Skip to main content
SpringerLink
Log in

Humanized Flies and Resources for Cross-Species Study

  • Chapter
  • First Online:
Drosophila Models for Human Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1076))

Abstract

The completion of whole-genome sequences has greatly broadened our understanding of genes and genomes. The availability of model organism databases facilitates the sharing of information. However, it is still challenging to predict the pathogenicity of missense mutations, and it is more difficult to evaluate the functional impact of noncoding variants. What is more, it is a primary question to understand what variants interact to express phenotypes. Powerful genetic tools and resources available in Drosophila now make it much easier to replace endogenous genes with exogenous DNA. This allows us to directly investigate and compare the functions of orthologs, variants, and fragments in a single genetic background, the value of which should be widely appreciated. To take one example, we are currently studying so-called ultra-conserved elements, which have been conserved over hundreds of millions of years of vertebrate evolution. Many highly conserved elements are in noncoding regions and are thought to play a pivotal role in gene regulation. We generated transgenic fly lines carrying human ultra-conserved elements for enhancer reporter assay and indeed observed the reporter expression in one or more tissues of embryos and larvae in all elements tested. Currently, transgenic human-ORF lines expressing human genes under the control of GAL4/UAS system are also been developed, which will greatly facilitate the cross-species in Drosophila. In this chapter, I introduce useful tools and resources available in Drosophila to nonspecialists, encouraging their further use in many applications.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Ahituv N, Zhu Y, Visel A, et al. Deletion of ultraconserved elements yields viable mice. PLoS Biol. 2007;5:e234.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bassett AR, Tibbit C, Ponting CP, et al. Highly efficient targeted mutagenesis of Drosophila with the CRISPR/Cas9 system. Cell Rep. 2013;4:220–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beinert N, Werner M, Dowe G, et al. Systematic gene targeting on the X chromosome of Drosophila melanogaster. Chromosoma. 2004;113:271–5.

    Article  CAS  PubMed  Google Scholar 

  • Bejerano G, Pheasant M, Makunin I, et al. Ultraconserved elements in the human genome. Science. 2004;304:1321–5.

    Article  CAS  PubMed  Google Scholar 

  • Bellen HJ, Levis RW, Liao G, et al. The BDGP gene disruption project: single transposon insertions associated with 40% of Drosophila genes. Genetics. 2004;167:761–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bence M, Jankovics J, Lukácsovich T, et al. Combining the auxin-inducible degradation system with CRISPR/Cas9-based genome editing for the conditional depletion of endogenous Drosophila melanogaster proteins. FEBS J. 2017;284:1056–69.

    Article  CAS  PubMed  Google Scholar 

  • Brand AH, Perrimon N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development. 1993;118:401–15.

    PubMed  CAS  Google Scholar 

  • Brüschweiler W, Gehring W. A method for freezing living ovaries of Drosophila melanogaster larvae and its application to the storage of mutant stocks. Experientia. 1973;29:134–5.

    Article  PubMed  Google Scholar 

  • Chao H-T, Davids M, Burke E, et al. A syndromic neurodevelopmental disorder caused by de novo variants in EBF3. Am J Hum Genet. 2017;100:128–37.

    Article  CAS  PubMed  Google Scholar 

  • Crisp J, Merriam J. Effciency of an F1 selection screen in a pilot two-component mutagenesis involving Drosophila melanogaster misexpression phenotypes. Drosoph Inf Serv. 1997;80:90–2.

    Google Scholar 

  • Dembeck LM, Huang W, Magwire MM, et al. Genetic architecture of abdominal pigmentation in Drosophila melanogaster. PLoS Genet. 2015;11:e1005163.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dietzl G, Chen D, Schnorrer F, et al. A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila. Nature (Lond). 2007;448:151–6.

    Article  CAS  Google Scholar 

  • Douzery EJP, Snell EA, Bapteste E, et al. The timing of eukaryotic evolution: does a relaxed molecular clock reconcile proteins and fossils? Proc Natl Acad Sci U S A. 2004;101:15386–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Germani F, Bergantinos C, Johnston LA. Mosaic analysis in Drosophila. Genetics. 2018;208:473–90.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ghosh S, Tibbit C, Liu J-L. Effective knockdown of Drosophila long non-coding RNAs by CRISPR interference. Nucl Acids Res. 2016;44:e84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gratz SJ, Cummings AM, Nguyen JN, et al. Genome engineering of Drosophila with the CRISPR RNA-guided Cas9 nuclease. Genetics. 2013;194:1029–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Halder G, Callaerts P, Gehring WJ. Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila. Science. 1995;267:1788–92.

    Article  CAS  PubMed  Google Scholar 

  • Hayashi S, Ito K, Sado Y, et al. GETDB, a database compiling expression patterns and molecular locations of a collection of Gal4 enhancer traps. Genesis. 2002;34:58–61.

    Article  CAS  PubMed  Google Scholar 

  • Hu Y, Comjean A, Roesel C, et al. FlyRNAi.org—the database of the Drosophila RNAi screening center and transgenic RNAi project: 2017 update. Nucl Acids Res. 2017;45:D672–8.

    Article  CAS  PubMed  Google Scholar 

  • Huang W, Carbone MA, Magwire MM, et al. Genetic basis of transcriptome diversity in Drosophila melanogaster. Proc Natl Acad Sci U S A. 2015;112:E6010–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jenett A, Rubin GM, Ngo T-TB, et al. A GAL4-driver line resource for Drosophila neurobiology. Cell Rep. 2012;2:991–1001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jordan DM, Frangakis SG, Golzio C, et al. Identification of cis-suppression of human disease mutations by comparative genomics. Nature (Lond). 2015;524:225–9.

    Article  CAS  Google Scholar 

  • Kachroo AH, Laurent JM, Yellman CM, et al. Systematic humanization of yeast genes reveals conserved functions and genetic modularity. Science. 2015;348:921–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kalderimis A, Lyne R, Butano D, et al. InterMine: extensive web services for modern biology. Nucl Acids Res. 2014;42:W468–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kanamori T, Yasuno Y, Tomaru M, et al. Reduced male fertility of the Canton-S strain due to spermiogenic failure. Drosoph Inf Ser. 2014;97:21–4.

    Google Scholar 

  • Kataoka T, Powers S, Cameron S, et al. Functional homology of mammalian and yeast RAS genes. Cell. 1985;40:19–26.

    Article  CAS  PubMed  Google Scholar 

  • Kondo S, Ueda R. Highly improved gene targeting by germline-specific Cas9 expression in Drosophila. Genetics. 2013;195:715–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kondrashov AS, Sunyaev S, Kondrashov FA. Dobzhansky–Muller incompatibilities in protein evolution. Proc Natl Acad Sci U S A. 2002;99:14878–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kong A, Frigge ML, Masson G, et al. Rate of de novo mutations and the importance of father’s age to disease risk. Nature. 2012;488:471–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kvon EZ, Kazmar T, Stampfel G, et al. Genome-scale functional characterization of Drosophila developmental enhancers in vivo. Nature. 2014;512:91–5.

    Article  CAS  PubMed  Google Scholar 

  • Lai S-L, Lee T. Genetic mosaic with dual binary transcriptional systems in Drosophila. Nat Neurosci. 2006;9:703–9.

    Article  CAS  PubMed  Google Scholar 

  • Lee T, Luo L. Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis. Neuron. 1999;22:451–61.

    Article  CAS  PubMed  Google Scholar 

  • Lee MG, Nurse P. Complementation used to clone a human homologue of the fission yeast cell cycle control gene cdc2. Nature. 1987;327:31–5.

    Article  CAS  PubMed  Google Scholar 

  • Lin S, Ewen-Campen B, Ni X, et al. In vivo transcriptional activation using CRISPR/Cas9 in Drosophila. Genetics. 2015;201:433–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lohmueller KE, Indap AR, Schmidt S, et al. Proportionally more deleterious genetic variation in European than in African populations. Nature. 2008;451:994–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luan H, Peabody NC, Vinson CR, et al. Refined spatial manipulation of neuronal function by combinatorial restriction of transgene expression. Neuron. 2006;52:425–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • MacArthur DG, Tyler-Smith C. Loss-of-function variants in the genomes of healthy humans. Hum Mol Genet. 2010;19:R125–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • MacArthur DG, Balasubramanian S, Frankish A, et al. A systematic survey of loss-of-function variants in human protein-coding genes. Science. 2012;335:823–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mackay TFC, Richards S, Stone EA, et al. The Drosophila melanogaster genetic reference panel. Nature. 2012;482:173–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Malicki J, Schughart K, McGinnis W. Mouse Hox-2.2 specifies thoracic segmental identity in Drosophila embryos and larvae. Cell. 1990;63:961–7.

    Article  CAS  PubMed  Google Scholar 

  • Maurano MT, Humbert R, Rynes E, et al. Systematic localization of common disease-associated variation in regulatory DNA. Science. 2012;337:1190–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mazur P, Cole KW, Hall JW, et al. Cryobiological preservation of Drosophila embryos. Science. 1992;258:1932–5.

    Article  CAS  PubMed  Google Scholar 

  • McGary KL, Park TJ, Woods JO, et al. Systematic discovery of nonobvious human disease models through orthologous phenotypes. Proc Natl Acad Sci U S A. 2010;107:6544–9.

    Article  PubMed  PubMed Central  Google Scholar 

  • McGinnis N, Kuziora MA, McGinnis W. Human Hox-4.2 and Drosophila Deformed encode similar regulatory specificities in Drosophila embryos and larvae. Cell. 1990;63:969–76.

    Article  CAS  PubMed  Google Scholar 

  • Musunuru K, Strong A, Frank-Kamenetsky M, et al. From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus. Nature. 2010;466:714–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nagarkar-Jaiswal S, Lee P-T, Campbell ME, et al. A library of MiMICs allows tagging of genes and reversible, spatial and temporal knockdown of proteins in Drosophila. elife. 2015;4:e05338.

    Article  PubMed Central  Google Scholar 

  • Parks AL, Cook KR, Belvin M, et al. Systematic generation of high-resolution deletion coverage of the Drosophila melanogaster genome. Nat Genet. 2004;36:288–92.

    Article  CAS  PubMed  Google Scholar 

  • Pennacchio LA, Ahituv N, Moses AM, et al. In vivo enhancer analysis of human conserved non-coding sequences. Nature. 2006;444:499–502.

    Article  CAS  PubMed  Google Scholar 

  • Pfeiffer BD, Jenett A, Hammonds AS, et al. Tools for neuroanatomy and neurogenetics in Drosophila. Proc Natl Acad Sci U S A. 2008;105:9715–20.

    Article  PubMed  PubMed Central  Google Scholar 

  • Plotnikova OV, Kondrashov FA, Vlasov PK, et al. Conversion and compensatory evolution of the γ-crystallin genes and identification of a cataractogenic mutation that reverses the sequence of the human CRYGD gene to an ancestral state. Am J Hum Genet. 2007;81:32–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Port F, Bullock SL. Augmenting CRISPR applications in Drosophila with tRNA-flanked sgRNAs. Nat Methods. 2016;13:852–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Potter CJ, Tasic B, Russler EV, et al. The Q system: a repressible binary system for transgene expression, lineage tracing, and mosaic analysis. Cell. 2010;141:536–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rahbari R, Wuster A, Lindsay SJ, et al. Timing, rates and spectra of human germline mutation. Nat Genet. 2016;48:126–33.

    Article  CAS  PubMed  Google Scholar 

  • Rheinbay E, Parasuraman P, Grimsby J, et al. Recurrent and functional regulatory mutations in breast cancer. Nature. 2017;547:55–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rørth P. A modular misexpression screen in Drosophila detecting tissue-specific phenotypes. Proc Natl Acad Sci U S A. 1996;93:12418–22.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ryder E, Blows F, Ashburner M, et al. The DrosDel collection: a set of P-element insertions for generating custom chromosomal aberrations in Drosophila melanogaster. Genetics. 2004;167:797–813.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shorter J, Couch C, Huang W, et al. Genetic architecture of natural variation in Drosophila melanogaster aggressive behavior. Proc Natl Acad Sci U S A. 2015;112:E3555–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith RN, Aleksic J, Butano D, et al. InterMine: a flexible data warehouse system for the integration and analysis of heterogeneous biological data. Bioinformatics. 2012;28:3163–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Staudt N, Molitor A, Somogyi K, et al. Gain-of-function screen for genes that affect Drosophila muscle pattern formation. PLoS Genet. 2005;1:e55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Steponkus PL, Myers SP, Lynch DV, et al. Cryopreservation of Drosophila melanogaster embryos. Nature. 1990;345:170–2.

    Article  CAS  PubMed  Google Scholar 

  • Tennessen JA, Bigham AW, O’Connor TD, et al. Evolution and functional impact of rare coding variation from deep sequencing of human exomes. Science. 2012;337:64–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • The 1000 Genomes Project Consortium. An integrated map of genetic variation from 1,092 human genomes. Nature. 2012;491:56–65.

    Article  CAS  PubMed Central  Google Scholar 

  • The Chimpanzee Sequencing and Analysis Consortium. Initial sequence of the chimpanzee genome and comparison with the human genome. Nature. 2005;437:69–87.

    Article  CAS  Google Scholar 

  • The ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489:57–74.

    Article  CAS  PubMed Central  Google Scholar 

  • Thibault ST, Singer MA, Miyazaki WY, et al. A complementary transposon tool kit for Drosophila melanogaster using P and piggyBac. Nat Genet. 2004;36:283–7.

    Article  CAS  PubMed  Google Scholar 

  • Toba G, Ohsako T, Miyata N. The gene search system: a method for efficient detection and rapid molecular identification of genes in Drosophila melanogaster. Genetics. 1999;151:725–37.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Venken KJT, Schulze KL, Haelterman NA, et al. MiMIC: a highly versatile transposon insertion resource for engineering Drosophila melanogaster genes. Nat Methods. 2011;8:737–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Visel A, Prabhakar S, Akiyama JA, et al. Ultraconservation identifies a small subset of extremely constrained developmental enhancers. Nat Genet. 2008;40:58–160.

    Article  CAS  Google Scholar 

  • Vogelstein B, Papadopoulos N, Velculescu VE, et al. Cancer genome landscapes. Science. 2013;339:1546–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang VY, Hassan BA, Bellen HJ, et al. Drosophila atonal fully rescues the phenotype of math1 null mice: new functions evolve in new cellular contexts. Curr Biol. 2002;12:1611–6.

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Al-Ouran R, Hu Y, et al. MARRVEL: integration of human and model organism genetic resources to facilitate functional annotation of the human genome. Am J Hum Genet. 2017;100:843–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wangler MF, Yamamoto S, Chao H-T, et al. Model organisms facilitate rare disease diagnosis and therapeutic research. Genetics. 2017;207:9–27.

    Article  PubMed  PubMed Central  Google Scholar 

  • Woods JO, Singh-Blom UM, Laurent JM, et al. Prediction of gene-phenotype associations in humans, mice, and plants using phenologs. BMC Bioinf. 2013;14:203.

    Article  Google Scholar 

  • Yamamoto S, Jaiswal M, Charng W-L, et al. A Drosophila genetic resource of mutants to study mechanisms underlying human genetic diseases. Cell. 2014;159:200–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yoon WH, Sandoval H, Nagarkar-Jaiswal S, et al. Loss of Nardilysin, a mitochondrial co-chaperone for α-ketoglutarate dehydrogenase, promotes mTORC1 activation and neurodegeneration. Neuron. 2017;93:115–31.

    Article  CAS  PubMed  Google Scholar 

  • Yu Z, Ren M, Wang Z, et al. Highly efficient genome modifications mediated by CRISPR/Cas9 in Drosophila. Genetics. 2013;195:289–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Drosophila Genomics and Genetic Resources, Advanced Insect Research Promotion Center, Kyoto Institute of Technology, Kyoto, Japan

    Toshiyuki Takano-Shimizu-Kouno

  2. Advanced Technology Center, Kyoto Institute of Technology, Kyoto, Japan

    Takashi Ohsako

Authors
  1. Toshiyuki Takano-Shimizu-Kouno
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takashi Ohsako
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Toshiyuki Takano-Shimizu-Kouno .

Editor information

Editors and Affiliations

  1. Department of Applied Biology, Kyoto Institute of Technology, Kyoto, Japan

    Masamitsu Yamaguchi

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Takano-Shimizu-Kouno, T., Ohsako, T. (2018). Humanized Flies and Resources for Cross-Species Study. In: Yamaguchi, M. (eds) Drosophila Models for Human Diseases. Advances in Experimental Medicine and Biology, vol 1076. Springer, Singapore. https://doi.org/10.1007/978-981-13-0529-0_15

Download citation

Publish with us

Policies and ethics

Search

Navigation