equation of the fly.


  1. Kaiser, K. From gene to phenotype in Drosophila and other organisms. Bioessays 12, 297–301 (1990).

    Article  CAS  Google Scholar 

  2. Adams, M.D. & Sekelsky, J.J. From sequence to phenotype: reverse genetics in Drosophila melanogaster. Nat. Rev. Genet. 3, 189–198 (2002).

    Article  CAS  Google Scholar 

  3. Orkin, S.H. Reverse genetics and human disease. Cell 47, 845–850 (1986).

    Article  CAS  Google Scholar 

  4. Ruddle, F.H. Reverse genetics as a means of understanding and treating genetic disease. Adv. Neurol. 35, 239–242 (1982).

    CAS  PubMed  Google Scholar 

  5. Bargmann, C.I. High-throughput reverse genetics: RNAi screens in Caenorhabditis elegans. Genome Biol. 2, REVIEWS1005 (2001).

  6. Brown, S.D.M. & Peters, J. Combining mutagenesis and genomics in the mouse–closing the phenotype gap. Trends Genet. 12, 433–435 (1996).

    Article  CAS  Google Scholar 

  7. Bullard, D.C. Mind the phenotype gap. Trends Mol. Med. 7, 537–538 (2001).

    Article  CAS  Google Scholar 

  8. Dow, J.A.T. The Drosophila phenotype gap - and how to close it. Brief. Funct. Genomic. Proteomic. 2, 121–127 (2003).

    Article  CAS  Google Scholar 

  9. Adams, M.D. et al. The genome sequence of Drosophila melanogaster. Science 287, 2185–2195 (2000).

    Article  Google Scholar 

  10. Arbeitman, M.N. et al. Gene expression during the life cycle of Drosophila melanogaster. Science 297, 2270–2275 (2002).

    Article  CAS  Google Scholar 

  11. Andrews, J. et al. Gene discovery using computational and microarray analysis of transcription in the Drosophila melanogaster testis. Genome Res. 10, 2030–2043 (2000).

    Article  CAS  Google Scholar 

  12. Krogh, A. The progress of physiology. Am. J. Physiol. 90, 243–251 (1929).

    Article  Google Scholar 

  13. Brand, A.H. & Perrimon, N. Targetted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118, 401–415 (1993).

    CAS  Google Scholar 

  14. Vandesompele, J. et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 3, RESEARCH0034 (2002).

  15. Stanewsky, R. et al. The cryb mutation identifies cryptochrome as a circadian photoreceptor in Drosophila. Cell 95, 681–692 (1998).

    Article  CAS  Google Scholar 

  16. Emery, P., So, W.V., Kaneko, M., Hall, J.C. & Rosbash, M. CRY, a Drosophila clock and light-regulated cryptochrome, is a major contributor to circadian rhythm resetting and photosensitivity. Cell 95, 669–679 (1998).

    Article  CAS  Google Scholar 

  17. Ivanchenko, M., Stanewsky, R. & Giebultowicz, J.M. Circadian photoreception in Drosophila: functions of cryptochrome in peripheral and central clocks. J. Biol. Rhythms 16, 205–215 (2001).

    Article  CAS  Google Scholar 

  18. Giebultowicz, J.M., Stanewsky, R., Hall, J.C. & Hege, D.M. Transplanted Drosophila excretory tubules maintain circadian clock cycling out of phase with the host. Curr. Biol. 10, 107–110 (2000).

    Article  CAS  Google Scholar 

  19. Carthew, R.W. Adhesion proteins and the control of cell shape. Curr. Opin. Genet. Dev. 15, 358–363 (2005).

    Article  CAS  Google Scholar 

  20. Graham, L.A. & Davies, P.L. The odorant-binding proteins of Drosophila melanogaster: annotation and characterization of a divergent gene family. Gene 292, 43–55 (2002).

    Article  CAS  Google Scholar 

  21. Hekmat-Scafe, D.S., Scafe, C.R., McKinney, A.J. & Tanouye, M.A. Genome-wide analysis of the odorant-binding protein gene family in Drosophila melanogaster. Genome Res. 12, 1357–1369 (2002).

    Article  CAS  Google Scholar 

  22. Dominguez, M., Ferres-Marco, D., Gutierrez-Avino, F.J., Speicher, S.A. & Beneyto, M. Growth and specification of the eye are controlled independently by Eyegone and Eyeless in Drosophila melanogaster. Nat. Genet. 36, 31–39 (2004).

    Article  CAS  Google Scholar 

  23. Aldaz, S., Morata, G. & Azpiazu, N. The Pax-homeobox gene eyegone is involved in the subdivision of the thorax of Drosophila. Development 130, 4473–4482 (2003).

    Article  CAS  Google Scholar 

  24. Jimenez, F. et al. vnd, a gene required for early neurogenesis of Drosophila, encodes a homeodomain protein. EMBO J. 14, 3487–3495 (1995).

    Article  CAS  Google Scholar 

  25. Robinson, D.N. & Cooley, L. Drosophila kelch is an oligomeric ring canal actin organizer. J. Cell Biol. 138, 799–810 (1997).

    Article  CAS  Google Scholar 

  26. Bomont, P. et al. The gene encoding gigaxonin, a new member of the cytoskeletal BTB/kelch repeat family, is mutated in giant axonal neuropathy. Nat. Genet. 26, 370–374 (2000).

    Article  CAS  Google Scholar 

  27. Chien, S., Reiter, L.T., Bier, E. & Gribskov, M. Homophila: human disease gene cognates in Drosophila. Nucleic Acids Res. 30, 149–151 (2002).

    Article  CAS  Google Scholar 

  28. Byers, D., Davis, R.L. & Kiger, J.A. Defect in cyclic AMP phosphodiesterase due to the dunce mutation of learning in Drosophila melanogaster. Nature 289, 79–81 (1981).

    Article  CAS  Google Scholar 

  29. Konopka, R.J. & Benzer, S. Clock mutants of Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 68, 2112–2116 (1971).

    Article  CAS  Google Scholar 

  30. Salkoff, L. & Wyman, R. Genetic modification of potassium channels in Drosophila Shaker mutants. Nature 293, 228–230 (1981).

    Article  CAS  Google Scholar 

  31. Dow, J.A.T. & Davies, S.A. The Malpighian tubule: rapid insights from post-genomic biology. J. Insect Physiol. 52, 365–378 (2006).

    Article  CAS  Google Scholar 

  32. Yang, J. et al. A Drosophila systems approach to xenobiotic metabolism. Physiol. Genomics published online 8 May 2007 (doi:10.1152/physiolgenomics.00018.2007).

    Article  CAS  Google Scholar 

  33. McGettigan, J. et al. Insect renal tubules constitute a cell-autonomous immune system that protects the organism against bacterial infection. Insect Biochem. Mol. Biol. 35, 741–754 (2005).

    Article  CAS  Google Scholar 

  34. Kaneko, T. et al. PGRP-LC and PGRP-LE have essential yet distinct functions in the Drosophila immune response to monomeric DAP-type peptidoglycan. Nat. Immunol. 7, 715–723 (2006).

    Article  CAS  Google Scholar 

  35. Davies, S.A. et al. Analysis and inactivation of vha55, the gene encoding the V-ATPase B-subunit in Drosophila melanogaster, reveals a larval lethal phenotype. J. Biol. Chem. 271, 30677–30684 (1996).

    Article  CAS  Google Scholar 

  36. Allan, A.K., Du, J., Davies, S.A. & Dow, J.A.T. Genome-wide survey of V-ATPase genes in Drosophila reveals a conserved renal phenotype for lethal alleles. Physiol. Genomics 22, 128–138 (2005).

    Article  CAS  Google Scholar 

  37. Karet, F.E. et al. Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness. Nat. Genet. 21, 84–90 (1999).

    Article  CAS  Google Scholar 

  38. Evans, J.M., Allan, A.K., Davies, S.A. & Dow, J.A.T. Sulphonylurea sensitivity and enriched expression implicate inward rectifier K+ channels in Drosophila melanogaster renal function. J. Exp. Biol. 208, 3771–3783 (2005).

    Article  CAS  Google Scholar 

  39. Glassman, E. & Mitchell, H.K. Mutants of Drosophila melanogaster deficient in xanthine dehydrogenase. Genetics 44, 153–162 (1959).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Dent, C.E. & Philpot, G.R. Xanthinuria: an inborn error of metabolism. Lancet 263, 182–185 (1954).

    Article  Google Scholar 

  41. Wang, J. et al. Function-informed transcriptome analysis of Drosophila renal tubule. Genome Biol. 5, R69 (2004).

    Article  Google Scholar 

  42. Dow, J.A.T. & Davies, S.A. Integrative physiology and functional genomics of epithelial function in a genetic model organism. Physiol. Rev. 83, 687–729 (2003).

    Article  CAS  Google Scholar 

  43. Yang, Z., Edenberg, H.J. & Davis, R.L. Isolation of mRNA from specific tissues of Drosophila by mRNA tagging. Nucleic Acids Res. 33, e148 (2005).

    Article  Google Scholar 

  44. Manak, J.R. et al. Biological function of unannotated transcription during the early development of Drosophila melanogaster. Nat. Genet. 38, 1151–1158 (2006).

    Article  CAS  Google Scholar 

Download references


This work was funded by the UK's Biotechnology and Biological Sciences Research Council (BBSRC). We are most grateful to S. Terhzaz, P. Cabrero and L. Aitchison for their guidance in dissections and S.-A. Davies and S. Goodwin for their critical reading of the manuscript.

Author information

Authors and Affiliations


Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

Genes that are expressed in a single tissue in adult Drosophila. (PDF 41 kb)

Supplementary Table 2

Genes that show invariant expression between tissues. (PDF 32 kb)

Supplementary Table 3

Array probe sets against unannotated regions of the genome that show significant expression. (PDF 101 kb)

Supplementary Methods (PDF 86 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Chintapalli, V., Wang, J. & Dow, J. Using FlyAtlas to identify better Drosophila melanogaster models of human disease. Nat Genet 39, 715–720 (2007).

Download citation

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing