Abstract
Nowadays, genome editing tools are indispensable for studying gene function in order to increase our knowledge of biochemical processes and disease mechanisms. The extensive availability of mutagenesis and transgenesis tools make Drosophila melanogaster an excellent model organism for geneticists. Early mutagenesis tools relied on chemical or physical methods, ethyl methane sulfonate (EMS) and X-rays respectively, to randomly alter DNA at a nucleotide or chromosomal level. Since the discovery of transposable elements and the availability of the complete fly genome, specific genome editing tools, such as P-elements, zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs), have undergone rapid development. Currently, one of the leading and most effective contemporary tools is the CRISPR-cas9 system made popular because of its low cost, effectiveness, specificity and simplicity of use. This review briefly addresses the most commonly used mutagenesis and transgenesis tools in Drosophila, followed by an in-depth review of the multipurpose CRISPR-Cas9 system and its current applications.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Adams, M.D., Celniker, S.E., Holt, R.A., Evans, C.A., Gocayne, J.D., Amanatides, P.G., Scherer, S.E., Li, P.W., Hoskins, R.A., Galle, R.F., George, R.A., Lewis, S.E., Richards, S., Ashburner, M., Henderson, S.N., Sutton, G.G., Wortman, J.R., Yandell, M.D., Zhang, Q., Chen, L.X., Brandon, R.C., Rogers, Y.H., Blazej, R.G., Champe, M., Pfeiffer, B.D., Wan, K.H., Doyle, C., Baxter, E.G., Helt, G., Nelson, C.R., Gabor, G.L., Abril, J.F., Agbayani, A., An, H.J., Andrews-Pfannkoch, C., Baldwin, D., Ballew, R.M., Basu, A., Baxendale, J., Bayraktaroglu, L., Beasley, E.M., Beeson, K.Y., Benos, P.V., Berman, B.P., Bhandari, D., Bolshakov, S., Borkova, D., Botchan, M.R., Bouck, J., Brokstein, P., Brottier, P., Burtis, K.C., Busam, D.A., Butler, H., Cadieu, E., Center, A., Chandra, I., Cherry, J.M., Cawley, S., Dahlke, C., Davenport, L.B., Davies, P., de, P.B., Delcher, A., Deng, Z., Mays, A.D., Dew, I., Dietz, S.M., Dodson, K., Doup, L.E., Downes, M., Dugan-Rocha, S., Dunkov, B.C., Dunn, P., Durbin, K.J., Evangelista, C.C., Ferraz, C., Ferriera, S., Fleischmann, W., Fosler, C., Gabrielian, A.E., Garg, N.S., Gelbart, W.M., Glasser, K., Glodek, A., Gong, F., Gorrell, J.H., Gu, Z., Guan, P., Harris, M., Harris, N.L., Harvey, D., Heiman, T.J., Hernandez, J.R., Houck, J., Hostin, D., Houston, K.A., Howland, T.J., Wei, M.H., Ibegwam, C., Jalali, M., Kalush, F., Karpen, G.H., Ke, Z., Kennison, J.A., Ketchum, K.A., Kimmel, B.E., Kodira, C.D., Kraft, C., Kravitz, S., Kulp, D., Lai, Z., Lasko, P., Lei, Y., Levitsky, A.A., Li, J., Li, Z., Liang, Y., Lin, X., Liu, X., Mattei, B., McIntosh, T.C., McLeod, M.P., McPherson, D., Merkulov, G., Milshina, N.V., Mobarry, C., Morris, J., Moshrefi, A., Mount, S.M., Moy, M., Murphy, B., Murphy, L., Muzny, D.M., Nelson, D.L., Nelson, D.R., Nelson, K.A., Nixon, K., Nusskern, D.R., Pacleb, J.M., Palazzolo, M., Pittman, G.S., Pan, S., Pollard, J., Puri, V., Reese, M.G., Reinert, K., Remington, K., Saunders, R.D., Scheeler, F., Shen, H., Shue, B.C., Siden-Kiamos, I., Simpson, M., Skupski, M.P., Smith, T., Spier, E., Spradling, A.C., Stapleton, M., Strong, R., Sun, E., Svirskas, R., Tector, C., Turner, R., Venter, E., Wang, A.H., Wang, X., Wang, Z.Y., Wassarman, D.A., Weinstock, G.M., Weissenbach, J., Williams, S.M., Woodage, T., Worley, K.C., Wu, D., Yang, S., Yao, Q.A., Ye, J., Yeh, R.F., Zaveri, J.S., Zhan, M., Zhang, G., Zhao, Q., Zheng, L., Zheng, X.H., Zhong, F.N., Zhong, W., Zhou, X., Zhu, S., Zhu, X., Smith, H.O., Gibbs, R.A., Myers, E.W., Rubin, G.M., and Venter, J.C. (2000). The genome sequence of Drosophila melanogaster. Science 287, 2185–2195.
Anders, C., Niewoehner, O., Duerst, A., and Jinek, M. (2014). Structural basis of PAM-dependent target DNA recognition by the Cas9 endonuclease. Nature 513, 569–573.
Antosh, M., Fox, D., Hasselbacher, T., Lanou, R., Neretti, N., and Cooper, L.N. (2014). Drosophila Melanogaster show a threshold effect in response to radiation. Dose Response 12, dose-response.1.
Ashburner, M. (1989). Drosophila: A Laboratory Handbook. (New York: Cold Spring Harbor Laboratory Press).
Bökel, C. (2008). EMS screens: from mutagenesis to screening and mapping. Drosophila: Methods and Protocols, 119–138.
Barrangou, R., Fremaux, C., Deveau, H., Richards, M., Boyaval, P., Moineau, S., Romero, D.A., and Horvath, P. (2007). CRISPR provides acquired resistance against viruses in prokaryotes. Science 315, 1709–1712.
Bassett, A.R., Tibbit, C., Ponting, C.P., and Liu, J.L. (2013). Highly efficient targeted mutagenesis of Drosophila with the CRISPR/Cas9 system. Cell Rep 4, 220–228.
Bellen, H.J., Levis, R.W., He, Y., Carlson, J.W., Evans-Holm, M., Bae, E., Kim, J., Metaxakis, A., Savakis, C., Schulze, K.L., Hoskins, R.A., and Spradling, A.C. (2011). The Drosophila gene disruption project: progress using transposons with distinctive site specificities. Genets 188, 731–743.
Berger, J., Suzuki, T., Senti, K.A., Stubbs, J., Schaffner, G., and Dickson, B.J. (2001). Genetic mapping with SNP markers in Drosophila. Nat Genet 29, 475–481.
Berghammer, A.J., Klingler, M., and A.~Wimmer, E. (1999). Genetic techniques: a universal marker for transgenic insects. Nature 402, 370–371.
Beumer, K.J., Trautman, J.K., Bozas, A., Liu, J.L., Rutter, J., Gall, J.G., and Carroll, D. (2008). Efficient gene targeting in Drosophila by direct embryo injection with zinc-finger nucleases. Proc Natl Acad Sci USA 105, 19821–19826.
Beumer, K.J., Trautman, J.K., Christian, M., Dahlem, T.J., Lake, C.M., Hawley, R.S., Grunwald, D.J., Voytas, D.F., and Carroll, D. (2013). Comparing zinc finger nucleases and transcription activator-like effector nucleases for gene targeting in Drosophila. G3 3, 1717–1725.
Bhakta, M.S., Henry, I.M., Ousterout, D.G., Das, K.T., Lockwood, S.H., Meckler, J.F., Wallen, M.C., Zykovich, A., Yu, Y., Leo, H., Xu, L., Gersbach, C.A., and Segal, D.J. (2013). Highly active zinc-finger nucleases by extended modular assembly. Genome Res 23, 530–538.
Bibikova, M., Beumer, K., Trautman, J.K., and Carroll, D. (2003). Enhancing gene targeting with designed zinc finger nucleases. Science 300, 764–764.
Bibikova, M., Golic, M., Golic, K.G., and Carroll, D. (2002). Targeted chromosomal cleavage and mutagenesis in Drosophila using zinc-finger nucleases. Genetics 161, 1169–1175.
Bitinaite, J., Wah, D.A., Aggarwal, A.K., and Schildkraut, I. (1998). Fok I dimerization is required for DNA cleavage. Proc Natl Acad Sci USA 95, 10570–10575.
Boch, J., and Bonas, U. (2010). Xanthomonas AvrBs3 family-type III effectors: discovery and function. Annu Rev Phytopathol 48, 419–436.
Boch, J., Scholze, H., Schornack, S., Landgraf, A., Hahn, S., Kay, S., Lahaye, T., Nickstadt, A., and Bonas, U. (2009). Breaking the code of DNA binding specificity of TAL-type III effectors. Science 326, 1509–1512.
Bolotin, A., Quinquis, B., Sorokin, A., and Ehrlich, S.D. (2005). Clustered regularly interspaced short palindrome repeats (CRISPRs) have spacers of extrachromosomal origin. Microbiology 151, 2551–2561.
Böttcher, R., Hollmann, M., Merk, K., Nitschko, V., Obermaier, C., Philippou-Massier, J., Wieland, I., Gaul, U., and Förstemann, K. (2014). Efficient chromosomal gene modification with CRISPR/cas9 and PCR-based homologous recombination donors in cultured Drosophila cells. Nucleic Acids Res 42, e89–e89.
Brand, A.H., and Dormand, E.L. (1995). The GAL4 system as a tool for unravelling the mysteries of the Drosophila nervous system. Curr Opin Neurobiol 5, 572–578.
Brouns, S.J.J., Jore, M.M., Lundgren, M., Westra, E.R., Slijkhuis, R.J.H., Snijders, A.P.L., Dickman, M.J., Makarova, K.S., Koonin, E.V., and van der Oost, J. (2008). Small CRISPR RNAs guide antiviral defense in prokaryotes. Science 321, 960–964.
Capecchi, M.R. (2005). Essay: gene targeting in mice: functional analysis of the mammalian genome for the twenty-first century. Nat Rev Genet 6, 507–512.
Chavez, A., Scheiman, J., Vora, S., Pruitt, B.W., Tuttle, M., P R Iyer, E., Lin, S., Kiani, S., Guzman, C.D., Wiegand, D.J., Ter-Ovanesyan, D., Braff, J.L., Davidsohn, N., Housden, B.E., Perrimon, N., Weiss, R., Aach, J., Collins, J.J., and Church, G.M. (2015). Highly efficient Cas9-mediated transcriptional programming. Nat Meth 12, 326–328.
Chen, K., and Gao, C. (2013). TALENs: customizable molecular DNA scissors for genome engineering of plants. J Genet Genomics 40, 271–279.
Chen, Y., Wang, Z., Ni, H., Xu, Y., Chen, Q., and Jiang, L. (2017). CRISPR/Cas9-mediated base-editing system efficiently generates gain-of-function mutations in Arabidopsis. Sci China Life Sci in press doi: 10.1007/s11427-017-9021-5.
Choi, C.M., Vilain, S., Langen, M., Van Kelst, S., De Geest, N., Yan, J., Verstreken, P., and Hassan, B.A. (2009). Conditional mutagenesis in Drosophila. Science 324, 54–54.
Chylinski, K., Makarova, K.S., Charpentier, E., and Koonin, E.V. (2014). Classification and evolution of type II CRISPR-Cas systems. Nucleic Acids Res 42, 6091–6105.
Cong, L., Ran, F.A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P.D., Wu, X., Jiang, W., Marraffini, L.A., and Zhang, F. (2013). Multiplex genome engineering using CRISPR/Cas systems. Science 339, 819–823.
Cooley, L., Berg, C., and Spradling, A. (1988). Controlling P element insertional mutagenesis. Trends Genets 4, 254–258.
Dahlem, T.J., Hoshijima, K., Jurynec, M.J., Gunther, D., Starker, C.G., Locke, A.S., Weis, A.M., Voytas, D.F., and Grunwald, D.J. (2012). Simple methods for generating and detecting locus-specific mutations induced with TALENs in the zebrafish genome. PLoS Genet 8, e1002861.
Dever, D.P., Bak, R.O., Reinisch, A., Camarena, J., Washington, G., Nicolas, C.E., Pavel-Dinu, M., Saxena, N., Wilkens, A.B., Mantri, S., Uchida, N., Hendel, A., Narla, A., Majeti, R., Weinberg, K.I., and Porteus, M.H. (2016). CRISPR/Cas9 β-globin gene targeting in human haematopoietic stem cells. Nature 539, 384–389.
Dodson, M.W., Leung, L.K., Lone, M., Lizzio, M.A., and Guo, M. (2014). Novel ethyl methanesulfonate (EMS)-induced null alleles of the Drosophila homolog of LRRK2 reveal a crucial role in endolysosomal functions and autophagy in vivo. Dis Model Mech 7, 1351–1363.
Doyon, Y., Vo, T.D., Mendel, M.C., Greenberg, S.G., Wang, J., Xia, D.F., Miller, J.C., Urnov, F.D., Gregory, P.D., and Holmes, M.C. (2011). Enhancing zinc-finger-nuclease activity with improved obligate heterodimeric architectures. Nat Meth 8, 74–79.
Eeken, J., Dejong, A., Loos, M., Vreeken, C., Romeyn, R., Pastink, A., and Lohman, P. (1994). The nature of X-ray-induced mutations in mature sperm and spermatogonial cells of Drosophila melanogaster. Mutat Res 307, 201–212.
Engels, W.R. (1992). The origin of P elements in Drosophila melanogaster. Bioessays 14, 681–686.
Engels, W.R. (1996). P elements in Drosophila. Curr Top Microbiol Immunol 204, 103–123.
Fonfara, I., Le Rhun, A., Chylinski, K., Makarova, K.S., Lécrivain, A.L., Bzdrenga, J., Koonin, E.V., and Charpentier, E. (2014). Phylogeny of Cas9 determines functional exchangeability of dual-RNA and Cas9 among orthologous type II CRISPR-Cas systems. Nucleic Acids Res 42, 2577–2590.
Friedland, A.E., Tzur, Y.B., Esvelt, K.M., Colaiácovo, M.P., Church, G.M., and Calarco, J.A. (2013). Heritable genome editing in C. elegans via a CRISPR-Cas9 system. Nat Meth 10, 741–743.
Gasiunas, G., Barrangou, R., Horvath, P., and Siksnys, V. (2012). Cas9-cr-RNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria. Proc Natl Acad Sci USA 109, E2579–E2586.
Gebler, C., Lohoff, T., Paszkowski-Rogacz, M., Mircetic, J., Chakraborty, D., Camgoz, A., Hamann, M.V., Theis, M., Thiede, C., and Buchholz, F. (2017). Inactivation of cancer mutations utilizing CRISPR/Cas9. J Natl Cancer Inst 109, djw183.
Gloor, G.B., Nassif, N.A., Johnson-Schlitz, D.M., Preston, C.R., and Engels, W.R. (1991). Targeted gene replacement in Drosophila via P elementinduced gap repair. Science 253, 1110–1117.
Gokcezade, J., Sienski, G., and Duchek, P. (2014). Efficient CRISPR/Cas9 plasmids for rapid and versatile genome editing in Drosophila. G3 4, 2279–2282.
Golic, K.G. (1991). Site-specific recombination between homologous chromosomes in Drosophila. Science 252, 958–961.
Golic, K.G., and Lindquist, S. (1989). The FLP recombinase of yeast catalyzes site-specific recombination in the Drosophila genome. Cell 59, 499–509.
Golic, M.M., Rong, Y.S., Petersen, R.B., Lindquist, S.L., and Golic, K.G. (1997). FLP-mediated DNA mobilization to specific target sites in Drosophila chromosomes. Nucleic Acids Res 25, 3665–3671.
Gorski, M.M., Eeken, J.C., de Jong, A.W., Klink, I., Loos, M., Romeijn, R.J., van Veen, B.L., Mullenders, L.H., Ferro, W., and Pastink, A. (2003). The Drosophila melanogaster DNA Ligase IV gene plays a crucial role in the repair of radiation-induced DNA double-strand breaks and acts synergistically with Rad54. Genetics 165, 1929–1941.
Gratz, S.J., Cummings, A.M., Nguyen, J.N., Hamm, D.C., Donohue, L.K., Harrison, M.M., Wildonger, J., and O’Connor-Giles, K.M. (2013). Genome engineering of Drosophila with the CRISPR RNA-guided Cas9 nuclease. Genets 194, 1029–1035.
Gratz, S.J., Ukken, F.P., Rubinstein, C.D., Thiede, G., Donohue, L.K., Cummings, A.M., and O’Connor-Giles, K.M. (2014). Highly specific and efficient CRISPR/Cas9-catalyzed homology-directed repair in Drosophila. Genets 196, 961–971.
Gray, Y.H., Tanaka, M.M., and Sved, J.A. (1996). P-element-induced recombination in Drosophila melanogaster: hybrid element insertion. Genetics 144, 1601–1610.
Greenspan, R.J. (2004). Fly Pushing: the Theory and Practice of Drosophila Genetics. (New York: Cold Spring Harbor Laboratory Press).
Gupta, A., Christensen, R.G., Rayla, A.L., Lakshmanan, A., Stormo, G.D., and Wolfe, S.A. (2012). An optimized two-finger archive for ZFN-mediated gene targeting. Nat Meth 9, 588–590.
Hacker, U., Nystedt, S., Barmchi, M.P., Horn, C., and Wimmer, E.A. (2003). piggyBac-based insertional mutagenesis in the presence of stably integrated P elements in Drosophila. Proc Natl Acad Sci USA 100, 7720–7725.
Hammond, A., Galizi, R., Kyrou, K., Simoni, A., Siniscalchi, C., Katsanos, D., Gribble, M., Baker, D., Marois, E., Russell, S., Burt, A., Windbichler, N., Crisanti, A., and Nolan, T. (2016). A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae. Nat Biotechnol 34, 78–83.
Heigwer, F., Kerr, G., and Boutros, M. (2014). E-CRISP: fast CRISPR target site identification. Nat Meth 11, 122–123.
Horn, C., and Wimmer, E.A. (2000). A versatile vector set for animal transgenesis. Dev Genes Evol 210, 630–637.
Hruscha, A., Krawitz, P., Rechenberg, A., Heinrich, V., Hecht, J., Haass, C., and Schmid, B. (2013). Efficient CRISPR/Cas9 genome editing with low off-target effects in zebrafish. Development 140, 4982–4987.
Hsu, P.D., Scott, D.A., Weinstein, J.A., Ran, F.A., Konermann, S., Agarwala, V., Li, Y., Fine, E.J., Wu, X., Shalem, O., Cradick, T.J., Marraffini, L.A., Bao, G., and Zhang, F. (2013). DNA targeting specificity of RNA-guided Cas9 nucleases. Nat Biotechnol 31, 827–832.
Ishino, Y., Shinagawa, H., Makino, K., Amemura, M., and Nakata, A. (1987). Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product. J Bacteriol 169, 5429–5433.
Jansen, R., Embden, J.D.A., Gaastra, W., and Schouls, L.M. (2002). Identification of genes that are associated with DNA repeats in prokaryotes. Mol Microbiol 43, 1565–1575.
Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J.A., and Charpentier, E. (2012). A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337, 816–821.
Jinek, M., Jiang, F., Taylor, D.W., Sternberg, S.H., Kaya, E., Ma, E., Anders, C., Hauer, M., Zhou, K., Lin, S., Kaplan, M., Iavarone, A.T., Charpentier, E., Nogales, E., and Doudna, J.A. (2014). Structures of Cas9 endonucleases reveal RNA-mediated conformational activation. Science 343, 1247997–1247997.
Josephs, E.A., Kocak, D.D., Fitzgibbon, C.J., McMenemy, J., Gersbach, C.A., and Marszalek, P.E. (2015). Structure and specificity of the RNAguided endonuclease Cas9 during DNA interrogation, target binding and cleavage. Nucleic Acids Res 43, 8924–8941.
Kaminski, R., Chen, Y., Salkind, J., Bella, R., Young, W.B., Ferrante, P., Karn, J., Malcolm, T., Hu, W., and Khalili, K. (2016). Negative feedback regulation of HIV-1 by gene editing strategy. Sci Rep 6, 31527.
Katsuyama, T., Akmammedov, A., Seimiya, M., Hess, S.C., Sievers, C., and Paro, R. (2013). An efficient strategy for TALEN-mediated genome engineering in Drosophila. Nucleic Acids Res 41, e163–e163.
Kim, Y.G., Cha, J., and Chandrasegaran, S. (1996). Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain. Proc Natl Acad Sci USA 93, 1156–1160.
Kleinstiver, B.P., Prew, M.S., Tsai, S.Q., Nguyen, N.T., Topkar, V.V., Zheng, Z., and Joung, J.K. (2015a). Broadening the targeting range of Staphylococcus aureus CRISPR-Cas9 by modifying PAM recognition. Nat Biotechnol 33, 1293–1298.
Kleinstiver, B.P., Prew, M.S., Tsai, S.Q., Topkar, V.V., Nguyen, N.T., Zheng, Z., Gonzales, A.P.W., Li, Z., Peterson, R.T., Yeh, J.R.J., Aryee, M.J., and Joung, J.K. (2015b). Engineered CRISPR-Cas9 nucleases with altered PAM specificities. Nature 523, 481–485.
Koana, T., Okada, M.O., Ogura, K., Tsujimura, H., and Sakai, K. (2007). Reduction of background mutations by low-dose X irradiation of Drosophila spermatocytes at a low dose rate. Radiat Res 167, 217–221.
Kondo, S., and Ueda, R. (2013). Highly improved gene targeting by germline-specific Cas9 expression in Drosophila. Genets 195, 715–721.
Konermann, S., Brigham, M.D., Trevino, A.E., Joung, J., Abudayyeh, O.O., Barcena, C., Hsu, P.D., Habib, N., Gootenberg, J.S., Nishimasu, H., Nureki, O., and Zhang, F. (2015). Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex. Nature 517, 583–588.
Lewis, E., and Bacher, F. (1968). Method of feeding ethyl methane sulfonate (EMS) to Drosophila males. Dros Inf Serv 43, 193.
Li, L., Wu, L.P., and Chandrasegaran, S. (1992). Functional domains in Fok I restriction endonuclease. Proc Natl Acad Sci USA 89, 4275–4279.
Lieber, M.R., Ma, Y., Pannicke, U., and Schwarz, K. (2003). Mechanism and regulation of human non-homologous DNA end-joining. Nat Rev Mol Cell Biol 4, 712–720.
Lin, S., Ewen-Campen, B., Ni, X., Housden, B.E., and Perrimon, N. (2015). In vivo transcriptional activation using CRISPR/Cas9 in Drosophila. Genets 201, 433–442.
Liu, J., Guo, Y., Li, C., Chen, Y., and Jiao, R. (2016). Methods for TALEN-mediated genomic manipulations in Drosophila. Methods Mol Biol 1338, 179–190.
Liu, J., Li, C., Yu, Z., Huang, P., Wu, H., Wei, C., Zhu, N., Shen, Y., Chen, Y., Zhang, B., Deng, W.M., and Jiao, R. (2012). Efficient and specific modifications of the Drosophila genome by means of an easy TALEN strategy. J Genet Genomics 39, 209–215.
Mahmoud, J., Fossett, N.G., Arbour-Reily, P., McDaniel, M., Tucker, A., Chang, S.H., Lee, W.R., and Aaron, C.S. (1991). DNA sequence analysis of X-ray inducedAdh null mutations in Drosophila melanogaster. Environ Mol Mutagen 18, 157–160.
Mali, P., Aach, J., Stranges, P.B., Esvelt, K.M., Moosburner, M., Kosuri, S., Yang, L., and Church, G.M. (2013a). CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering. Nat Biotechnol 31, 833–838.
Mali, P., Yang, L., Esvelt, K.M., Aach, J., Guell, M., DiCarlo, J.E., Norville, J.E., and Church, G.M. (2013b). RNA-guided human genome engineering via Cas9. Science 339, 823–826.
Martin, S.G., Dobi, K.C., and StJohnston, D. (2001). A rapid method to map mutations in Drosophila. Genome Biol 2, RESEARCH0036.
McClintock, B. (1950). The origin and behavior of mutable loci in maize. Proc Natl Acad Sci USA 36, 344–355.
McVey, M., Radut, D., and Sekelsky, J.J. (2004). End-joining repair of double- strand breaks in Drosophila melanogaster is largely DNA ligase IV independent. Genets 168, 2067–2076.
Metaxakis, A., Oehler, S., Klinakis, A., and Savakis, C. (2005). Minos as a genetic and genomic tool in Drosophila melanogaster. Genets 171, 571–581.
Mglinets, V.A. (1973). Cytological investigation of crossovers induced by irradiation in males of Drosophila melanogaster. Sov Genet 7, 1036–1041.
Miller, J.C., Holmes, M.C., Wang, J., Guschin, D.Y., Lee, Y.L., Rupniewski, I., Beausejour, C.M., Waite, A.J., Wang, N.S., Kim, K.A., Gregory, P.D., Pabo, C.O., and Rebar, E.J. (2007). An improved zinc-finger nuclease architecture for highly specific genome editing. Nat Biotechnol 25, 778–785.
Miller, J.C., Tan, S., Qiao, G., Barlow, K.A., Wang, J., Xia, D.F., Meng, X., Paschon, D.E., Leung, E., Hinkley, S.J., Dulay, G.P., Hua, K.L., Ankoudinova, I., Cost, G.J., Urnov, F.D., Zhang, H.S., Holmes, M.C., Zhang, L., Gregory, P.D., and Rebar, E.J. (2011). A TALE nuclease architecture for efficient genome editing. Nat Biotechnol 29, 143–148.
Mohr, S.E., and Gelbart, W.M. (2002). Using the P{wHy} hybrid transposable element to disrupt genes in region 54D-55B in Drosophila melanogaster. Genetics 162, 165–176.
Mojica, F.J.M., Díez-Villaseñor, C., García-Martínez, J., and Soria, E. (2005). Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements. J Mol Evol 60, 174–182.
Mojica, F.J.M., Diez-Villasenor, C., Soria, E., and Juez, G. (2000). Biological significance of a family of regularly spaced repeats in the genomes of Archaea, Bacteria and mitochondria. Mol Microbiol 36, 244–246.
Moscou, M.J., and Bogdanove, A.J. (2009). A simple cipher governs DNA recognition by TAL effectors. Science 326, 1501–1501.
Muller, H.J. (1927). Artificial transmutation of the gene. Science 66, 84–87.
Nairz, K., Zipperlen, P., Dearolf, C., Basler, K., and Hafen, E. (2004). A reverse genetic screen in Drosophila using a deletion-inducing mutagen. Genome Biol 5, R83.
Ni, J.Q., Zhou, R., Czech, B., Liu, L.P., Holderbaum, L., Yang-Zhou, D., Shim, H.S., Tao, R., Handler, D., Karpowicz, P., Binari, R., Booker, M., Brennecke, J., Perkins, L.A., Hannon, G.J., and Perrimon, N. (2011). A genome-scale shRNA resource for transgenic RNAi in Drosophila. Nat Meth 8, 405–407.
Nishimasu, H., Ran, F.A., Hsu, P.D., Konermann, S., Shehata, S.I., Dohmae, N., Ishitani, R., Zhang, F., and Nureki, O. (2014). Crystal structure of Cas9 in complex with guide RNA and target DNA. Cell 156, 935–949.
Patton, J.S., Gomes, X.V., and Geyer, P.K. (1992). Position-independent germline transformation in Drosophila using a cuticle pigmentation gene as a selectable marker. Nucl Acids Res 20, 5859–5860.
Pavletich, N.P., and Pabo, C.O. (1991). Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 A. Science 252, 809–817.
Peabody, D.S. (1993). The RNA binding site of bacteriophage MS2 coat protein. EMBO J 12, 595–600.
Peterson, B.A., Haak, D.C., Nishimura, M.T., Teixeira, P.J.P.L., James, S.R., Dangl, J.L., and Nimchuk, Z.L. (2016). Genome-wide assessment of efficiency and specificity in CRISPR/Cas9 mediated multiple site targeting in Arabidopsis. PLoS ONE 11, e0162169.
Pfeifer, G.P., You, Y.H., and Besaratinia, A. (2005). Mutations induced by ultraviolet light. Mutat Res 571, 19–31.
Pirrotta, V. (1988). Vectors for P-mediated transformation in Drosophila. Biotechnology 10, 437–456.
Port, F., and Bullock, S.L. (2016). Augmenting CRISPR applications in Drosophila with tRNA-flanked sgRNAs. Nat Meth 13, 852–854.
Port, F., Chen, H.M., Lee, T., and Bullock, S.L. (2014). Optimized CRISPR/Cas tools for efficient germline and somatic genome engineering in Drosophila. Proc Natl Acad Sci USA 111, E2967–E2976.
Pourcel, C., Salvignol, G., and Vergnaud, G. (2005). CRISPR elements in Yersinia pestis acquire new repeats by preferential uptake of bacteriophage DNA, and provide additional tools for evolutionary studies. Microbiology 151, 653–663.
Ren, B., Yan, F., Kuang, Y., Li, N., Zhang, D., Lin, H., and Zhou, H. (2017). A CRISPR/Cas9 toolkit for efficient targeted base editing to induce genetic variations in rice. Sci China Life Sci in press doi: 10.1007/s11427-016-0406-x.
Ren, X., Sun, J., Housden, B.E., Hu, Y., Roesel, C., Lin, S., Liu, L.P., Yang, Z., Mao, D., Sun, L., Wu, Q., Ji, J.Y., Xi, J., Mohr, S.E., Xu, J., Perrimon, N., and Ni, J.Q. (2013). Optimized gene editing technology for Drosophila melanogaster using germ line-specific Cas9. Proc Natl Acad Sci USA 110, 19012–19017.
Ren, X., Yang, Z., Mao, D., Chang, Z., Qiao, H.H., Wang, X., Sun, J., Hu, Q., Cui, Y., Liu, L.P., Ji, J.Y., Xu, J., and Ni, J.Q. (2014a). Performance of the Cas9 nickase system in Drosophila melanogaster. G3 4, 1955–1962.
Ren, X., Yang, Z., Xu, J., Sun, J., Mao, D., Hu, Y., Yang, S.J., Qiao, H.H., Wang, X., Hu, Q., Deng, P., Liu, L.P., Ji, J.Y., Li, J.B., and Ni, J.Q. (2014b). Enhanced specificity and efficiency of the CRISPR/Cas9 system with optimized sgRNA parameters in Drosophila. Cell Rep 9, 1151–1162.
Rio, D.C. (1990). Molecular mechanisms regulating Drosophila P element transposition. Annu Rev Genet 24, 543–576.
Rio, D.C., Laski, F.A., and Rubin, G.M. (1986). Identification and immunochemical analysis of biologically active Drosophila P element transposase. Cell 44, 21–32.
Roberts, D.B. (1987). Necrotizing fasciffis of the vulva. Am J Obstetr Gynecol 157, 568–571.
Robertson, H.M., Preston, C.R., Phillis, R.W., Johnson-Schlitz, D.M., Benz, W.K., and Engels, W.R. (1988). A stable genomic source of P element transposase in Drosophila melanogaster. Genetics 118, 461–470.
Rong, Y.S., and Golic, K.G. (2000). Gene targeting by homologous recombination in Drosophila. Science 288, 2013–2018.
Sander, J.D., Dahlborg, E.J., Goodwin, M.J., Cade, L., Zhang, F., Cifuentes, D., Curtin, S.J., Blackburn, J.S., Thibodeau-Beganny, S., Qi, Y., Pierick, C.J., Hoffman, E., Maeder, M.L., Khayter, C., Reyon, D., Dobbs, D., Langenau, D.M., Stupar, R.M., Giraldez, A.J., Voytas, D.F., Peterson, R.T., Yeh, J.R.J., and Joung, J.K. (2011). Selection-free zinc-finger-nuclease engineering by context-dependent assembly (CoDA). Nat Meth 8, 67–69.
Sebo, Z.L., Lee, H.B., Peng, Y., and Guo, Y. (2014). A simplified and efficient germline-specific CRISPR/Cas9 system for Drosophila genomic engineering. Fly 8, 52–57.
Sepp, K.J., and Auld, V.J. (1999). Conversion of lacZ enhancer trap lines to GAL4 lines using targeted transposition in Drosophila melanogaster. Genetics 151, 1093–1101.
Shen, L., Hua, Y., Fu, Y., Li, J., Liu, Q., Jiao, X., Xin, G., Wang, J., Wang, X., Yan, C., and Wang, K. (2017). Rapid generation of genetic diversity by multiplex CRISPR/Cas9 genome editing in rice. Sci China Life Sci 309, in press doi: 10.1007/s11427-017-9008-8.
Slaymaker, I.M., Gao, L., Zetsche, B., Scott, D.A., Yan, W.X., and Zhang, F. (2016). Rationally engineered Cas9 nucleases with improved specificity. Science 351, 84–88.
Smith, J., Bibikova, M., Whitby, F.G., Reddy, A.R., Chandrasegaran, S., and Carroll, D. (2000). Requirements for double-strand cleavage by chimeric restriction enzymes with zinc finger DNA-recognition domains. Nucleic Acids Res 28, 3361–3369.
Spradling, A.C., Bellen, H.J., and Hoskins, R.A. (2011). Drosophila P elements preferentially transpose to replication origins. Proc Natl Acad Sci USA 108, 15948–15953.
Spradling, A.C., and Rubin, G.M. (1982). Transposition of cloned P elements into Drosophila germ line chromosomes. Science 218, 341–347.
StJohnston, D. (2002). The art and design of genetic screens: Drosophila melanogaster. Nat Rev Genet 3, 176–188.
Sternberg, S.H., Redding, S., Jinek, M., Greene, E.C., and Doudna, J.A. (2014). DNA interrogation by the CRISPR RNA-guided endonuclease Cas9. Nature 507, 62–67.
Szczepek, M., Brondani, V., Büchel, J., Serrano, L., Segal, D.J., and Cathomen, T. (2007). Structure-based redesign of the dimerization interface reduces the toxicity of zinc-finger nucleases. Nat Biotechnol 25, 786–793.
Szostak, J.W., Orr-Weaver, T.L., Rothstein, R.J., and Stahl, F.W. (1983). The double-strand-break repair model for recombination. Cell 33, 25–35.
Takata, M., Sasaki, M.S., Sonoda, E., Morrison, C., Hashimoto, M., Utsumi, H., Yamaguchi-Iwai, Y., Shinohara, A., and Takeda, S. (1998). Homologous recombination and non-homologous end-joining pathways of DNA double-strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells. EMBO J 17, 5497–5508.
Vazquez, J., Belmont, A.S., and Sedat, J.W. (2002). The dynamics of homologous chromosome pairing during male Drosophila meiosis. Curr Biol 12, 1473–1483.
Venken, K.J.T., and Bellen, H.J. (2007). Transgenesis upgrades for Drosophila melanogaster. Dev 134, 3571–3584.
Wang, H., Yang, H., Shivalila, C.S., Dawlaty, M.M., Cheng, A.W., Zhang, F., and Jaenisch, R. (2013). One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell 153, 910–918.
Wen, K., Yang, L., Xiong, T., Di, C., Ma, D., Wu, M., Xue, Z., Zhang, X., Long, L., Zhang, W., Zhang, J., Bi, X., Dai, J., Zhang, Q., Lu, Z.J., and Gao, G. (2016). Critical roles of long noncoding RNAs in Drosophila spermatogenesis. Genome Res 26, 1233–1244.
Xu, J., Ren, X., Sun, J., Wang, X., Qiao, H.H., Xu, B.W., Liu, L.P., and Ni, J.Q. (2015). A toolkit of CRISPR-based genome editing systems in Drosophila. J Genet Genomics 42, 141–149.
Xue, Z., Wu, M., Wen, K., Ren, M., Long, L., Zhang, X., and Gao, G. (2014). CRISPR/Cas9 mediates efficient conditional mutagenesis in Drosophila. G3 4, 2167–2173.
Yu, Z., Chen, H., Liu, J., Zhang, H., Yan, Y., Zhu, N., Guo, Y., Yang, B., Chang, Y., Dai, F., Liang, X., Chen, Y., Shen, Y., Deng, W.M., Chen, J., Zhang, B., Li, C., and Jiao, R. (2014). Various applications of TALENand CRISPR/Cas9-mediated homologous recombination to modify the Drosophila genome. Biol Open 3, 271–280.
Yu, Z., Ren, M., Wang, Z., Zhang, B., Rong, Y.S., Jiao, R., and Gao, G. (2013). Highly efficient genome modifications mediated by CRISPR/Cas9 in Drosophila. Genets 195, 289–291.
Zhang, P., and Spradling, A.C. (1993). Efficient and dispersed local P element transposition from Drosophila females. Genetics 133, 361–373.
Acknowledgements
We thank members of the Ni lab for their critical comments on the manuscript. This work was supported by the National Key Technology Research and Development Program of the Ministry of Science and Technology of the People’s Republic of China (2015BAI09B03, 2016YFE0113700), the National Natural Science Foundation of China (31371496, 31571320), the National Basic Research Program (2013CB35102).
Author information
Authors and Affiliations
Corresponding authors
Additional information
Contributed equally to this work
Rights and permissions
About this article
Cite this article
Ren, X., Holsteens, K., Li, H. et al. Genome editing in Drosophila melanogaster: from basic genome engineering to the multipurpose CRISPR-Cas9 system. Sci. China Life Sci. 60, 476–489 (2017). https://doi.org/10.1007/s11427-017-9029-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11427-017-9029-9