Drosophila as an Experimental Organism for Functional Genomics

Abstract

Although historically the classical model for the understanding of development, the fruit‐fly Drosophila melanogaster is valuable for study for three reasons: as an organism in its own right, as an inexpensive, genetically powerful model for human function and disease, and as a model for economically important or harmful insects, such as vectors of disease. The sophisticated genetic tools that distinguish Drosophila from other model organisms or insects allow great spatial and temporal precisions both in genetic intervention, and in the expression of genetically encoded sensors for second messengers or intracellular environmental variables. Combined with other, novel functional readouts, it is now possible to move towards an understanding of Drosophila as a metazoan organism composed of distinct and individually tractable tissues that interact and integrate to produce a functioning whole.

Key Concepts:

  • Drosophila melanogaster is a small, easily reared insect with a short lifecycle.

  • The key advantages of Drosophila are a balance between genetic power and biomedical relevance, and rapidity and low cost of generation and maintenance of mutant and transgenic stocks.

  • The genetic toolbox available for Drosophila allows precise intervention in specific, defined cells in an otherwise normal organism, opening unique opportunities for functional biology.

  • Approximately 70% of human genes have clear Drosophila homologues, allowing the modelling of many human diseases in flies.

  • Drosophila also shares approximately 70% of its genes with Anopheles gambiae, the mosquito vector of malaria.

  • Our understanding of fly development is now mature: new phenotypes are required to provide a global functional genomic understanding.

  • An exciting challenge for the future is functional biology; understanding how the different tissues and control systems interact to make a working, successful organism.

Keywords: Drosophila melanogaster; functional genomics; transgenics; physiology

Figure 1.

Gene Ontology biological process annotations for the Drosophila genome, downloaded from Panther (http://www.pantherdb.org) on 23/10/2011. Note that developmental genes are only a small fraction of the total, and that – despite a century of work – many genes remain unclassified.

Figure 2.

Papers published on ‘Drosophila melanogaster’ by decade, based on searches on 21/10/2011 of Pubmed and Thomson/iSi Web of Knowledge. Note not just the massive volume of published output, but the small fraction indexed in Pubmed.

Figure 3.

The role of reverse genetics in functional genomics. After Dow and Davies .

Figure 4.

Published output on different Drosophila tissues or subjects. Search was performed on Thomson/iSi Web of Knowledge on 25/10/2011, using topic search for ‘Drosophila 〈tissue〉 not development’ with each tissue searched in turn; and contrasted with a search for ‘Drosophila development*’.

Figure 5.

Drosophila and mouse eye specification are surprisingly similar. (a) Eyes absent mutant of Drosophila, showing complete lack of eye formation. (b) Complete rescue of eyes absent phenotype by mouse eyes absent 2 transgene. (c) Electron micrograph of eye, showing normal ommatidial formation in rescued eye. From Bonini et al. , reproduced with permission of the Company of Biologists.

Figure 6.

Comparison of typical estimated costs and lead‐times for Drosophila and mouse transgenic models.

Figure 7.

Typical entry points and workflow for reverse‐genetic workup of genes of interest. URLs (as at 23/10/11) for the resources mentioned are as follows: FlyAtlas (post‐embryonic expression data in major tissues): flyatlas.org; FlyBase (official Drosophila database): flybase.org; FlyMine (multiorganism query engine): www.flymine.org; Pubmed (Biomedical literature from NCBI): http://www.ncbi.nlm.nih.gov/pubmed/; WoK (Biological literature from Thomson iSi): http://wokinfo.com/; Bloomington (stock centre): http://flystocks.bio.indiana.edu/; VDRC Vienna (RNAi stock centre): http://stockcenter.vdrc.at/control/main; DGRC/Nigfly Japan (stock centre): http://www.dgrc.kit.ac.jp/en/; Exelixis at Harvard (stock centre): https://Drosophila.med.harvard.edu/; DGRC (clones and vectors): https://dgrc.cgb.indiana.edu/vectors/; Injection services – examples include: Bestgene (http://www.thebestgene.com/); Duke University (http://www.biology.duke.edu/model‐system); Genetic services (http://www.geneticservices.com).

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Further Reading

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Dow, Julian AT(Mar 2012) Drosophila as an Experimental Organism for Functional Genomics. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000561]