Advertisement

Searching for Regulatory Elements of Alternative Splicing Events Using Phylogenetic Footprinting

  • Daichi Shigemizu
  • Osamu Maruyama
Part of the Lecture Notes in Computer Science book series (LNCS, volume 3240)

Abstract

We consider the problem of finding candidates for regulatory elements of alternative splicing events from orthologous genes, using phylogenetic footprinting. The problem is formulated as follows: We are given orthologous sequences P 1,...,P a and N 1,...,N b from a + b different species, and a phylogenetic tree relating these species. Assume that for i=1,...,a, P i is known to have some alternative splicing events, although N j does not have any alternative splicing events. Our objective is to find all sets of substrings s 1,...,s a of P 1,...,P a such that s 1,...,s a are similar to each other to some extent, and such that any substrings of N 1,...,N b are not similar to s 1,...,s a . To this aim, we have modified the phylogenetic footprinting algorithm given by Blanchette et al. to solve our problem. We report the results of our preliminary computational experiments on several sets of orthologous genes of the five species, H.sapiens, M.musculus, D.melanogaster, C.elegans, and A.thaliana. It is interesting that many of the substrings selected by our algorithm from the coding sequences of H.sapiens are substrings in the intronic sequences flanking the alternatively spliced exons of the coding sequence. This result implies that regulatory elements of alternative splicing events would be located in intronic sequences flanking the alternatively spliced exons.

Keywords

Alternative Splice Regulatory Element Orthologous Gene Intronic Sequence Dynamic Programming Algorithm 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Brudno, M., Gelfand, M., Spengler, S., Zorn, M., Dubchak, I., Conboy, J.G.: Computational analysis of candidate intron regulatory elements for tissue-specific alternative pre-mRNA splicing. Nucl. Acids Res. 29, 2338–2348 (2001)CrossRefGoogle Scholar
  2. 2.
    Sakai, H., Maruyama, O.: Extensive search for discriminative features of alternative splicing. In: Pacific Symposium on Biocomputing, vol. 9, pp. 54–65 (2004)Google Scholar
  3. 3.
    Zheng, C., Nair, T., Gribskov, M., Kwon, Y., Li, H., Fu, X.D.: A database designed to computationally aid an experimental approach to alternative splicing. In: Pacific Symposium on Biocomputing, vol. 9, pp. 78–88 (2004)Google Scholar
  4. 4.
    Dralyuk, I., Brudno, M., Gelfand, M., Zorn, M., Dubchak, I.: ASDB: database of alternatively spliced genes. Nucl. Acids Res. 28, 296–297 (2000)CrossRefGoogle Scholar
  5. 5.
    Ji, H., Zhou, Q., Wen, F., Xia, H., Lu, X., Li, Y.: AsMamDB: an alternative splice database of mammals. Nucl. Acids Res. 29, 260–263 (2001)CrossRefGoogle Scholar
  6. 6.
    Burset, M., Solovyev, I.S.V.: SpliceDB: database of canonical and non-canonical mammalian splice sites. Nucl. Acids Res. 29, 255–259 (2001)CrossRefGoogle Scholar
  7. 7.
    Brett, D., Hanke, J., Lehmann, G., Haase, S., Delbruck, S., Krueger, S., Bork, J.R.P.: EST comparison indicates 38% of human mRNAs contain possible alternative splice forms. FEBS Lett. 474, 83–86 (2000)CrossRefzbMATHGoogle Scholar
  8. 8.
    Croft, L., Schandorff, S., Clark, F., Burrage, K., Arctander, P., Mattick, J.: ISIS, the intron information system, reveals the high frequency of alternative splicing in the human genome. Nat. Genet. 24, 340–341 (2000)CrossRefGoogle Scholar
  9. 9.
    Lee, C., Atanelov, L., Modrek, B., Xing, Y.: ASAP: the alternative splicing annotation project. Nucl. Acids Res. 31, 101–105 (2003)CrossRefGoogle Scholar
  10. 10.
    Blanchette, M., Schwikowski, B., Tompa, M.: Algorithms for phylogenetic footprinting. J. Comput. Biol. 9, 211–223 (2002)CrossRefGoogle Scholar
  11. 11.
    Blanchette, M., Tompa, M.: FootPrinter: a program designed for phylogenetic footprinting. Nucl. Acids Res. 31, 3840–3842 (2003)CrossRefGoogle Scholar
  12. 12.
    Tagle, D., Koop, B., Slightom, M.G.J., Hess, D., Jones, R.: Embryonic epsilon and gamma globin genes of a prosimian primate (Galago crassicaudatus) nucleotide and amino acid sequences, developmental regulation and phylogenetic footprints. J. Mol. Biol. 203, 439–455 (1988)CrossRefGoogle Scholar
  13. 13.
    Sorek, R., Ast, G.: Intronic sequences flanking alternatively spliced exons are conserved between human and mouse. Genome Research 13, 1631–1637 (2003)CrossRefGoogle Scholar
  14. 14.
    Thompson, J., Higgins, D., Gibson, T.: CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, positionsspecific gap penalties and weight matrix choice. Nucl. Acids Res. 22, 4673–4680 (1994)CrossRefGoogle Scholar
  15. 15.
    Remm, M., Storm, C., Sonnhammer, E.: Automatic clustering of orthologs and in-paralogs from pairwise species comparisons. J. Mol. Biol. 314, 1041–1052 (2001)CrossRefGoogle Scholar
  16. 16.
    Birney, E., Andrews, D., Bevan, P., Caccamo, M., Cameron, G., Chen, Y., Clarke, L., Coates, G., Cox, T., Cuff, J., Curwen, V., Cutts, T., Down, T., Durbin, R., Eyras, E., Fernandez-Suarez, X.M., Gane, P., Gibbins, B., Gilbert, J., Hammond, M., Hotz, H., Iyer, V., Kahari, A., Jekosch, K., Kasprzyk, A., Keefe, D., Keenan, S., Lehvaslaiho, H., McVicker, G., Melsopp, C., Meidl, P., Mongin, E., Pettett, R., Potter, S., Proctor, G., Rae, M., Searle, S., Slater, G., Smedley, D., Smith, J., Spooner, W., Stabenau, A., Stalker, J., Storey, R., Ureta-Vidal, A., Woodwark, C., Clamp, M., Hubbard, T.: Ensembl 2004. Nucl. Acids Res., D468–D470 (2004)Google Scholar
  17. 17.
    Apweiler, R., Bairoch, A., Wu, C., Barker, W., Boeckmann, B., Ferro, S., Gasteiger, E., Huang, H., Lopez, R., Magrane, M., Martin, M., Natale, D., Yeh, C.O.N.R.L.: UniProt: the universal protein knowledgebase. Nucl. Acids Res. 32, D115– D119 (2004)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2004

Authors and Affiliations

  • Daichi Shigemizu
    • 1
  • Osamu Maruyama
    • 2
  1. 1.Graduate School of Systems Life SciencesKyushu UniversityFukuokaJapan
  2. 2.Faculty of MathematicsKyushu UniversityFukuokaJapan

Personalised recommendations