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Proceedings of the Royal Society B: Biological Sciences logoLink to Proceedings of the Royal Society B: Biological Sciences
. 2004 Jan 7;271(1534):89–96. doi: 10.1098/rspb.2003.2560

Duplicate genes and robustness to transient gene knock-downs in Caenorhabditis elegans.

Gavin C Conant 1, Andreas Wagner 1
PMCID: PMC1691561  PMID: 15002776

Abstract

We examine robustness to mutations in the nematode worm Caenorhabditis elegans and the role of single-copy and duplicate genes in it. We do so by integrating complete genome sequence and microarray gene expression data with results from a genome-scale study using RNA interference (RNAi) to temporarily eliminate the functions of more than 16000 worm genes. We found that 89% of single-copy and 96% of duplicate genes show no detectable phenotypic effect in an RNAi knock-down experiment. We find that mutational robustness is greatest for closely related gene duplicates, large gene families and similarly expressed genes. We discuss the different causes of mutational robustness in single-copy and duplicate genes, as well as its evolutionary origin.

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Selected References

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  1. Benton B. K., Tinkelenberg A. H., Jean D., Plump S. D., Cross F. R. Genetic analysis of Cln/Cdc28 regulation of cell morphogenesis in budding yeast. EMBO J. 1993 Dec 15;12(13):5267–5275. doi: 10.1002/j.1460-2075.1993.tb06222.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bernardi G., Bernardi G. Compositional constraints and genome evolution. J Mol Evol. 1986;24(1-2):1–11. doi: 10.1007/BF02099946. [DOI] [PubMed] [Google Scholar]
  3. Comeron J. M., Aguadé M. An evaluation of measures of synonymous codon usage bias. J Mol Evol. 1998 Sep;47(3):268–274. doi: 10.1007/pl00006384. [DOI] [PubMed] [Google Scholar]
  4. Conant Gavin C., Wagner Andreas. Asymmetric sequence divergence of duplicate genes. Genome Res. 2003 Sep;13(9):2052–2058. doi: 10.1101/gr.1252603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Conant Gavin C., Wagner Andreas. GenomeHistory: a software tool and its application to fully sequenced genomes. Nucleic Acids Res. 2002 Aug 1;30(15):3378–3386. doi: 10.1093/nar/gkf449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cooke J., Nowak M. A., Boerlijst M., Maynard-Smith J. Evolutionary origins and maintenance of redundant gene expression during metazoan development. Trends Genet. 1997 Sep;13(9):360–364. doi: 10.1016/s0168-9525(97)01233-x. [DOI] [PubMed] [Google Scholar]
  7. Edwards J. S., Palsson B. O. The Escherichia coli MG1655 in silico metabolic genotype: its definition, characteristics, and capabilities. Proc Natl Acad Sci U S A. 2000 May 9;97(10):5528–5533. doi: 10.1073/pnas.97.10.5528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fire A., Xu S., Montgomery M. K., Kostas S. A., Driver S. E., Mello C. C. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature. 1998 Feb 19;391(6669):806–811. doi: 10.1038/35888. [DOI] [PubMed] [Google Scholar]
  9. Goldman N., Yang Z. A codon-based model of nucleotide substitution for protein-coding DNA sequences. Mol Biol Evol. 1994 Sep;11(5):725–736. doi: 10.1093/oxfordjournals.molbev.a040153. [DOI] [PubMed] [Google Scholar]
  10. Gu Zhenglong, Nicolae Dan, Lu Henry H-S, Li Wen Hsiung. Rapid divergence in expression between duplicate genes inferred from microarray data. Trends Genet. 2002 Dec;18(12):609–613. doi: 10.1016/s0168-9525(02)02837-8. [DOI] [PubMed] [Google Scholar]
  11. Gu Zhenglong, Steinmetz Lars M., Gu Xun, Scharfe Curt, Davis Ronald W., Li Wen-Hsiung. Role of duplicate genes in genetic robustness against null mutations. Nature. 2003 Jan 2;421(6918):63–66. doi: 10.1038/nature01198. [DOI] [PubMed] [Google Scholar]
  12. Hanks M., Wurst W., Anson-Cartwright L., Auerbach A. B., Joyner A. L. Rescue of the En-1 mutant phenotype by replacement of En-1 with En-2. Science. 1995 Aug 4;269(5224):679–682. doi: 10.1126/science.7624797. [DOI] [PubMed] [Google Scholar]
  13. Hill A. A., Hunter C. P., Tsung B. T., Tucker-Kellogg G., Brown E. L. Genomic analysis of gene expression in C. elegans. Science. 2000 Oct 27;290(5492):809–812. doi: 10.1126/science.290.5492.809. [DOI] [PubMed] [Google Scholar]
  14. Hubbard T. J., Ailey B., Brenner S. E., Murzin A. G., Chothia C. SCOP, Structural Classification of Proteins database: applications to evaluation of the effectiveness of sequence alignment methods and statistics of protein structural data. Acta Crystallogr D Biol Crystallogr. 1998 Nov 1;54(Pt 6 1):1147–1154. doi: 10.1107/s0907444998009172. [DOI] [PubMed] [Google Scholar]
  15. Kamath Ravi S., Fraser Andrew G., Dong Yan, Poulin Gino, Durbin Richard, Gotta Monica, Kanapin Alexander, Le Bot Nathalie, Moreno Sergio, Sohrmann Marc. Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature. 2003 Jan 16;421(6920):231–237. doi: 10.1038/nature01278. [DOI] [PubMed] [Google Scholar]
  16. Kim S. K., Lund J., Kiraly M., Duke K., Jiang M., Stuart J. M., Eizinger A., Wylie B. N., Davidson G. S. A gene expression map for Caenorhabditis elegans. Science. 2001 Sep 14;293(5537):2087–2092. doi: 10.1126/science.1061603. [DOI] [PubMed] [Google Scholar]
  17. Li W. H., Gu Z., Wang H., Nekrutenko A. Evolutionary analyses of the human genome. Nature. 2001 Feb 15;409(6822):847–849. doi: 10.1038/35057039. [DOI] [PubMed] [Google Scholar]
  18. Li X., Noll M. Evolution of distinct developmental functions of three Drosophila genes by acquisition of different cis-regulatory regions. Nature. 1994 Jan 6;367(6458):83–87. doi: 10.1038/367083a0. [DOI] [PubMed] [Google Scholar]
  19. Lynch M., Conery J. S. The evolutionary fate and consequences of duplicate genes. Science. 2000 Nov 10;290(5494):1151–1155. doi: 10.1126/science.290.5494.1151. [DOI] [PubMed] [Google Scholar]
  20. Muse S. V., Gaut B. S. A likelihood approach for comparing synonymous and nonsynonymous nucleotide substitution rates, with application to the chloroplast genome. Mol Biol Evol. 1994 Sep;11(5):715–724. doi: 10.1093/oxfordjournals.molbev.a040152. [DOI] [PubMed] [Google Scholar]
  21. Nasmyth K. Control of the yeast cell cycle by the Cdc28 protein kinase. Curr Opin Cell Biol. 1993 Apr;5(2):166–179. doi: 10.1016/0955-0674(93)90099-c. [DOI] [PubMed] [Google Scholar]
  22. Nowak M. A., Boerlijst M. C., Cooke J., Smith J. M. Evolution of genetic redundancy. Nature. 1997 Jul 10;388(6638):167–171. doi: 10.1038/40618. [DOI] [PubMed] [Google Scholar]
  23. Pál C., Papp B., Hurst L. D. Highly expressed genes in yeast evolve slowly. Genetics. 2001 Jun;158(2):927–931. doi: 10.1093/genetics/158.2.927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Pál Csaba, Papp Balázs, Hurst Laurence D. Genomic function: Rate of evolution and gene dispensability. Nature. 2003 Jan 30;421(6922):496–498. doi: 10.1038/421496b. [DOI] [PubMed] [Google Scholar]
  25. Qian J., Luscombe N. M., Gerstein M. Protein family and fold occurrence in genomes: power-law behaviour and evolutionary model. J Mol Biol. 2001 Nov 2;313(4):673–681. doi: 10.1006/jmbi.2001.5079. [DOI] [PubMed] [Google Scholar]
  26. Rubin G. M., Yandell M. D., Wortman J. R., Gabor Miklos G. L., Nelson C. R., Hariharan I. K., Fortini M. E., Li P. W., Apweiler R., Fleischmann W. Comparative genomics of the eukaryotes. Science. 2000 Mar 24;287(5461):2204–2215. doi: 10.1126/science.287.5461.2204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Seoighe C., Wolfe K. H. Yeast genome evolution in the post-genome era. Curr Opin Microbiol. 1999 Oct;2(5):548–554. doi: 10.1016/s1369-5274(99)00015-6. [DOI] [PubMed] [Google Scholar]
  28. Smith V., Chou K. N., Lashkari D., Botstein D., Brown P. O. Functional analysis of the genes of yeast chromosome V by genetic footprinting. Science. 1996 Dec 20;274(5295):2069–2074. doi: 10.1126/science.274.5295.2069. [DOI] [PubMed] [Google Scholar]
  29. Stein L., Sternberg P., Durbin R., Thierry-Mieg J., Spieth J. WormBase: network access to the genome and biology of Caenorhabditis elegans. Nucleic Acids Res. 2001 Jan 1;29(1):82–86. doi: 10.1093/nar/29.1.82. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Steinmetz Lars M., Scharfe Curt, Deutschbauer Adam M., Mokranjac Dejana, Herman Zelek S., Jones Ted, Chu Angela M., Giaever Guri, Prokisch Holger, Oefner Peter J. Systematic screen for human disease genes in yeast. Nat Genet. 2002 Jul 22;31(4):400–404. doi: 10.1038/ng929. [DOI] [PubMed] [Google Scholar]
  31. Toda T., Cameron S., Sass P., Zoller M., Wigler M. Three different genes in S. cerevisiae encode the catalytic subunits of the cAMP-dependent protein kinase. Cell. 1987 Jul 17;50(2):277–287. doi: 10.1016/0092-8674(87)90223-6. [DOI] [PubMed] [Google Scholar]
  32. Wagner A. Decoupled evolution of coding region and mRNA expression patterns after gene duplication: implications for the neutralist-selectionist debate. Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6579–6584. doi: 10.1073/pnas.110147097. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wagner A. Robustness against mutations in genetic networks of yeast. Nat Genet. 2000 Apr;24(4):355–361. doi: 10.1038/74174. [DOI] [PubMed] [Google Scholar]
  34. Wagner A. The role of population size, pleiotropy and fitness effects of mutations in the evolution of overlapping gene functions. Genetics. 2000 Mar;154(3):1389–1401. doi: 10.1093/genetics/154.3.1389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wagner A. The yeast protein interaction network evolves rapidly and contains few redundant duplicate genes. Mol Biol Evol. 2001 Jul;18(7):1283–1292. doi: 10.1093/oxfordjournals.molbev.a003913. [DOI] [PubMed] [Google Scholar]
  36. Wagner Andreas. Asymmetric functional divergence of duplicate genes in yeast. Mol Biol Evol. 2002 Oct;19(10):1760–1768. doi: 10.1093/oxfordjournals.molbev.a003998. [DOI] [PubMed] [Google Scholar]
  37. Wang Y., Schnegelsberg P. N., Dausman J., Jaenisch R. Functional redundancy of the muscle-specific transcription factors Myf5 and myogenin. Nature. 1996 Feb 29;379(6568):823–825. doi: 10.1038/379823a0. [DOI] [PubMed] [Google Scholar]
  38. Winzeler E. A., Shoemaker D. D., Astromoff A., Liang H., Anderson K., Andre B., Bangham R., Benito R., Boeke J. D., Bussey H. Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science. 1999 Aug 6;285(5429):901–906. doi: 10.1126/science.285.5429.901. [DOI] [PubMed] [Google Scholar]
  39. Wright F. The 'effective number of codons' used in a gene. Gene. 1990 Mar 1;87(1):23–29. doi: 10.1016/0378-1119(90)90491-9. [DOI] [PubMed] [Google Scholar]

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