BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

Functional Genomic Approaches Using the Nematode Caenorhabditis elegans as a Model System

  • Lee, Jun-Ho (National Research Laboratory, Department of Biology, Yonsei University) ;
  • Nam, Seung-Hee (National Research Laboratory, Department of Biology, Yonsei University) ;
  • Hwang, Soon-Baek (National Research Laboratory, Department of Biology, Yonsei University) ;
  • Hong, Min-Gi (National Research Laboratory, Department of Biology, Yonsei University) ;
  • Kwon, Jae-Young (National Research Laboratory, Department of Biology, Yonsei University) ;
  • Joeng, Kyu-Sang (National Research Laboratory, Department of Biology, Yonsei University) ;
  • Im, Seol-Hee (National Research Laboratory, Department of Biology, Yonsei University) ;
  • Shim, Ji-Won (National Research Laboratory, Department of Biology, Yonsei University) ;
  • Park, Moon-Cheol (National Research Laboratory, Department of Biology, Yonsei University)
  • Published : 2004.01.31
Download PDF
⟨ Previous Next ⟩

Abstract

Since the completion of the genome project of the nematode C. elegans in 1998, functional genomic approaches have been applied to elucidate the gene and protein networks in this model organism. The recent completion of the whole genome of C. briggsae, a close sister species of C. elegans, now makes it possible to employ the comparative genomic approaches for identifying regulatory mechanisms that are conserved in these species and to make more precise annotation of the predicted genes. RNA interference (RNAi) screenings in C. elegans have been performed to screen the whole genome for the genes whose mutations give rise to specific phenotypes of interest. RNAi screens can also be used to identify genes that act genetically together with a gene of interest. Microarray experiments have been very useful in identifying genes that exhibit co-regulated expression profiles in given genetic or environmental conditions. Proteomic approaches also can be applied to the nematode, just as in other species whose genomes are known. With all these functional genomic tools, genetics will still remain an important tool for gene function studies in the post genome era. New breakthroughs in C. elegans biology, such as establishing a feasible gene knockout method, immortalized cell lines, or identifying viruses that can be used as vectors for introducing exogenous gene constructs into the worms, will augment the usage of this small organism for genome-wide biology.

Keywords

References

  1. Ashrafi, K., Chang, F. Y., Watts, J. L., Fraser, A. G., Kamath, R. S., Ahringer, J. and Ruvkun, G. (2003) Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes. Nature 421, 268-272. https://doi.org/10.1038/nature01279
  2. Bailey, T. L. and Elkan, C. (1995) The value of prior knowledge in discovering motifs with MEME. Proc. Int. Conf. Intell. Syst. Mol. Biol. 3, 21-29.
  3. Blumenthal, T., Evans, D., Link, C. D., Guffanti, A., Lawson, D., Thierry-Mieg, J., Thierry-Mieg, D., Chiu, W. L., Duke, K., Kiraly, M. and Kim, S. K. (2002) A global analysis of Caenorhabditis elegans operons. Nature 417, 851-854. https://doi.org/10.1038/nature00831
  4. Brenner, S. (1974) The genetics of Caenorhabditis elegans. Genetics 77, 71-94.
  5. Choi, B. K., Chitwood, D. J. and Paik, Y. K. (2003) Proteomic changes during disturbance of cholesterol metabolism by Azacoprostane treatment in Caenorhabditis elegans. Mol. Cell Proteomics 2, 1086-1095. https://doi.org/10.1074/mcp.M300036-MCP200
  6. Cui, M. and Han, M. (2003) Cis regulatory requirements for vulval cell-specific expression of the Caenorhabditis elegans fibroblast growth factor gene egl-17. Dev. Biol. 257, 104-116. https://doi.org/10.1016/S0012-1606(03)00033-2
  7. Fire, A., Xu, S., Montgomery, M. K., Kostas, S. A., Driver, S. E. and Mello, C. C. (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 391, 806-811. https://doi.org/10.1038/35888
  8. Fraser, A. G., Kamath, R. S., Zipperlen, P., Martinez-Campos, M., Sohrmann, M. and Ahringer, J. (2000) Functional genomic analysis of C. elegans chromosome I by systematic RNA interference. Nature 408, 325-330. https://doi.org/10.1038/35042517
  9. Gonczy, P., Echeverri, G., Oegema, K., Coulson, A., Jones, S. J., Copley, R. R., Duperon, J., Oegema, J., Brehm, M., Cassin, E. et al. (2000) Functional genomic analysis of cell division in C. elegans using RNAi of genes on chromosome III. Nature 408, 331-336. https://doi.org/10.1038/35042526
  10. GuhaThakurta, D., Palomar, L., Stormo, G. D., Tedesco, P., Johnson, T. E., Walker, D. W., Lithgow, G., Kim, S. and Link, C. D. (2002) Identification of a novel cis-regulatory element involved in the heat shock response in Caenorhabditis elegans using microarray gene expression and computational methods. Genome Res. 12, 701-712. https://doi.org/10.1101/gr.228902
  11. Heschl, M. F. and Baillie, D. L. (1990) Functional elements and domains inferred from sequence comparisons of a heat shock gene in two nematodes. J. Mol. Evol. 31, 3-9. https://doi.org/10.1007/BF02101786
  12. Hill, A. A., Hunter, C. P., Tsung, B. T., Tucker-Kellogg, G. and Brown, E. L. (2000) Genomic analysis of gene expression in C. elegans. Science 290, 809-812. https://doi.org/10.1126/science.290.5492.809
  13. Hirabayashi, J., Hayama, K., Kaji, H., Isobe, T. and Kasai, K. (2002) Affinity capturing and gene assignment of soluble glycoproteins produced by the nematode Caenorhabditis elegans. J. Biochem. (Tokyo) 132, 103-114. https://doi.org/10.1093/oxfordjournals.jbchem.a003186
  14. Hwang, S. B. and Lee, J. (2003) Neuron cell type-specific SNAP-25 expression driven by multiple regulatory elements in the nematode Caenorhabditis elegans. J. Mol. Biol. 333, 237-247. https://doi.org/10.1016/j.jmb.2003.08.055
  15. Im, S. H. and Lee, J. (2003) Identification of HMG-5 as a doublestranded telomeric DNA-binding protein in the nematode Caenorhabditis elegans. FEBS Lett. 554, 455-461. https://doi.org/10.1016/S0014-5793(03)01191-8
  16. Kamath, R. S. and Ahringer, J. (2003) Genome-wide RNAi screening in Caenorhabditis elegans. Methods 30, 313-321. https://doi.org/10.1016/S1046-2023(03)00050-1
  17. Kamath, R. S., Fraser, A. G., Dong, Y., Poulin, G., Durbin, R., Gotta, M., Kanapin, A., Le Bot, N., Moreno, S., Sohrmann, M. et al. (2003) Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 421, 231-237. https://doi.org/10.1038/nature01278
  18. Kim, S. K., Lund, J., Kiraly, M., Duke, K., Jiang, M., Stuart, J. M., Eizinger, A., Wylie, B. N. and Davidson, G. S. (2001) A gene expression map for Caenorhabditis elegans. Science 293, 2087-2092. https://doi.org/10.1126/science.1061603
  19. Kirouac, M. and Sternberg, P. W. (2003) cis-Regulatory control of three cell fate-specific genes in vulval organogenesis of Caenorhabditis elegans and C. briggsae. Dev. Biol. 257, 85-103. https://doi.org/10.1016/S0012-1606(03)00032-0
  20. Kuwabara, P. E. and Shah, S. (1994) Cloning by synteny: identifying C. briggsae homologues of C. elegans genes. Nucleic Acids Res. 22, 4414-4418. https://doi.org/10.1093/nar/22.21.4414
  21. Kwon, J., Hong, M., Choi, M., Kang, S., Duke, K., Kim, S., Lee, S. and Lee, J. (2004) Ethanol response genes and their regulation analyzed by microarray and comparative genomic approach in the nematode Caenorhabditis elegans. Genomics in press.
  22. Lee, S. S., Lee, R. Y., Fraser, A. G., Kamath, R. S., Ahringer, J. and Ruvkun, G. (2003) A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity. Nat. Genet. 33, 40-48. https://doi.org/10.1038/ng1056
  23. Link, C. D., Taft, A., Kapulkin, V., Duke, K., Kim, S., Fei, Q., Wood, D. E. and Sahagan, B. G. (2003) Gene expression analysis in a transgenic Caenorhabditis elegans Alzheimer's disease model. Neurobiol. Aging 24, 397-413. https://doi.org/10.1016/S0197-4580(02)00224-5
  24. Madi, A., Mikkat, S., Ringel, B., Ulbrich, M., Thiesen, H. J. and Glocker, M. O. (2003) Mass spectrometric proteome analysis for profiling temperature-dependent changes of protein expression in wild-type Caenorhabditis elegans. Proteomics 3, 1526-1534. https://doi.org/10.1002/pmic.200300490
  25. Maeda, I., Kohara, Y., Yamamoto, M. and Sugimoto, A. (2001) Large-scale analysis of gene function in Caenorhabditis elegans by high- throughput RNAi. Curr. Biol. 11, 171-176. https://doi.org/10.1016/S0960-9822(01)00052-5
  26. Murphy, C. T., McCarroll, S. A., Bargmann, C. I., Fraser, A., Kamath, R. S., Ahringer, J., Li, H. and Kenyon, C. (2003) Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424, 277-283. https://doi.org/10.1038/nature01789
  27. Piano, F., Schetter, A. J., Mangone, M., Stein, L. and Kemphues, K. J. (2000) RNAi analysis of genes expressed in the ovary of Caenorhabditis elegans. Curr. Biol. 10, 1619-1622. https://doi.org/10.1016/S0960-9822(00)00869-1
  28. Reinke, V. (2002) Functional exploration of the C. elegans genome using DNA microarrays. Nat. Genet. 32 Suppl, 541-546. https://doi.org/10.1038/ng1039
  29. Reinke, V., Smith, H. E., Nance, J., Wang, J., Van Doren, C., Begley, R., Jones, S. J., Davis, E. B., Scherer, S., Ward, S. and Kim, S. K. (2000) A global profile of germline gene expression in C. elegans. Mol. Cell 6, 605-616. https://doi.org/10.1016/S1097-2765(00)00059-9
  30. Romagnolo, B., Jiang, M., Kiraly, M., Breton, C., Begley, R., Wang, J., Lund, J. and Kim, S. K. (2002) Downstream targets of let-60 Ras in Caenorhabditis elegans. Dev. Biol. 247, 127-136. https://doi.org/10.1006/dbio.2002.0692
  31. Simmer, F., Moorman, C., Van Der Linden, A. M., Kuijk, E., Van Den Berghe, P. V., Kamath, R., Fraser, A. G., Ahringer, J. and Plasterk, R. H. (2003) Genome-wide RNAi of C. elegans using the hypersensitive rrf-3 strain reveals novel gene functions. PLoS Biol. 1, E12.
  32. Stein, L. D., Bao, Z., Blasiar, D., Blumenthal, T., Brent, M. R., Chen, N., Chinwalla, A., Clarke, L., Clee, C., Coghlan, A. et al. (2003) The genome sequence of Caenorhabditis briggsae: A platform for comparative genomics. PLoS Biol. 1, E45.
  33. Stuart, J. M., Segal, E., Koller, D. and Kim, S. K. (2003) A genecoexpression network for global discovery of conserved genetic modules. Science 302, 249-255. https://doi.org/10.1126/science.1087447
  34. Tabara, H., Grishok, A. and Mello, C. C. (1998) RNAi in C. elegans: soaking in the genome sequence. Science 282, 430-431. https://doi.org/10.1126/science.282.5388.430
  35. Tavernarakis, N., Wang, S. L., Dorovkov, M., Ryazanov, A. and Driscoll, M. (2000) Heritable and inducible genetic interference by double-stranded RNA encoded by transgenes. Nat. Genet. 24, 180-183. https://doi.org/10.1038/72850
  36. Timmons, L. and Fire, A. (1998) Specific interference by ingested dsRNA. Nature 395, 854. https://doi.org/10.1038/27579
  37. Wang, J. and Kim, S. K. (2003) Global analysis of dauer gene expression in Caenorhabditis elegans. Development 130, 1621-1634. https://doi.org/10.1242/dev.00363
  38. Zhang, Y., Ma, C., Delohery, T., Nasipak, B., Foat, B. C., Bounoutas, A., Bussemaker, H. J., Kim, S. K. and Chalfie, M. (2002) Identification of genes expressed in C. elegans touch receptor neurons. Nature 418, 331-335. https://doi.org/10.1038/nature00891

Cited by

  1. A biochemist’s guide to Caenorhabditis elegans vol.359, pp.1, 2006, https://doi.org/10.1016/j.ab.2006.07.033
  2. Gene silencing in human embryonic stem cells by RNA interference vol.390, pp.4, 2009, https://doi.org/10.1016/j.bbrc.2009.10.038
  3. A genome–wide screen to identify genes controlling the rate of entry into mitosis in fission yeast vol.15, pp.22, 2016, https://doi.org/10.1080/15384101.2016.1242535
  4. Emerging Technologies: Trendy RNA Tools for Aging Research vol.59, pp.8, 2004, https://doi.org/10.1093/gerona/59.8.B771
  5. Core RNAi machinery and gene knockdown in the emerald ash borer (Agrilus planipennis) vol.72, 2015, https://doi.org/10.1016/j.jinsphys.2014.12.002
  6. Insights to transcriptional networks by using high throughput RNAi strategies vol.9, pp.1, 2010, https://doi.org/10.1093/bfgp/elp046
  7. Identification and functional validation of therapeutic targets for malignant melanoma vol.72, pp.3, 2009, https://doi.org/10.1016/j.critrevonc.2009.02.004
  8. Genomic Regulatory Networks and Animal Development vol.9, pp.4, 2005, https://doi.org/10.1016/j.devcel.2005.09.005