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.
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Kaiser, K. From gene to phenotype in Drosophila and other organisms. Bioessays 12, 297–301 (1990).
Adams, M.D. & Sekelsky, J.J. From sequence to phenotype: reverse genetics in Drosophila melanogaster. Nat. Rev. Genet. 3, 189–198 (2002).
Orkin, S.H. Reverse genetics and human disease. Cell 47, 845–850 (1986).
Ruddle, F.H. Reverse genetics as a means of understanding and treating genetic disease. Adv. Neurol. 35, 239–242 (1982).
Bargmann, C.I. High-throughput reverse genetics: RNAi screens in Caenorhabditis elegans. Genome Biol. 2, REVIEWS1005 (2001).
Brown, S.D.M. & Peters, J. Combining mutagenesis and genomics in the mouse–closing the phenotype gap. Trends Genet. 12, 433–435 (1996).
Bullard, D.C. Mind the phenotype gap. Trends Mol. Med. 7, 537–538 (2001).
Dow, J.A.T. The Drosophila phenotype gap - and how to close it. Brief. Funct. Genomic. Proteomic. 2, 121–127 (2003).
Adams, M.D. et al. The genome sequence of Drosophila melanogaster. Science 287, 2185–2195 (2000).
Arbeitman, M.N. et al. Gene expression during the life cycle of Drosophila melanogaster. Science 297, 2270–2275 (2002).
Andrews, J. et al. Gene discovery using computational and microarray analysis of transcription in the Drosophila melanogaster testis. Genome Res. 10, 2030–2043 (2000).
Krogh, A. The progress of physiology. Am. J. Physiol. 90, 243–251 (1929).
Brand, A.H. & Perrimon, N. Targetted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118, 401–415 (1993).
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).
Stanewsky, R. et al. The cryb mutation identifies cryptochrome as a circadian photoreceptor in Drosophila. Cell 95, 681–692 (1998).
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).
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).
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).
Carthew, R.W. Adhesion proteins and the control of cell shape. Curr. Opin. Genet. Dev. 15, 358–363 (2005).
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).
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).
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).
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).
Jimenez, F. et al. vnd, a gene required for early neurogenesis of Drosophila, encodes a homeodomain protein. EMBO J. 14, 3487–3495 (1995).
Robinson, D.N. & Cooley, L. Drosophila kelch is an oligomeric ring canal actin organizer. J. Cell Biol. 138, 799–810 (1997).
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).
Chien, S., Reiter, L.T., Bier, E. & Gribskov, M. Homophila: human disease gene cognates in Drosophila. Nucleic Acids Res. 30, 149–151 (2002).
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).
Konopka, R.J. & Benzer, S. Clock mutants of Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 68, 2112–2116 (1971).
Salkoff, L. & Wyman, R. Genetic modification of potassium channels in Drosophila Shaker mutants. Nature 293, 228–230 (1981).
Dow, J.A.T. & Davies, S.A. The Malpighian tubule: rapid insights from post-genomic biology. J. Insect Physiol. 52, 365–378 (2006).
Yang, J. et al. A Drosophila systems approach to xenobiotic metabolism. Physiol. Genomics published online 8 May 2007 (doi:10.1152/physiolgenomics.00018.2007).
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).
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).
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).
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).
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).
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).
Glassman, E. & Mitchell, H.K. Mutants of Drosophila melanogaster deficient in xanthine dehydrogenase. Genetics 44, 153–162 (1959).
Dent, C.E. & Philpot, G.R. Xanthinuria: an inborn error of metabolism. Lancet 263, 182–185 (1954).
Wang, J. et al. Function-informed transcriptome analysis of Drosophila renal tubule. Genome Biol. 5, R69 (2004).
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).
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).
Manak, J.R. et al. Biological function of unannotated transcription during the early development of Drosophila melanogaster. Nat. Genet. 38, 1151–1158 (2006).
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.
The authors declare no competing financial interests.
Genes that are expressed in a single tissue in adult Drosophila. (PDF 41 kb)
Genes that show invariant expression between tissues. (PDF 32 kb)
Array probe sets against unannotated regions of the genome that show significant expression. (PDF 101 kb)
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Chintapalli, V., Wang, J. & Dow, J. Using FlyAtlas to identify better Drosophila melanogaster models of human disease. Nat Genet 39, 715–720 (2007). https://doi.org/10.1038/ng2049
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