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Extensive genomic duplication during early chordate evolution

Nature Genetics volume 31, pages 200–204 (2002)Cite this article

Abstract

Opinions on the hypothesis1 that ancient genome duplications contributed to the vertebrate genome range from strong skepticism2,3,4 to strong credence5,6,7. Previous studies concentrated on small numbers of gene families or chromosomal regions that might not have been representative of the whole genome4,5, or used subjective methods to identify paralogous genes and regions5,8. Here we report a systematic and objective analysis of the draft human genome sequence to identify paralogous chromosomal regions (paralogons) formed during chordate evolution and to estimate the ages of duplicate genes. We found that the human genome contains many more paralogons than would be expected by chance. Molecular clock analysis of all protein families in humans that have orthologs in the fly and nematode indicated that a burst of gene duplication activity took place in the period 350–650 Myr ago and that many of the duplicate genes formed at this time are located within paralogons. Our results support the contention that many of the gene families in vertebrates were formed or expanded by large-scale DNA duplications in an early chordate. Considering the incompleteness of the sequence data and the antiquity of the event, the results are compatible with at least one round of polyploidy.

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Figure 1: Paralogons on human chromosome 17.
Figure 2: Estimation of gene duplication dates using linearized trees18 with fly and nematode outgroups.
Figure 3: Comparison of topology-based and molecular clock–based estimation of the dates of gene duplication for 36 human gene pairs.

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References

  1. Ohno, S. Evolution by Gene Duplication (George Allen and Unwin, London, 1970).

    Book  Google Scholar 

  2. Martin, A. Is tetralogy true? Lack of support for the 'one-to-four' rule. Mol. Biol. Evol. 18, 89–93 (2001).

    Article  CAS  Google Scholar 

  3. Friedman, R. & Hughes, A.L. Pattern and timing of gene duplication in animal genomes. Genome Res. 11, 1842–1847 (2001).

    Article  CAS  Google Scholar 

  4. Hughes, A.L., da Silva, J. & Friedman, R. Ancient genome duplications did not structure the human Hox-bearing chromosomes. Genome Res. 11, 771–780 (2001).

    Article  CAS  Google Scholar 

  5. Thornton, J.W. Evolution of vertebrate steroid receptors from an ancestral estrogen receptor by ligand exploitation and serial genome expansions. Proc. Natl Acad. Sci. USA 98, 5671–5676 (2001).

    Article  CAS  Google Scholar 

  6. Spring, J. Vertebrate evolution by interspecific hybridisation-are we polyploid? FEBS Lett. 400, 2–8 (1997).

    Article  CAS  Google Scholar 

  7. Holland, P.W.H., Garcia-Fernandez, J., Williams, N.A. & Sidow, A. Gene duplications and the origins of vertebrate development. Development Suppl., 125–133 (1994).

  8. Popovici, C., Leveugle, M., Birnbaum, D. & Coulier, F. Coparalogy: physical and functional clusterings in the human genome. Biochem. Biophys. Res. Commun. 288, 362–370 (2001).

    Article  CAS  Google Scholar 

  9. International Human Genome Sequencing Consortium. Initial sequencing and analysis of the human genome. Nature 409, 860–921 (2001).

  10. Koh, Y.S. & Moore, D.D. Linkage of the nuclear hormone receptor genes NR1D2, THRB, and RARB: evidence for an ancient, large-scale duplication. Genomics 57, 289–292 (1999).

    Article  CAS  Google Scholar 

  11. Smith, N.G.C., Knight, R. & Hurst, L.D. Vertebrate genome evolution: a slow shuffle or a big bang? Bioessays 21, 697–703 (1999).

    Article  CAS  Google Scholar 

  12. Venter, J.C. et al. The sequence of the human genome. Science 291, 1304–1351 (2001).

    Article  CAS  Google Scholar 

  13. Ruddle, F.H., Bentley, K.L., Murtha, M.T. & Risch, N. Gene loss and gain in the evolution of the vertebrates. Development Suppl., 155–161 (1994).

  14. Flajnik, M.F. & Kasahara, M. Comparative genomics of the MHC: glimpses into the evolution of the adaptive immune system. Immunity 15, 351–362 (2001).

    Article  CAS  Google Scholar 

  15. Pébusque, M.-J., Coulier, F., Birnbaum, D. & Pontarotti, P. Ancient large scale genome duplications: phylogenetic and linkage analyses shed light on chordate genome evolution. Mol. Biol. Evol. 15, 1145–1159 (1998).

    Article  Google Scholar 

  16. Kojima, S., Itoh, Y., Matsumoto, S., Masuho, Y. & Seiki, M. Membrane-type 6 matrix metalloproteinase (MT6-MMP, MMP-25) is the second glycosyl-phosphatidyl inositol (GPI)-anchored MMP. FEBS Lett. 480, 142–146 (2000).

    Article  CAS  Google Scholar 

  17. Tomsig, J.L. & Creutz, C.E. Biochemical characterization of copine: a ubiquitous Ca2+-dependent, phospholipid-binding protein. Biochemistry 39, 16163–16175 (2000).

    Article  CAS  Google Scholar 

  18. Takezaki, N., Rzhetsky, A. & Nei, M. Phylogenetic test of the molecular clock and linearized trees. Mol. Biol. Evol. 12, 823–833 (1995).

    CAS  PubMed  Google Scholar 

  19. Nei, M., Xu, P. & Glazko, G. Estimation of divergence times from multiprotein sequences for a few mammalian species and several distantly related organisms. Proc. Natl Acad. Sci. USA 98, 2497–2502 (2001).

    Article  CAS  Google Scholar 

  20. Wang, D.Y., Kumar, S. & Hedges, S.B. Divergence time estimates for the early history of animal phyla and the origin of plants, animals and fungi. Proc. R. Soc. Lond. B 266, 163–171 (1999).

    Article  CAS  Google Scholar 

  21. Miyata, T. & Suga, H. Divergence pattern of animal gene families and relationship with the Cambrian explosion. Bioessays 23, 1018–1027 (2001).

    Article  CAS  Google Scholar 

  22. Gu, X., Wang, Y. & Gu, J. Age distribution of human gene families showing significant roles of both large- and small-scale duplications in vertebrate evolution. Nature Genet. 31, 205–209 (2002); advance online publication 28 May 2002 (DOI: 10.1038/ng902).

    Article  CAS  Google Scholar 

  23. Wolfe, K.H. Yesterday's polyploids and the mystery of diploidization. Nature Reviews Genet. 2, 333–341 (2001).

    Article  CAS  Google Scholar 

  24. Makalowski, W. Are we polyploids? A brief history of one hypothesis. Genome Res. 11, 667–670 (2001).

    Article  CAS  Google Scholar 

  25. Hughes, A.L. Phylogenetic tests of the hypothesis of block duplication of homologous genes on human chromosomes 6, 9, and 1. Mol. Biol. Evol. 15, 854–870 (1998).

    Article  CAS  Google Scholar 

  26. Gu, X. & Huang, W. Testing the parsimony test of genome duplications: a counterexample. Genome Res. 12, 1–2 (2002).

    Article  CAS  Google Scholar 

  27. Wolfe, K.H. & Shields, D.C. Molecular evidence for an ancient duplication of the entire yeast genome. Nature 387, 708–713 (1997).

    Article  CAS  Google Scholar 

  28. Arabidopsis Genome Initiative. Analysis of the genome sequence of the flowering plant Arabidopsis thaliana. Nature 408, 796–815 (2000).

  29. Notredame, C., Higgins, D.G. & Heringa, J. T-Coffee: a novel method for fast and accurate multiple sequence alignment. J. Mol. Biol. 302, 205–217 (2000).

    Article  CAS  Google Scholar 

  30. Gu, X. & Zhang, J. A simple method for estimating the parameter of substitution rate variation among sites. Mol. Biol. Evol. 14, 1106–1113 (1997).

    Article  CAS  Google Scholar 

  31. Kumar, S. & Hedges, S.B. A molecular timescale for vertebrate evolution. Nature 392, 917–920 (1998).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank D.C. Shields, A. Coghlan, A.T. Lloyd and other members of the Wednesday lunch group for discussion. This work was supported by the Health Research Board (Ireland), a Trinity College Dublin High Performance Computing studentship award and Science Foundation Ireland.

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Author notes

  1. Aoife McLysaght, Karsten Hokamp and Kenneth H. Wolfe: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Genetics, Smurfit Institute, University of Dublin, Trinity College, Dublin, 2, Ireland

    Aoife McLysaght, Karsten Hokamp & Kenneth H. Wolfe

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  1. Aoife McLysaght
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  2. Karsten Hokamp
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  3. Kenneth H. Wolfe
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Correspondence to Kenneth H. Wolfe.

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McLysaght, A., Hokamp, K. & Wolfe, K. Extensive genomic duplication during early chordate evolution. Nat Genet 31, 200–204 (2002). https://doi.org/10.1038/ng884

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