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The duplication of the Hox gene clusters in teleost fishes

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Abstract

Higher teleost fishes, including zebrafish and fugu, have duplicated their Hox genes relative to the gene inventory of other gnathostome lineages. The most widely accepted theory contends that the duplicate Hox clusters orginated synchronously during a single genome duplication event in the early history of ray-finned fishes. In this contribution we collect and re-evaluate all publicly available sequence information. In particular, we show that the short Hox gene fragments from published PCR surveys of the killifish Fundulus heteroclitus, the medaka Oryzias latipes and the goldfish Carassius auratus can be used to determine with little ambiguity not only their paralog group but also their membership in a particular cluster.

Together with a survey of the genomic sequence data from the pufferfish Tetraodon nigroviridis we show that at least percomorpha, and possibly all eutelosts, share a system of 7 or 8 orthologous Hox gene clusters. There is little doubt about the orthology of the two teleost duplicates of the HoxA and HoxB clusters. A careful analysis of both the coding sequence of Hox genes and of conserved non-coding sequences provides additional support for the “duplication early” hypothesis that the Hox clusters in teleosts are derived from eight ancestral clusters by means of subsequent gene loss; the data remain ambiguous, however, in particular for the HoxC clusters.

Assuming the “duplication early” hypothesis we use the new evidence on the Hox gene complements to determine the phylogenetic positions of gene-loss events in the wake of the cluster duplication. Surprisingly, we find that the resolution of redundancy seems to be a slow process that is still ongoing. A few suggestions on which additional sequence data would be most informative for resolving the history of the teleostean Hox genes are discussed.

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References

  • Ahn, D.-g., Gibson, G., 1999. Expression patterns of threespine stickleback Hox genes and insights into the evolution of the vertebrate body axis. Development Genes and Evolution 209, 482–494.

    Article  PubMed  CAS  Google Scholar 

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

    Google Scholar 

  • Amores, A., Force, A., Yan, Y.L., Joly, C., Amemiya, A., Fritz, R.K., Ho, J., Langeland, V., Prince, Y.L., Wang, M., Westerfield, M., Ekker, M., Postlethwait, J.H., 1988. Zebrafish Hox clusters and vertebrate genome evolution. Science 282, 1711–1714.

    Article  Google Scholar 

  • Amores, A., Suzuki, T., Yan, Y.L., Pomeroy, J., Singer, A., Amemiya, C., Postlethwait, J., 2004. Developmental roles of pufferfish Hox clusters and genome evolution in ray-fin fish. Genome Research 14, 1–10.

    Article  PubMed  CAS  Google Scholar 

  • Aparicio, S., Hawker, K., Cottage, A., Mikawa, Y., Zuo, L., Venkatesh, B., Chen, E., Krumlauf, R., Brenner, S., 1997. Organization of the Fugu rubripes Hox clusters: evidence for continuing evolution of vertebrate Hox complexes. Nature Genetics 16, 79–83.

    Article  PubMed  CAS  Google Scholar 

  • Bandelt, H.-J., Dress, A.W.M., 1993. A relational approach to split decomposition. In: Opitz, O., Lausen, B., Klar, R. (Eds.), Information and Classification. Springer, Berlin, pp. 123–131.

    Google Scholar 

  • Bryant, D., Moulton, V., 2004. Neighbor-net: an agglomerative method for the construction of phylogenetic networks. Molecular Biology and Evolution 21, 255–265.

    Article  PubMed  CAS  Google Scholar 

  • Chen, W.-J., Bonillo, C., Lecointre, G., 2003. Repeatability of clades as a criterion of reliability: a case study for molecular phylogeny of acanthomorpha (teleostei) with larger number of taxa. Molecular Phylogenetics and Evolution 26, 262–288.

    Article  PubMed  CAS  Google Scholar 

  • Chiu, C.-h., Amemiya, C., Dewar, K., Kim, C.B., Ruddle, F.H., Wagner, G.P., 2002. Molecular evolution of the HoxA cluster in the three major gnathostome lineages. Proceedings of the National Academy of Sciences of the United States of America 99, 5492–5497.

    Article  PubMed  CAS  Google Scholar 

  • Chiu, C.-H., Dewar, K., Wagner, G.P., Takahashi, K., Ruddle, F., Ledje, C., Bartsch, P., Scemama, J.-L., Stellwag, E., Fried, C., Prohaska, S.J., Stadler, P.F., Amemiya, C.T., 2004. Bichir HoxA cluster sequence reveals surprising trends in rayfinned fish genomic evolution. Genome Research 14, 11–17.

    Article  PubMed  CAS  Google Scholar 

  • Cutler, C.P., Cramb, G., 2001. Molecular physiology of osmoregulation in cels and other teleosts: the role of transporter isoforms and gene duplication. Comparative Biochemistry and Physiology 130, 551–564.

    Article  PubMed  CAS  Google Scholar 

  • Danielson, P.B., Alrubaian, J., Muller, M., Redding, J.M., Dores, R.M., 1999. Duplication of the pome gene in the paddlefish (Polyodon spathula): analysis of γ-msh, acth, and β-endorphin regions of rayfinned fish POMC. General and Comparative Endocrinology 132, 384–390.

    Google Scholar 

  • Davidson, E., 2002. Genomic Regulatory Systems. Academic Press, San Diego.

    Google Scholar 

  • Fares, M.A., Bezemer, D., Moya, A., Marín, I., 2003. Selection on coding regions determined Hox7 genes evolution. Molecular Biology and Evolution 20, 2104–2112.

    Article  PubMed  CAS  Google Scholar 

  • Felsenstein, J., 1989. Phylip—phylogeny inference package (version 3.2). Cladistics 5, 164–2166.

    Google Scholar 

  • Fjose, A., Molven, A., Eiken, H.G., 1988. Molecular cloning and characterization of homeo-box-containing genes from Atlantic salmon. Gene 62, 141–152.

    Article  PubMed  CAS  Google Scholar 

  • Force, A., Amores, A., Postlethwait, J.H., 2002. Hox cluster organization in the jawless vertebrate Petromyzon marinus. Journal of Experimental Zoology (Molecular Development and Evolution) 294, 30–46.

    Article  CAS  Google Scholar 

  • Fried, C., Prohaska, S.J., Stadler, P.F., 2003. Independent hox-cluster duplications in lampreys. Journal of Experimental Zoology (Molecular Development and Evolution) 299B, 18–25.

    Article  CAS  Google Scholar 

  • Garcia-Fernández, J., Holland, P.W., 1994. Archetypal organization of the amphioxus hox gene cluster. Nature 370, 563–566.

    Article  PubMed  Google Scholar 

  • Holland, P.W., Garcia-Fernández, J., 1996. Hox genes and chordate evolution. Developmental Biology 173, 382–395.

    Article  PubMed  CAS  Google Scholar 

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

  • Hughes, A.L., Friedman, R., 2003. 2R or not 2R: testing hypotheses of genome duplication in early vertebrates. Journal of Structural and Functional Genomics 3, 85–93.

    Article  PubMed  CAS  Google Scholar 

  • Huson, D.H., 1998. Splitstree: analyzing and visualizing evolutionary data. Bioinformatics 14, 68–73.

    Article  PubMed  CAS  Google Scholar 

  • Inoue, J.G., Miya, M., Tsukamoto, K., Nishida, M., 2003. Basal actinopterygian relationships: a mitogenomic perspective on the phylogeny of the ‘ancient fish’. Molecular Phylogenetics and Evolution 26, 110–120.

    Article  PubMed  CAS  Google Scholar 

  • Inoue, J. G., Miya, M., Tsukamoto, K., Nishida, M. 2004. Mitogenomic evidence for the monophyly of elopomorph fishes (telostei) and the evolutionary origin of the leptocephalus larva. Molecular Phylogenetics and Evolution. doi: 10.1016/j.ympev.2003.11.009.

  • Irvine, S.Q., Carr, J.L., Bailey, W.J., Kawasaki, K., Shimizu, N., Amemiya, C.T., Ruddle, F.H., 2002. Genomic analysis of Hox clusters in the sea lamprey, Petromyzon marinus. Journal of Experimental Zoology (Molecular Development and Evolution) 294, 47–62.

    Article  CAS  Google Scholar 

  • Ishiguro, N.B., Miya, M., Nishida, M., 2003. Basal euteleostean relationships: a mitogenomic perspective on the phylogenetic reality of the “protacanthopterygii”. Molecular Phylogenetics and Evolution 27, 476–488.

    Article  PubMed  CAS  Google Scholar 

  • Ji, F.Y., Liu, J.D., Yi, M.S., Huang, L., Zhou, F., Yu, Q.X., 2002. Chromosomal localization of rice field eel Hox genes by PRINS. Yi Chuan Xue Bao (Acta Genetica Sinica) 29, 612–615 (in Chinese).

    CAS  Google Scholar 

  • Kim, C.B., Amemiya, C., Bailey, W., Kawasaki, K., Mezey, J., Miller, W., Minosima, S., Shimizu, N., Wagner, G.P., Ruddle, F., 2000. Hox cluster genomics in the horn shark, Heterodontus francisci. Proceedings of the National Academy of Sciences of the United States of America 97, 1655–1660.

    Article  PubMed  CAS  Google Scholar 

  • Koh, E.G.L., Lam, K., Christoffels, A., Erdmann, M.V., Brenner, S., Venkatesh, B., 2003. Hox gene clusters in the indonesian coelacanth, Latimeria menadoensis. Proceedings of the National Academy of Sciences of the United States of America 100, 1084–1088.

    Article  PubMed  CAS  Google Scholar 

  • Kurosawa, G., Yamada, K., Ishiguro, H., Hori, H., 1999. Hox gene complexity in medaka fish may be similar to that in pufferfish rather than zebrafish. Biochemical and Biophysical Research Communication 260, 66–70.

    Article  CAS  Google Scholar 

  • Larhammar, D., Lundin, L.G., H.F., 2002. The human Hox-bearing chromosome regions did arise by block or chromosome (or even genome) duplications. Genome Research 12, 1910–1920.

    Article  PubMed  CAS  Google Scholar 

  • Levine, E.M., Schechter, N., 1993. Homeobox genes expressed in the retina and brain of adult goldfish. Proceedings of the National Academy of Sciences of the United States of America 90, 2729–2733.

    Article  PubMed  CAS  Google Scholar 

  • Lynch, M., Conery, J.S., 2000. The evolutionary fate and consequences of duplicate genes. Science 290, 1151–1155.

    Article  PubMed  CAS  Google Scholar 

  • Lynch, V.J., Roth, J.J., Takahashi, K., Dunn, C., Nonaka, D., Stopper, G., Wagner, G.P., 2004. The origin of placental mammals is coincident with adaptive evolution of the developmental control genes HoxA-11 and HoxA-13. submitted.

  • Málaga-Trillo, E., Meyer, A., 2001. Genome duplications and accelerated evolution of Hox genes and cluster architecture in teleost fishes. American Zoologist 41, 676–686.

    Article  Google Scholar 

  • Martinez, P., Amemiya, C.T., 2002. Genomics of the HOX gene cluster. Comparative Biochemistry and Physiology Part B 133, 571–580.

    Article  Google Scholar 

  • McGinnis, W., Krumlauf, R., 1992. Homeobox genes and axial patterning. Cell 68, 283–302.

    Article  PubMed  CAS  Google Scholar 

  • Merrit, T.J.S., Quattro, J.M., 2001. Evidence for a period of directional selection following gene duplication in a neurally expressed locus of triosephosphate isomerase. Genetics 159, 689–697.

    Google Scholar 

  • Merrit, T.J.S., Quattro, J.M., 2003. Evolution of the vertebrate cytosolic malate dehydrogenase gene family: duplication and divergence in actinopterygian fish. Journal of Molecular Biology 56, 265–276.

    CAS  Google Scholar 

  • Meyer, A., Málaga-Trillo, E., 1999. More fishy tales about Hox gene clusters. Current Biology 9, R210–213.

    Article  PubMed  CAS  Google Scholar 

  • Meyer, A., 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. Current Opinion in Cell Biology 11, 699–704.

    Article  PubMed  CAS  Google Scholar 

  • Misof, B.Y., Blanco, M.J., Wagner, G.P., 1996. A PCR-survey of Hox genes of the zebrafish: new sequences and evolutionary implications. Journal of Experimental Biology 274, 193–206.

    CAS  Google Scholar 

  • Misof, B.Y., Wagner, G.P., 1996. Evidence for four Hox clusters in the killifish Fundulus heteroclitus (teleostei). Molecular Phylogenetics and Evolution 5, 309–322.

    Article  PubMed  CAS  Google Scholar 

  • Miya, M., Takeshima, H., Endo, H., Ishiguro, N.B., Inoue, J.G., Mukai, T., Satoh, T.P., Yamaguchi, M., Kawaguchi, A., Mabuchi, K., Shirai, S.M., Nishida, M., 2003. Major patterns of higher teleostean phylogenies: a new perspective based on 100 complete mitochondrial dna sequences. Molecular Phylogenetics and Evolution 26, 121–138.

    Article  PubMed  CAS  Google Scholar 

  • Mortlock, D.P., Sateesh, P., Innis, J.W., 2000. Evolution of N-terminal sequences of the vertebrate HOXA 13 protein. Mammalion Genome 11, 151–158.

    Article  CAS  Google Scholar 

  • Murray, B.W., Busby, E.R., Mommsen, T.P., Wright, P.A., 2003. Evolution of glutamine synthetase in vertebrates: multiple glutamine synthetase genes expressed in rainbow trout (Oncorhynchus mykiss). Journal of Experimental Biology 206, 1511–1521.

    Article  PubMed  CAS  Google Scholar 

  • Naruse, K., Fukamachi, S., Mitani, H., Kondo, M., Matsuoka, T., Kondo, S., Hanamura, N., Morita, Y., Hasegawa, K., Nishigaki, R., Shimada, A., Wada, H., Kusakabe, T., Suzuki, N., Kinoshita, M., Kanamori, A., Terado, T., Kimura, H., Nonaka, M., Shima, A., 2000. A detailed linkage map of medaka, Oryzias latipes: comparative genomics and genome evolution. Genetics 154, 1773–1784.

    PubMed  CAS  Google Scholar 

  • Ohno, S., 1970. Evolution by Gene Duplication. Springer, New York.

    Google Scholar 

  • Panopoulou, G., Hennig, S., Groth, D., Krause, A., Poustka, A.J., Herwig, R., Vingron, M., Lehrach, H., 2003. New evidence for genome-wide duplications at the origin of vertebrates using an amphioxus gene set and completed animal genomes. Genome Research 13, 1056–1066.

    Article  PubMed  Google Scholar 

  • Pavell, A.M., Stellway, E.J., 1994. Survey of Hox-like genes in the teleost Morone saxatilis: Implications for the evolution of the Hox gene family. Molecular Marine Biology and Biotechnology 3, 149–157.

    PubMed  CAS  Google Scholar 

  • Prohaska, S.J., Fried, C., Amemiya, C.T., Ruddle, F.H., Wagner, G.P., Stadler, P.F., 2004a. The shark HoxN cluster is homologous to the human HoxD cluster. Journal of Molecular Evolution in press.

  • Prohaska, S.J., Fried, C., Flamm, C., Wagner, G., Stadler, P.F., 2004b. Surveying phylogenetic footprints in large gene clusters: Applications to Hox cluster duplications. Molecular Phylogenetics and Evolution doi:10.1016/j.ympev.2003.08.009.

  • Robinson-Rechavi, M., Marchand, O., Escriva, H., Bardet, P.L., Zelus, D., Hughes, S., Laudet, V., 2001. Euteleost fish genomes are characterized by expansion of gene families. Genome Research 11, 781–788.

    Article  PubMed  CAS  Google Scholar 

  • Roest Crollius, H., Jaillon, O., Dasilva, C., Ozouf-Costaz, C., Fizames, C., Fischer, C., Bouneau, L., Billault, A., Quetier, F., Saurin, W., Bernot, A., Weissenbach, J., 2000. Characterization and repeat analysis of the compact genome of the freshwater pufferfish Tetraodon nigroviridis. Genome Research 10, 939–949.

    Article  PubMed  CAS  Google Scholar 

  • Ruddle, F.H., Bartels, J.L., Bentley, K.L., Kappen, C., Murta, M.T., Pendleton, J.W., 1994a. Evolution of Hox genes. Annual Review Genetics 28, 423–442.

    Article  CAS  Google Scholar 

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

    Google Scholar 

  • Saitou, N., Nei, M., 1987. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Molecular Biology and Evolution 4, 406–425.

    PubMed  CAS  Google Scholar 

  • Santini, S., Boore, J.L., Meyer, A., 2003. Evolutionary conservation of regulatory elements in vertebrate Hox gene clusters. Genome Research 13, 1111–1122.

    Article  PubMed  CAS  Google Scholar 

  • Scemama, J.-L., Hunter, M., McCallum, J., Prince, V., Stellwag, E., 2002. Evolutionary divergence of vertebrate Hoxb2 expression patterns and transcriptional regulatory loci. Journal of Experimental Zoology (Molecular Development and Evolution) 294, 285–299.

    Article  CAS  Google Scholar 

  • Schubert, F.R., Nieselt-Struwe, K., Gruss, P., 1993. The antennapedia-type homeobox genes have evolved from three precursors separated early in metazoan evolution. Proceedings of the National Academy of Sciences of the United States of America 90, 143–147.

    Article  PubMed  CAS  Google Scholar 

  • Shashikant, C.S., Utset, M.F., Violette, S.M., Wise, T.L., Einat, P., Einat, M., Pendleton, J.W., Schughart, K., Ruddie, F.H., 1991. Homeobox genes in mouse development. Critical Reviews in Eukaryotic Gene Expression 1, 207–245.

    PubMed  CAS  Google Scholar 

  • Simmons, M.P., Miya, M., 2004. Efficiently resolving the basal clades of a phylogenetic tree using Bayesian and parsimony approaches: a case study using mitogenomic data from 100 higher teleost fishes. Molecular Phylogenetics and Evolution, dol:10.1016/j.ympev.2003.08.004.

  • Snell, E.A., Scemama, J.L., Stellwag, E.J., 1999. Genomic organization of the Hoxa4-Hoxa10 region from Morone saxatilis: implications for Hox gene evolution among vertebrates. Journal of Experimental Zoology (Molecular Development and Evolution) 285, 41–49.

    Article  CAS  Google Scholar 

  • Stadler, H.S., Murray, J.C., Leysens, N.J., Goodfellow, P.J., Solursh, M., 1995. Phylogenetic conservation and physical mapping of members of the H6 homeobox gene family. Mammalian Genome 6, 383–388.

    Article  PubMed  CAS  Google Scholar 

  • Stadler, P.F., Fried, C., Prohaska, S.J., Bailey, W.J., Misof, B.Y., Ruddle, F.H., Wagner, G.P., 2004. Evidence for independent Hox gene duplications in the hagfish lineage: a PCR-based gene inventory of Eptatretus stoutii. Molecular Phylogenetics and Evolution, in press.

  • Stellwag, E.J., 1999. Hox gene duplications in fish. Cell Development and Biology 10, 531–540.

    Article  CAS  Google Scholar 

  • Stevens, C.J., Samallo, J., Schipper, H., Stroband, H.W., te Kronnie, G., 1996. Expression of Hoxb-1 during gastrulation and segmentation stages of carp (Cyprinus carpio). International Journal of Developmental Biology 40, 463–470.

    PubMed  CAS  Google Scholar 

  • Suzuki, T., Oohara, I., Kurokawa, T., 1998. Hoxd-4 expression during pharyngeal arch development in flounder (Paralichthys olivaceus) embryos and effects of retinoic acid on expression. Zoological Science 15, 57–67.

    Article  PubMed  CAS  Google Scholar 

  • Suzuki, T., Srinivastava, A.S., Kurokawa, T., 1999. Hoxb-5 is expressed in gill arch 5 during pharyngeal arch development of flounder Paralichthys olivaceus embryos. International Journal of Developmental Biology 43, 357–359.

    PubMed  CAS  Google Scholar 

  • Tagle, D.A., Koop, B.F., Goodman, M., Slightom, J.L., Hess, D.L., Jones, R.T., 1988. Embryonic epsilon and gamma globin genes of a prosimian primate (Galago crassicaudatus). Nucleotide and amino acid sequences, developmental regulation and phylogenetic footprints. Journal of Molecular Biology 203, 439–455.

    Article  PubMed  CAS  Google Scholar 

  • Takahashi, Y., Hamada, J.-I., Murakawa, K., Takada, M., Tada, M., Nogami, I., Hayashi, N., Nakamoric, S., Monden, M., Miyamoto, M., Katoh, H., Moriuchi, T., 2004. Expression profiles of 39 HOX genes in normal human adult organs and anaplastic thyroid cancer cell lines by quantitative realtime RT-PCR system. Experimental Cell Research 293, 144–153.

    Article  PubMed  CAS  Google Scholar 

  • Taylor, J., Braasch, I., Frickey, T., Meyer, A., Van De Peer, Y., 2003. Genome duplication, a trait shared by 22,000 species of ray-finned fish. Genome Research 13, 382–390.

    Article  PubMed  CAS  Google Scholar 

  • Van de Peer, Y., Taylor, J.S., Braasch, I., Meyer, A., 2001. The ghost of selection past: rates of evolution and functional divergence of anciently duplicated genes. Journal of Molecular Evolution 53, 436–446.

    Article  PubMed  Google Scholar 

  • Vandepoele, K., De Vos, W., Taylor, J.S., Meyer, A., Van de Peer, Y., 2004. Major events in the genome evolution of vertebrates: paranome age and size differ considerably between ray-finned fishes and land vertebrates. Proceedings of the National Academy of Sciences of the United States of America 101, 1638–1643.

    Article  PubMed  CAS  Google Scholar 

  • Wagner, G.P., Amemiya, C., Ruddle, F., 2003. Hox cluster duplication and the genetics of evolutionary novelties. Proceedings of the National Academy of Sciences of the United States of America 100, 14603–14606.

    Article  PubMed  CAS  Google Scholar 

  • Zardoya, R., Abouheif, E., Meyer, A., 1996. Evolutionary analyses of hedgehog and Hoxd-10 genes closely related to the zebrafish. Proceedings of the National Academy of Sciences of the United States of America 93, 13036–13041.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Sonja J. Prohaska.

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Prohaska, S.J., Stadler, P.F. The duplication of the Hox gene clusters in teleost fishes. Theory Biosci. 123, 89–110 (2004). https://doi.org/10.1016/j.thbio.2004.03.004

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