2R or not 2R: Testing hypotheses of genome duplication in early vertebrates



The widely popular hypothesis that there were two rounds of genome duplication by polyploidization early in vertebrate history (the 2R hypothesis) has been difficult to test until recently. Among the lines of evidence adduced in support of this hypothesis are relative genome size, relative gene number, and the existence of genomic regions putatively duplicated during polyploidization. The availability of sequence for a substantial portion of the human genome makes possible the first rigorous tests of this hypothesis. Comparison of gene family size in the human genome and in invertebrate genomes shows no evidence of a 4:1 ratio between vertebrates and invertebrates. Furthermore, explicit phylogenetic tests for the topology expected from two rounds of polyploidization have revealed alternative topologies in a substantial majority of human gene families. Likewise, phylogenetic analyses have shown that putatively duplicated genomic regions often include genes duplicated at widely different times over the evolution of life. The 2R hypothesis thus can be decisively rejected. Rather, current evidence favors a model of genome evolution in which tandem duplication, whether of genomic segments or of individual genes, predominates.

gene duplication gene number genome size polyploidy vertebrate evolution 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bork, P. and Copley, R. (2001) Filling in the gaps. Nature, 409, 818-820.Google Scholar
  2. Diaz, M.O., Pomykala, H.M., Bohlander, S.K., Maltepe, E., Malik, K., Brownsein, B. and Olapede, O.I. (1994) Structure of the human type-I interferon gene cluster determined from a YAC clone contig. Genomics, 22, 540-552.Google Scholar
  3. Felsenstein, J. (1985) Confidence limits on phylogenies: an approach using the bootstrap. Evolution, 39, 783-791.Google Scholar
  4. Friedman, R. and Hughes, A.L. (2001) Pattern and timing of gene duplication in animal genomes. Genome Res., in press.Google Scholar
  5. Guigo, R., Muchnik, I. and Smith, T.F. (1996) Reconstruction of ancient molecular phylogeny. Mol. Phyl. Evol., 46, 189-213.Google Scholar
  6. Hughes, A.L. (1995) The evolution of the type I interferon gene family in mammals. J. Mol. Evol., 41, 539-548.Google Scholar
  7. Hughes, A.L. (1998) Phylogenetic tests of the hypothesis of block duplication of homologous genes on human chromosomes 6, 9, and 1. Mol. Biol. Evol., 15, 854-870.Google Scholar
  8. Hughes, A.L. (1999a) Adaptive Evolution of Genes and Genomes, Oxford University Press, New York, NY.Google Scholar
  9. Hughes, A.L. (1999b) Phylogenies of developmentally important proteins do not support the hypothesis of two rounds of genome duplication early in vertebrate history. J. Mol. Evol., 48, 565-576.Google Scholar
  10. Hughes, A.L. (1999c) Genomic catastrophism and the origin of vertebrate immunity. Arch. Immunol. Ther. Exper., 47, 347-353.Google Scholar
  11. Hughes, A.L. (2000) Polyploidization and vertebrate origins: a review of the evidence. In Comparative Genomics (Eds., Sankoff, S. and Nadeau, J.H.). Kluwer, Dordrecht, pp. 493-502.Google Scholar
  12. Hughes, A.L. (2001) Evolution of the integrin ? and ? protein families. J. Mol. Evol., 52, 63-72.Google Scholar
  13. Hughes, M.K. and Hughes, A.L. (1993) Evolution of duplicate genes in a tetraploid animal, Xenopus laevis. Mol. Biol. Evol., 10, 1360-1369.Google Scholar
  14. Hughes, A.L. and Roberts, R.H. (2000) Independent origin of IFN-? and IFN-? in birds and mammals. J. Interferon Cytokine Res., 20, 737-739.Google Scholar
  15. Hughes, A.L., da Silva, J. and Friedman, R. (2001) Ancient genome duplications did not structure the human Hox-bearing chromosomes. Genome Res., 11, 771-780.Google Scholar
  16. International Human Genome Sequencing Consortium. (2001) Initial sequencing and analysis of the human genome. Nature, 409, 860-891.Google Scholar
  17. Kasahara, M., Nayaka, Y., Satta, Y. and Takahata, N. (1997) Chromosomal duplication and the emergence of the adaptive immune system. Trends Genet., 13, 90-92.Google Scholar
  18. Lundin, L.G. (1993) Evolution of the vertebrate genome as re-flected in paralogous chromosome regions in man and the house mouse. Genomics, 16, 1-19.Google Scholar
  19. Maka?owski, W. (2001) Are we polyploids? A brief history of one hypothesis. Genome Res., 11, 667-670.Google Scholar
  20. Meyer, A. and Schartl, M. (1999) Gene and genome duplication in vertebrates: the one-to-four (-to-eight in fish) rule and the evolution of novel gene functions. Curr. Opin. Cell Biol., 11, 699-704.Google Scholar
  21. Ohno, S. (1970) Evolution by Gene Duplication, Springer, New York, NY.Google Scholar
  22. Saitou, N. and Nei, M. (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol. Biol. Evol., 4, 406–425.Google Scholar
  23. Sidow, A. (1996) Gen(om)e duplications in the evolution of early vertebrates. Curr. Opin. Genet. Dev., 6, 715-722.Google Scholar
  24. Simmen, M.W., Leitger, S., Clark, V.H., Jones, S.J.M. and Bird, A. (1998) Gene number in an invertebrate chordate, Ciona intestinalis. Proc. Natl. Acad. Sci. USA, 95, 4437-4440.Google Scholar
  25. Sonnenberg, A. (1993) Integrins and their ligands. Curr. Top. Microbiol. Immunol., 184, 7-35.Google Scholar
  26. Strimmer, K. and von Haeseler, A. (1996) Quartet puzzling: a quartet maximum-likelihood method for reconstructing tree topologies. Mol. Biol. Evol., 13, 964-969.Google Scholar
  27. Yeager, M. and Hughes, A.L. (1999) Evolution of the mammalian MHC: natural selkection, recombination, and convergent evolution. Immunol. Rev., 167, 45-58.Google Scholar

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  1. 1.Department of Biological SciencesUniversity of South CarolinaColumbiaUSA

Personalised recommendations