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The 2R hypothesis and the human genome sequence

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Journal of Structural and Functional Genomics

Abstract

One theory formalised in 1970 proposes that the complexity of vertebrate genomes originated by means of genome duplication at the base of the vertebrate lineage. Since then, the theory has remained both popular and controversial. Here we review the theory, and present preliminary results from our analysis of duplications in the draft human genome sequence. We find evidence for extensive duplication of parts of the genome. We also question the validity of the 'parsimony test' that has been used in other analyses.

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References

  • Allendorf, F.W. and Thorgaard, G.H. (1984) Tetraploidy and the evolution of salmonid fishes. In Evolutionary Genetics of Fishes (Ed. Turner, B.), Plenum Press, New York, NY, pp. 1-46.

    Google Scholar 

  • Bailey, W.J., Kim, J., Wagner, G.P. and Ruddle, F.H. (1997) Phylogenetic reconstruction of vertebrate Hox cluster duplications. Mol. Biol. Evol., 14, 843-853.

    Google Scholar 

  • Bairoch, A. and Apweiler, R. (2000) The SWISS-PROT protein sequence database and its supplement TrEMBL in 2000. Nucleic Acids Res., 28, 45-48.

    Google Scholar 

  • Birney, E. and Durbin, R. (2000) Using GeneWise in the Drosophila annotation experiment. Genome Res., 10, 547-548.

    Google Scholar 

  • Burge, C. and Karlin, S. (1997) Prediction of complete gene structures in human genomic DNA. J. Mol. Biol., 268, 78-94.

    Google Scholar 

  • Comings, D.E. (1972) Evidence for ancient tetraploidy and conservation of linkage groups in mammalian chromosomes. Nature, 238, 455-457.

    Google Scholar 

  • Delcher, A.L., Kasif, S., Fleischmann, R.D., Peterson, J., White, O. and Salzberg, S.L. (1999) Alignment of whole genomes. Nucleic Acids Res., 27, 2369-2376.

    Google Scholar 

  • Deloukas, P., et al. (2001) The DNA sequence and comparative analysis of human chromosome 20. Nature, 414, 865-871.

    Google Scholar 

  • .Endo, T., Imanishi, T., Gojobori, T. and Inoko, H. (1997) Evolutionary significance of intra-genome duplications on human chromosomes. Gene, 205, 19-27.

    Google Scholar 

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

    Google Scholar 

  • Friedman, R. and Hughes, A.L. (2001) Gene duplication and the structure of eukaryotic genomes. Genome Res., 11, 373-381.

    Google Scholar 

  • Gallardo, M.H., Bickham, J.W., Honeycutt, R.L., Ojeda, R.A. and Kohler, N. (1999) Discovery of tetraploidy in a mammal. Nature, 401, 341.

    Google Scholar 

  • Garcia-Fernandez, J. and Holland, P.W. (1994) Archetypal organization of the amphioxus Hox gene cluster. Nature, 370, 563-566.

    Google Scholar 

  • Gaut, B.S. and Doebley, J.F. (1997) DNA sequence evidence for the segmental allotetraploid origin of maize. Proc. Natl. Acad. Sci. USA, 94, 6809-6814.

    Google Scholar 

  • Gibson, T.J. and Spring, J. (2000) Evidence in favour of ancient octaploidy in the vertebrate genome. Biochem. Soc. Trans., 28, 259-264.

    Google Scholar 

  • Graves, J.A. (1996) Mammals that break the rules: genetics of marsupials and monotremes. Annu. Rev. Genet., 30, 233-260.

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  • Hubbard, T., et al. (2002) The Ensembl genome database project. Nucleic Acids Res., 30, 38-41.

    Google Scholar 

  • 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 

  • Hughes, A.L. (1999) 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 

  • 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 

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

    Google Scholar 

  • Kappen, C., Schughart, K. and Ruddle, F.H. (1989) Two steps in the evolution of Antennapedia-class vertebrate homeobox genes. Proc. Natl. Acad. Sci. USA, 86, 5459-5463.

    Google Scholar 

  • Kasahara, M. (1997) New insights into the genomic organization and origin of the major histocompatibility complex: role of chromosomal (genome) duplication in the emergence of the adaptive immune system. Hereditas, 127, 59-65.

    Google Scholar 

  • Kasahara, M., Hayashi, M., Tanaka, K., Inoko, H., Sugaya, K., Ikemura, T. and Ishibashi, T. (1996) Chromosomal localization of the proteasome Z subunit gene reveals an ancient chromosomal duplication involving the major histocompatibility complex. Proc. Natl. Acad. Sci. USA, 93, 9096-9101.

    Google Scholar 

  • Katsanis, N., Fitzgibbon, J. and Fisher, E.M.C. (1996) Paralogy mapping: identification of a region in the human MHC triplicated onto human chromosomes 1 and 9 allows the prediction and isolation of novel PBX and NOTCH loci. Genomics, 35, 101-108.

    Google Scholar 

  • Kent, W.J. and Haussler, D. (2001) Assembly of the working draft of the human genome with GigAssembler. Genome Res., 11, 1541-1548.

    Google Scholar 

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

    Google Scholar 

  • Lahn, B.T. and Page, D.C. (1999) Four evolutionary strata on the human X chromosome. Science, 286, 964-967.

    Google Scholar 

  • Lundin, L.G. (1993) Evolution of the vertebrate genome as re-flected in paralogous chromosomal regions in man and the house mouse. Genomics, 16, 1-19.

    Google Scholar 

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

    Google Scholar 

  • Martin, A.P. (1999) Increasing genomic complexity by gene duplication and the origin of vertebrates. Amer. Nat., 154, 111-128.

    Google Scholar 

  • Martin, G.R., Richman, M., Reinsch, S., Nadeau, J.H. and Joyner, A. (1990) Mapping of the two mouse engrailed-like genes: close linkage of En-1 to dominant hemimelia (Dh) on chromosome 1 and of En-2 to hemimelic extratoes (Hx) on chromosome 5. Genomics, 6, 302-308.

    Google Scholar 

  • Martinez-Perez, E., Shaw, P. and Moore, G. (2001) The Ph1 locus is needed to ensure specific somatic and meiotic centromere association. Nature, 411, 204-207.

    Google Scholar 

  • McLysaght, A., Hokamp, K. and Wolfe, K.H. (2002) Extensive genomic duplication during early chordate evolution. Nature Genet., 31, 200-204.

    Google Scholar 

  • Meyer, A. and Schartl, M. (1999) Gene and genome duplications 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 

  • Muller, H.J. (1925) Why polyploidy is rarer in animals than in plants. Amer. Nat., 9, 346-353.

    Google Scholar 

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

    Google Scholar 

  • Ohno, S. (1999) Gene duplication and the uniqueness of vertebrate genomes circa 1970-1999. Semin. Cell Devel. Biol., 10, 517-522.

    Google Scholar 

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

    Google Scholar 

  • Pohlmann, R. and Philippsen, P. (1996) Sequencing a cosmid clone of Saccharomyces cerevisiae chromosome XIV reveals 12 new open reading frames (ORFs) and an ancient duplication of six ORFs. Yeast, 12, 391-402.

    Google Scholar 

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

    Google Scholar 

  • Riley, R. and Kempanna, C. (1963) The homeologous nature of the non-homologous meiotic pairing in Triticum aestivum deficient for chromosome V (5B) Heredity, 18, 287-306.

    Google Scholar 

  • Sato, H., Tanaka, M., Takino, T., Inoue, M. and Seiki, M. (1997) Assignment of the human genes for membrane-type-1,-2, and-3 matrix metalloproteinases (MMP14, MMP15, and MMP16) to 14q12.2, 16q12.2-q21, and 8q21, respectively, by in situ hybridization. Genomics, 39, 412-413.

    Google Scholar 

  • Seoighe, C. and Wolfe, K.H. (1998) Extent of genomic rearrangement after genome duplication in yeast. Proc. Natl. Acad. Sci. USA, 95, 4447-4452.

    Google Scholar 

  • Sidow, A. (1996) Gen(om)e duplications in the evolution of early vertebrates. Curr. Opin. Genet. Devel., 6, 715-722.

    Google Scholar 

  • Skrabanek, L. and Wolfe, K.H. (1998) Eukaryote genome duplication-where's the evidence? Curr. Opin. Genet. Devel., 8, 694-700.

    Google Scholar 

  • Smith, N.G.C., Knight, R. and Hurst, L.D. (1999) Vertebrate genome evolution: a slow shuffle or a big bang? BioEssays, 21, 697-703.

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  • Vision, T.J., Brown, D.G. and Tanksley, S.D. (2000) The origins of genomic duplications in Arabidopsis. Science, 290, 2114-2117.

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  • Zhang, J. and Nei, M. (1996) Evolution of Antennapedia-class homeobox genes. Genetics, 142, 295-303.

    Google Scholar 

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Correspondence to Kenneth H. Wolfe.

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Hokamp, K., McLysaght, A. & Wolfe, K.H. The 2R hypothesis and the human genome sequence. J Struct Func Genom 3, 95–110 (2003). https://doi.org/10.1023/A:1022661917301

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