Mammalian Genome

, Volume 5, Issue 10, pp 633–639

Evolutionary conservation and genomic organization of XAP-4, an Xq28 located gene coding for a human rab GDP-dissociation inhibitor (GDI)

  • Z. Sedlacek
  • D. S. Konecki
  • B. Korn
  • S. M. Klauck
  • A. Poustka
Original Contributions

Abstract

After the development of efficient methods for the construction of transcription maps of defined genomic regions, the rate-limiting step in the analysis of the coding potentials of these regions is the elucidation of function of the novel genes and the examination of their possible involvement in hereditary diseases localized to the region. This can be greatly facilitated by the detection of sequence homology to a gene of known function. XAP-4 is one of the genes identified in the G6PD region of the human Xq28 by direct cDNA selection. The rapid assembly of this gene and the determination of its function was possible because of its sequence homology with the bovine smg p25A/rab3A GDP dissociation inhibitor (GDI). Sequence comparison with other GDIs in the databases has revealed that XAP-4 belongs to one of at least two distinct classes of mammalian rab GDIs. The rab GDIs, which play an important role in the regulation of cellular transport, are highly evolutionarily conserved, as are several other genes identified in the neighborhood of XAP-4. This genomic region is very gene dense, and all the cDNA clones from the approximately 2.5-kb-long transcript of XAP-4 map to a single 7.5-kb genomic EcoRI fragment. The genomic organization of XAP-4 has been examined to determine the distribution of the exonic sequences within this short segment of genomic DNA. It was found that, similar to several other genes from the region, XAP-4 is split into exons of average size, which are interrupted by very short introns.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Adams, M.D., Kelley, J.M., Gocayne, J.D., Dubnick, M., Polymeropoulos, M.H., Xiao, H., Merril, C.R., Wu, A., Olde, B., Moreno, R.F. (1991). Complementary DNA sequencing: expressed sequence tags and human genome project. Science 252, 1651–1656.Google Scholar
  2. Adams, M.D., Soares, M.B., Kerlavage, A.R., Fields, C., Venter, J.C. (1993a). Rapid cDNA sequencing (expressed sequence tags) from a directionally cloned human infant brain cDNA library. Nature Genet. 4, 373–380.Google Scholar
  3. Adams, M.D., Kerlavage, A.R., Fields, C., Venter, J.C. (1993b). 3400 new expressed sequence tags identify diversity of transcripts in human brain. Nature Genet. 4, 256–267Google Scholar
  4. Alcalay, M., Toniolo, D. (1988). CpG islands of the X chromosome are gene associated. Nucleic Acids Res. 16, 9527–9543.Google Scholar
  5. Asada, M., Kaibuchi, K., Takai, Y. (1993). EMBL Nucleotide Sequence Database, Acc. No. D13988.Google Scholar
  6. Bhat, K.S. (1992). EMBL Nucleotide Sequence Database, Acc. No. L05086.Google Scholar
  7. Bione, S., Tamanini, F., Maestrini, E., Triboli, C., Poustka, A., Torri, G., Rivella, S., Toniolo, D. (1993). Transcriptional organization of a 450kb region of the human X chromosome in Xq28. Proc. Natl. Acad. Sci. USA 90, 10977–10981.Google Scholar
  8. Boguski, M.S. (1993). GenBank, Acc. No. U00002.Google Scholar
  9. Brown, M.S., Goldstein, J.L. (1993). Mad Bet for Rab. Nature 366, 14–15.Google Scholar
  10. Buckler, A.J., Chang, D.D., Graw, S.L., Brook, D.J., Naber, D.A., Sharp, P.A., Houseman, D.E. (1991). Exon amplification: a strategy to isolate mammalian genes based on RNA splicing. Proc. Natl. Acad. Sci. USA 88, 4005–4009.Google Scholar
  11. Chen, E.Y., Cheng, A., Lee, A., Kuang, W.-J., Hillier, L.D., Green, P., Schlessinger, D., Ciccodicola, A., D'Urso, M. (1991). Sequence of human glucose-6-phosphate dehydrogenase cloned in plasmids and a yeast artificial chromosome. Genomics 10, 792–800.Google Scholar
  12. Coy, J.F., Kioschis, P., Sedlacek, Z., Poustka, A. (1994). Identification of tissue-specific expressed sequences in human band Xq28 using complex pig cDNA probes. Mamm. Genome, in press.Google Scholar
  13. Cremers, F.P.M., van de Pol, D.J.R., van Kerkhoff, L.P.M., Wieringa, B., Ropers, H.-H. (1990) Cloning of a gene that is rearranged in patients with choroideraemia. Nature 347, 674–677.Google Scholar
  14. Cremers, F.P.M., Molloy, C.M., Van de Pol, D.J.R., van den Hurk, J.A.J.M., Bach, I., van Kessel, A.H.M.G., Ropers, H.-H. (1992). An autosomal homologue of the choroideraemia gene colocalises with the Usher syndrome type II locus on the distal part of the chromosome 1q. Hum. Mol. Genet. 1, 71–75.Google Scholar
  15. Devereux, J., Haeberli, P., Smithies, O. (1984). A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 12, 387–395.Google Scholar
  16. Dowdy, S.F., Lai, K.-M., Weissman, B.E., Matsui, Y., Hogan, B.L.M., Stanbridge, E.J. (1991). The isolation and characterisation of a novel cDNA demonstrating an altered mRNA level in nontumorigenic Wilms' microcell hybrid cells. Nucleic Acids Res. 19, 5763–5769.Google Scholar
  17. Eisinger, D.P., Jiang, H.P., Serrero, G. (1993). A novel mouse gene highly conserved throughout evolution: regulation in adipocyte differentiation and in tumorigenic cell lines. Biochem. Biophys. Res. Commun. 196, 1227–1232.Google Scholar
  18. Filippi, M., Triboli, C., Toniolo, D. (1990). Linkage and sequence conservation of the X-linked genes DXS253E (P3) and DXS254E (GdX) in mouse and man. Genomics 7, 453–457.Google Scholar
  19. Fodor, E., Lee, R.T., O'Donnell, J.J. (1991). Analysis of choroideraemia gene. Nature 351, 614.Google Scholar
  20. Fujioka, H., Kikuchi, A., Yoshida, Y., Kuroda, S., Takai, Y. (1990). A small GTP-binding protein (G-protein) recognised by smg p25A GDP dissociation inhibitor (GDI) in human platelet membranes and GDI for this small G-protein in human platelet cytosol. Biochem. Biophys. Res. Commun. 168, 1244–1252.Google Scholar
  21. Garrett, M.D., Kabcenell, A.K., Zahner, J.E., Kaibuchi, K., Sasaki, T., Takai, Y., Cheney, C.M., Novick, P.J. (1993). Interaction of Sec4 with GDI proteins from bovine brain, Drosophila melanogaster and Saccharomyces cerevisiae. FEBS Lett. 331, 233–238.Google Scholar
  22. Hawkins, J.D. (1988). A survey on intron and exon lengths. Nucleic Acids Res. 16, 9893–9908.Google Scholar
  23. Higgins, D.G., Sharp, P.M. (1988). CLUSTAL: a package for performing multiple sequence alignment on a microcomputer. Gene 73, 237–244.Google Scholar
  24. Khan, A.S., Wilcox, A.S., Polymeropoulos, M.H., Hopkins, J.A., Stevens, T.J., Robinson, M., Orpana, A.K., Sikela, J.M., (1993). Single pass sequencing and physical and genetic mapping of human brain cDNAs. Nature Genet 2, 180–185.Google Scholar
  25. Korn, B., Sedlacek, Z., Manca, A., Kioschis, P., Konecki, D., Lehrach, H., Poustka, A. (1992). A strategy for the selection of transcribed sequences in the Xq28 region. Hum. Mol. Genet. 1, 235–242Google Scholar
  26. Kozak, M. (1987). An analysis of 5′ noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 15, 8125–8148.Google Scholar
  27. Leffers, H., Nielsen, M.S., Andersen, A., Honoré, B., Madsen, P., Vanderkerchove, J., Celis, J.E. (1993). Identification of two human rho GDP dissociation inhibitor proteins whose overexpression leads to disruption of the actin cytoskeleton. Exp. Cell Res. 209, 165–174.Google Scholar
  28. Lovett, M., Kere, J., Hinton, L.M. (1991). Direct selection: a method for the isolation of cDNAs encoded by large genomic regions. Proc. Natl. Acad. Sci. USA 88, 9628–9632.Google Scholar
  29. Matsui, Y., Kikuchi, A., Araki, S., Hata, Y., Kondo, J., Teranishi, Y., Takai, Y. (1990). Molecular cloning and characterisation of a novel type of regulatory protein (GDI) for smg p25A, a ras p21-like GTP-binding protein. Mol. Cell. Biol. 10, 4116–4122.Google Scholar
  30. Merry, D.E., Jänne, P.A., Landers, J.E., Lewis, R.A., Nussbaum, R.L. (1992). Isolation of a candidate gene for choroideraemia. Proc. Natl. Acad. Sci. USA 89, 2135–2139.Google Scholar
  31. Nishimura, N. (1993). EMBL Nucleotide Sequence Database, Acc. Nos. X74401, X74402.Google Scholar
  32. Parimoo, S., Patanjali, S.R., Shukla, H., Chaplin, D.D., Weissman, S.M. (1991). cDNA selection: efficient PCR approach for the selection of cDNAs encoded in large chromosomal DNA fragments. Proc. Natl. Acad. Sci. USA 88, 9623–9627.Google Scholar
  33. Pearson, W.R., Lipman, D.J. (1988). Improved tools for biological sequence comparison. Proc. Natl. Acad. Sci. USA 85, 2444–2448.Google Scholar
  34. Persico, M.G., Viglietto, G., Martini, G., Toniolo, D., Paonessa, G., Moscatelli, C., Dono, R., Vulliamy, T., Luzzato, L., D'Urso, M. (1968). Isolation of human glucose-6-phosphate dehydrogenase (G6PD) cDNA clones: primary structure of the protein and unusual 5′ non-coding region. Nucleic Acids Res. 14, 2511–2522.Google Scholar
  35. Sedlacek, Z., Korn, B., Konecki, D.S., Siebenhaar, R., Coy, J.F., Kioschis, P. Poustka, A. (1993a). Construction of a transcription map of a 300kb region around the human G6PD locus by direct cDNA selection. Hum. Mol. Genet. 2, 1865–1869.Google Scholar
  36. Sedlacek, Z., Konecki, D.S., Siebenhaar, R., Kioschis, P., Poustka, A. (1993b). Direct selection of DNA sequences conserved betwen species. Nucleic Acids Res. 21, 3419–3425.Google Scholar
  37. Shapiro, M.B., Senapathy, P. (1987). RNA splice junctions of different classes of eukaryotes: sequence statisties and functional implications in gene expression. Nucleic Acids Res. 15, 7155–7174.Google Scholar
  38. Simons, K., Zerial, M. (1993). Rab proteins and the road maps for intracellular transport. Neuron 11, 789–799.Google Scholar
  39. Toniolo, D., Persico, M., Alcalay, M. (1988). A housekeeping gene on the X chromosome encodes a protein similar to ubiquitin. Proc. Natl. Acad. Sci. USA 85, 851–855.Google Scholar
  40. Uberbacher, E.C., Mural, R.J. (1991). Locating protein-coding regions in human DNA sequences by a multiple sensor-neural network approach. Proc. Natl. Acad. Sci. USA 88, 11261–11265.Google Scholar
  41. Ueda, T., Takeyama, Y., Ohmori, Y., Ohyanagi, H., Saitoh, Y., Takai, Y. (1991). Purification and characterisation from rat liver cytosol of a GDP dissociation inhibitor (GDI) for liver 24KG, a ras p21-like GTP-binding protein, with properties similar to those of smg p25A GDI. Biochemistry 30, 909–917.Google Scholar
  42. Ullrich, O., Stenmark, H., Alexandrov, K., Huber, L.A., Kaibuchi, K., Sasaki, T., Takai, Y., Zerial, M. (1993). Rab GDP dissociation inhibitor as a general regulator for the membrane association of rab proteins. J. Biol. Chem. 268, 18143–18150.Google Scholar
  43. van den Ouweland, A.M.W., Kioschis, P., Verdijk, M., Tamanini, F., Toniolo, D., Poustka, A., van Oost, B.A. (1992). Identification and characterisation of a new gene in the human Xq28 region. Hum. Mol. Genet. 1, 269–273.Google Scholar
  44. Waldherr, M., Ragnini, A., Schweyen, R.J., Boguski, M.S. (1993). MRS6-yeast homologue of the choroideraemia gene. Nature Genet. 3, 193–194.Google Scholar
  45. Yuzo, M., Takuji, S. (1993). EMBL Nucleotide Sequence Database, Acc. No. D25063.Google Scholar
  46. Zahner, J.E., Cheney, C.M. (1993). A drosophila homolog of bovine smg p25A GDP dissociation inhibitor undergoes a shift in isoelectric point in the developmental mutant quartet. Mol. Cell. Biol. 13, 217–227.Google Scholar

Copyright information

© Springer-Verlag New York Inc. 1994

Authors and Affiliations

  • Z. Sedlacek
    • 1
  • D. S. Konecki
    • 1
  • B. Korn
    • 1
  • S. M. Klauck
    • 1
  • A. Poustka
    • 1
  1. 1.Deutsches KrebsforschungszentrumHeidelbergGermany

Personalised recommendations