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Part of the book series: Contemporary Issues in Genetics and Evolution ((CIGE,volume 10))

Abstract

Introns are integral elements of eukaryotic genomes that perform various important functions and actively partici- pate in gene evolution. We review six distinct roles of spliceosomal introns: (1) sources of non-coding RNA; (2) carriers of transcription regulatory elements; (3) actors in alternative and trans-splicing; (4) enhancers of meiotic crossing over within coding sequences; (5) substrates for exon shuffling; and (6) signals for mRNA export from the nucleus and nonsense-mediated decay. We consider transposable capacities of introns and the current state of the long-lasting debate on the ‘:early-or-late’ origin of introns. Cumulative data on known types of contemporary exon shuffling and the estimation of the size of the underlying exon universe are also discussed. We argue that the processes central to introns-early (exon shuffling) and introns-late (intron insertion) theories are entirely compat- ible. Each has provided insight: the latter through elucidating the transposon capabilities of introns, and the former through understanding the importance of introns in genomic recombination leading to gene rearrangements and evolution.

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References

  • Akamatsu, W. & H. Okano, 2001. No to Hattatsu. Brain Dev. 33: 114–120.

    CAS  Google Scholar 

  • Akopian, A.N., K. Okuse, V. Souslova, S. England, N. Ogata & J.N. Wood, 1999. Trans-splicing of a voltage-gated sodium channel is regulated by nerve growth factor. FEBS Lett. 445: 177–182.

    Article  PubMed  CAS  Google Scholar 

  • Aoki, Y., Z. Huang, S.S. Thomas, P.G. Bhide, I. Huang, M.A. Moskowitz & S.A. Reeves, 2000. Increased susceptibility to ishemia-induced brain damage in transgenic mice over-expressing a dominant negative form of SHP2. FASEB J. 14: 1965–1973.

    Article  PubMed  CAS  Google Scholar 

  • Beiford, M. & P.S. Perlman, 1995. Mechanisms of intron mobility. J. Biol. Chem. 270: 30237–30240.

    Article  Google Scholar 

  • Berget, S.M., C. Moore & P.A. Sharp, 1977. Spliced segments at the 5′terminus of adenovirus 2 late mRNA. Proc. Natl. Acad. Sci. USA 74: 3171–3175.

    Article  PubMed  CAS  Google Scholar 

  • Black, D.L., 2000. Protein diversity from alternative splicing: a challenge for bioinformatics and post-genome biology. Cell 103: 367–370.

    Article  PubMed  CAS  Google Scholar 

  • Blake, C.C.R, 1978. Do genes-in-pieces imply proteins-in-pieces? Nature 273: 267.

    Article  Google Scholar 

  • Bonen, L. & J. Vogel, 2001. The ins and outs of group II introns. Trends Genet. 17: 322–331.

    Article  PubMed  CAS  Google Scholar 

  • Brooks, A.R., B.R Nagy, S. Taylor, W.S. Simonet, J.M. Taylor & B. Levy-Wilson, 1994. Sequences containing the second-intron enhancer are essential for transcription of the human apolipoprotein B gene in the livers of transgenic mice. Mol. Cell. Biol. 14: 2243–2256.

    Article  PubMed  CAS  Google Scholar 

  • Carvalho, A.B. & A.G. Clark, 1999. Intron size and natural selection. Nature 401: 344.

    Article  PubMed  CAS  Google Scholar 

  • Caudevilla, C, C. Codony, D. Serra, G. Plasencia, R. Roman, A. Graessmann, G. Asins, M. Bach-Elias & F.G. Hegardt, 2001, Localization of an exonic splicing enhancer responsible for mammalian natural trans-splicing. Nucl. Acids Res. 29: 3108–3115.

    Article  PubMed  CAS  Google Scholar 

  • Cavaille, J., K. Buiting, M. Kiefmann, M. Lalande, C.I. Brannan, B. Horsthemke, J.-P. Bachellerie, J. Brosius & A. Huttenhofer, 2000. Identification of brain-specific and imprinted small nucleolar RNA genes exhibiting an unusual genomic organization. Proc. Natl. Acad. Sci. USA 97: 14311–14316.

    Article  PubMed  CAS  Google Scholar 

  • Cavalier-Smith, T., 1985. Selfish DNA and the origin of introns. Nature 315: 283–284.

    Article  PubMed  CAS  Google Scholar 

  • Cavalier-Smith, T., 1991. Intron phylogeny: a new hypothesis. Trend. Genet. 7: 145–148.

    Article  CAS  Google Scholar 

  • Chow, L.T., R.E. Gelinas, J.R. Broker & R.J. Roberts, 1977. An amazing sequence arrangement at the 5′ends of adenovirus 2 messenger RNA. Cell 12: 1–8.

    Article  PubMed  CAS  Google Scholar 

  • Comeron, J.M. & M. Kreitman, 2000. The correlation between intron length and recombination in Drosophila: dynamic equilibrium between mutational and selective forces. Genetics 156: 1175–1190.

    PubMed  CAS  Google Scholar 

  • Crick, F., 1979. Split genes and RNA splicing. Science 204: 264–271.

    Article  PubMed  CAS  Google Scholar 

  • Croft, L., S. Schandroff, F. Clark, K. Burrage, P. Arctander & J.S. Mattick, 2000. ISIS, the intron information system, reveals the high frequency of alternative splicing in the human genome. Nat. Genet. 24: 340–341.

    Article  PubMed  CAS  Google Scholar 

  • Darnel, J.E., 1978. Implications of RNA. RNA splicing in evolution of eukaryotic cells. Science 202: 1257–1260.

    Article  Google Scholar 

  • Domon, C. & A. Steinmetz, 1994. Exon shuffling in anther-specific genes from sunflower. Mol. Gen. Genet. 244: 312–317.

    Article  PubMed  CAS  Google Scholar 

  • Doolittle, W.F., 1978. Genes in pieces: were they ever together? Nature 272: 581–582.

    Article  Google Scholar 

  • Doolittle, W.F., 1999. Lateral genomics. Trends Cell Biol. 9: M5–M8.

    Article  PubMed  CAS  Google Scholar 

  • Dorit, R.L., L. Schoengach & W. Gilbert, 1990. How big is the universe of exons? Science 250: 1377–1382.

    Article  PubMed  CAS  Google Scholar 

  • Dorn, R., G. Reuter & A. Loewendorf, 2001. Transgene analysis proves mRNA trans-splicing at the complex mod(mdg4) locus in Drosophila. Proc. Natl. Acad. Sci. USA 98: 9724–9729.

    Article  PubMed  CAS  Google Scholar 

  • Douglas, S., S. Zauner, M. Fraunholz, M. Beaton, S. Penny, L.T. Deng, X. Wu, M. Reith, T. Cavalier-Smith & U.G. Maier, 2001. The highly reduced genome of an enslaved algal nucleus. Nature 410: 1091–1096.

    Article  PubMed  CAS  Google Scholar 

  • Eddy, S.R., 1999. Noncoding RNA genes. Curr. Opin. Genet. Dev. 9: 695–699.

    Article  PubMed  CAS  Google Scholar 

  • Evans, D. & T. Blumenthal, 2000. Trans splicing of polycistronic Caenorhabditis elegans pre-mRNAs: analysis of the SL2 RNA. Mol. Cell. Biol. 20: 6659–6667.

    Article  PubMed  CAS  Google Scholar 

  • Fast, N.M., A.J. Roger, C.A. Richardson & W.F. Doolittle, 1998. U2 and U6 snRNA genes in the microsporidian Nosema locustae: evidence for a functional spliceosome. Nucl. Acids Res. 26: 3202–3207.

    Article  PubMed  CAS  Google Scholar 

  • Fast, N.M. & W.F. Doolittle, 1999. Trichomonas vaginalis possesses a gene encoding the essential spliceosomal component, PRP8.

    Google Scholar 

  • Fedorov, A., G. Suboch, M. Bujakov & L. Fedorova, 1992. Analysis of nonuniformity in intron phase distribution. Nucl. Acids Res. 20: 2553–2557.

    Article  PubMed  CAS  Google Scholar 

  • Fedorov, A., V. Starshenko, L. Fedorova, V. Filatov & E. Grigor’ev, 1998. Influence of exon duplication and shuffling on intron phase distribution. J. Mol. Evol. 46: 263–271.

    Article  PubMed  CAS  Google Scholar 

  • Ferguson, K.C. & J.H. Rothman, 1999. Alterations in the conserved SL1 trans-spliced leader of Caenorhabditis elegans demonstrate flexibility in length and sequence requirements in vivo. Mol. Cell. Biol. 19: 1892–1900.

    PubMed  CAS  Google Scholar 

  • Filipowicz, W., 2000. Imprinted expression of small nucleolar RNAs in brain: time for RNomics. Proc. Natl. Acad. Sci. USA 97: 14035–14037.

    Article  PubMed  CAS  Google Scholar 

  • Gilbert, W, 1978. Why genes in pieces? Nature 271: 501.

    Article  PubMed  CAS  Google Scholar 

  • Gilbert, W., 1987. The exon theory of genes. Cold Spring Harbor Symp. Quant. Biol. 52: 901–905.

    Article  CAS  Google Scholar 

  • Giroux, M.J., M. Clancy, J. Baier, L. Ingham, D. McCarty & C. Hannah, 1994. De novo synthesis of an intron by the maize transposable element Dissociation. Proc. Natl. Acad. Sci. USA 91: 12150–12154.

    Article  PubMed  CAS  Google Scholar 

  • Hartman, H. & A. Fedorov, 2002. The origin of the eukaryotic cell-a genomic investigation. Proc. Natl. Acad. Sci. USA, 99: 1420–1425.

    Article  PubMed  CAS  Google Scholar 

  • Hogenesch, J.B., K.A. Ching, S. Batalov, A.I. Su, J.R. Walker, Y.S.A. Zhou, Kay, R.G. Schultz & M.R Cooke, 2001. A comparison of the Celera and Ensembl predicted gene sets reveals little overlap in novel genes. Cell 106: 413–415.

    Article  PubMed  CAS  Google Scholar 

  • Howell, M. & C.S. Hill, 1997. Xsmad2 directly activates the activininducible, dorsal mesoderm gene XFKH1 in Xenopus embryos. EMBOJ. 16:7411–7421.

    Article  CAS  Google Scholar 

  • Hural, J.A., M. Kwan, G. Henkel, M.B. Hock & M.A. Brown, 2000. An intron transcriptional enhancer element regulates IL-4 gene locus accessibility in mast cells. J. Immunol. 165: 3239–3249.

    PubMed  CAS  Google Scholar 

  • Jeffreys, A.J. & R.A. Flavell, 1977. The rabbit beta-globin gene contains a large insert in the coding sequence. Cell 12: 1097–1108.

    Article  PubMed  CAS  Google Scholar 

  • Katinka, M.D., S. Duprat, E. Cornillot, G. Metenier, F. Thomarat, G. Prensier, V. Barbe, E. Peyretaillade, P. Brottier, P. Wincker, E. Delbac, H. El Alaoui, P. Peyret, W. Saurin, M. Gouy, J. Weissenbach & C.P. Vivares, 2001. Genome sequence and gene compaction of the eukaryote parasite Encephalitozoon cuniculi. Nature 414: 450–453.

    Article  PubMed  CAS  Google Scholar 

  • Kawasaki, T., S. Okumura, N. Kishimoto, H. Shimada & H. Ichikawa, 1999. RNA maturation of the rice SPK gene may involve trans-splicing. Plant J. 18: 625–632.

    Article  PubMed  CAS  Google Scholar 

  • Krause, M. & D. Hirsh, 1987. A trans-spliced leader sequence on actin mRNA in C. elegans. Cell 49: 753–761.

    Article  PubMed  CAS  Google Scholar 

  • Lambowitz, A.M. & M. Belford, 1993. Introns as mobile genetic elements. Annu. Rev. Biochem. 62: 587–622.

    Article  PubMed  CAS  Google Scholar 

  • Liu, J. & E.S. Maxwell, 1990. Mouse U14 snRNA is encoded in an intron of the mouse cognate hsc70 heat shock gene. Nucl. Acids Res. 18, 6565–6571.

    Article  PubMed  CAS  Google Scholar 

  • Logsdon, J.M., M.G. Tyshenko, C. Dixon, J.D. Jafari, V.K. Walker & J.D. Palmer, 1995. Seven newly discovered intron positions in the triose-phosphate isomerase gene: evidence for the intronslate theory. Proc. Natl. Acad. Sci. USA 92: 8507–8511.

    Article  PubMed  CAS  Google Scholar 

  • Logsdon, J.M., 1998. The recent origin of spliceosomal introns revised. Curr. Opin. Genet. Dev. 8: 637–648.

    Article  PubMed  CAS  Google Scholar 

  • Logsdon, J.M., A. Stoltzfus & W.F. Doolittle, 1998. Molecular evolution: recent cases of spliceosomal intron gain? Curr. Biol. 8: R560–R563.

    Article  PubMed  CAS  Google Scholar 

  • Long, M. & C.H. Langley, 1993. Natural selection and the origin of jingwei, a chimeric processed functional gene in Drosophila. Science 260: 91–95.

    Article  PubMed  CAS  Google Scholar 

  • Long, M., C. Rosenberg & W. Gilbert, 1995. Intron phase correlations and the evolution of the intron-exon structure of genes. Proc. Natl. Acad. Sci. USA 92: 12495–12499.

    Article  PubMed  CAS  Google Scholar 

  • Long, M., W. Wang & J. Zhang, 1999. Origin of new genes and source for N-terminal domain of the chimerical gene, jingwei in Drosophila. Gene 238: 135–141.

    Article  PubMed  CAS  Google Scholar 

  • Long, M. & C. Rosenberg, 2000. Testing the ‘:proto-splice sites’ model of intron origin: evidence from analysis of intron phase correlations. Mol. Biol. Evol. 17: 1789–1796.

    Article  PubMed  CAS  Google Scholar 

  • Long, M., 2001. Evolution of novel genes. Curr. Opin. Genet. Dev. 11:673–680.

    Article  PubMed  CAS  Google Scholar 

  • Lopez, A.J., 1998. Alternative splicing of pre-mRNA: development consequences and mechanisms of regulation. Annu. Rev. Genet. 32: 279–305.

    Article  PubMed  CAS  Google Scholar 

  • Lothian, C. & U. Lendahl, 1997. An evolutionary conserved region in the second intron of the human nestin gene directs gene expression to CNS progenitor cells and to early neural crest cells. Eur. J. Neurosci. 9: 452–462.

    Article  PubMed  CAS  Google Scholar 

  • Lou, H., R.F. Gagel & S.M. Berget, 1996. An intron enhancer recognized by splicing factors activates polyadenylation. Genes Dev. 10: 208–219.

    Article  PubMed  CAS  Google Scholar 

  • Maniatis, T. & R. Reed, 2002. An extensive network of coupling among gene expression machines. Nature 416: 499–506.

    Article  PubMed  CAS  Google Scholar 

  • Martinez-Abarca, F. & N. Toro, 2000. Group II introns in the bacterial world. Mol. Microbiol. 38: 917–926.

    Article  PubMed  CAS  Google Scholar 

  • Maxwell, E.S. & M.J. Fournier, 1995. The small nucleolar RNAs. Ann. Rev. Biochem. 35: 897–934.

    Article  Google Scholar 

  • Missler, M. & T.C. Sudhof, 1998. Neuroxins: three genes and 1001 products. Trends Genet. 14: 20–26.

    Article  PubMed  CAS  Google Scholar 

  • Mitchell, J.R. & K. Collins, 2000. Human telomerase activation requires two independent interactions between telomerase RNA and telomerase reverse transcriptase. Mol. Cell 6: 361–371.

    Article  PubMed  CAS  Google Scholar 

  • Muscarella, D.E. & V.M. Vogt, 1989. A mobile group I intron in the nuclear rDNA of Physarum polycephalum. Cell 56: 443–454.

    Article  PubMed  CAS  Google Scholar 

  • Nikoh, N. & T. Fukatsu, 2001. Evolutionary dynamics of multiple group I introns in nuclear ribosomal RNA genes of endoparasitic fungi of the genus Cordyceps. Mol. Biol. Evol. 81: 1631–1642.

    Article  Google Scholar 

  • Nilsen, T.W., 2001. Evolutionary origin of SL-addition trans-splicing: still an enigma. Trends Genet. 17: 678–680.

    Article  PubMed  CAS  Google Scholar 

  • Nixon, J.E.J., A. Wang, H.G. Morrison, A.G. McArthur, M.L. Sogin, B.J. Loftus & J. Samuelson, 2002. A Spliceosomal intron in Giardia lamblia. Proc. Natl. Acad. Sci. USA 99: 3701–3705.

    Article  PubMed  CAS  Google Scholar 

  • Nurminsky, D.I., M.V. Nurminskaya, D. DeAguiar & D.L. Hartl, 1998. Selective sweep of a newly evolved sperm-specific gene in Drosophila. Nature 396: 572–575.

    Article  PubMed  CAS  Google Scholar 

  • Oshima, R.G., L. Abrams & D. Kulesh, 1990. Activation of an intron enhancer within the keratin 18 gene by expression of c-fos and c-jun in undifferentiated F9 embryonal carcinoma cells. Genes Dev. 4: 835–848.

    Article  PubMed  CAS  Google Scholar 

  • Palmer, J.D. & J.M. Logsdon, 1991. The recent origin of introns. Curr. Opin. Genet. Dev. 1: 470–477.

    Article  PubMed  CAS  Google Scholar 

  • Pan, Q. & R.U. Simpson, 1999. C-myc intron element-binding proteins are required for 1,25-dihydroxyvitamin D3 regulation of c-myc during HL-60 cell differentiation and the involvement of HOXB4. J. Biol. Chem. 274: 8437–8444.

    Article  PubMed  CAS  Google Scholar 

  • Pankov, R., A. Umezawa, R. Maki, C.J. Der, C.A. Hauser & R.G. Oshima, 1994. Oncogene activation of human keratin 18 transcription via the Ras signal transduction pathway. Proc. Natl. Acad. Sci. USA 91: 873–877.

    Article  PubMed  CAS  Google Scholar 

  • Patthy, L., 1999. Genome evolution and the evolution of exonshuffling-a review. Gene 238: 103–114.

    Article  PubMed  CAS  Google Scholar 

  • Peculis, B.A., 2000. RNA-binding proteins: if it looks like a sn(o)RNA. Curr. Biol. 10: R916–R918.

    Article  PubMed  CAS  Google Scholar 

  • Peng, Y., A. Genin, N.B. Spinner, R.H. Diamond & R. Taub, 1998. The gene encoding human nuclear protein tyrosine phosphatase, PRL-1. Cloning, chromosomal localization and identification of an intron enhancer. J. Biol. Chem. 273: 17286–17295.

    Article  PubMed  CAS  Google Scholar 

  • Pogacic, V, F. Dragon & W. Filipowicz, 2000. Human H/ACA small nucleolar RNPs and telomerase share evolutionarily conserved proteins NHP2 and NOP10. Mol. Cell. Biol. 20: 9028–9040.

    Article  PubMed  CAS  Google Scholar 

  • Reed, R. & K. Magni, 2001. A new view of mRNA export: separating the wheat from the chaff. Nat. Cell Biol. 3: E201–E204.

    Article  PubMed  CAS  Google Scholar 

  • Rhodes, K. & R.G. Oshima, 1998. A regulatory element of the human keratin 18 gene with AP-1-dependent promoter activity. J. Biol. Chem. 273: 26534–26542.

    Article  PubMed  CAS  Google Scholar 

  • Roger, A.J. & W.F. Doolittle, 1993. Why introns-in-pieces? Nature 364: 289–290.

    Google Scholar 

  • Saxonov, S. & W. Gilbert, 2003. The universe of exons revisited. Genetica 118:267–278.

    Article  PubMed  CAS  Google Scholar 

  • Schmucker, D., J. Clemens, J. Shu, C. Worby, J. Xiao, M. Muda, J. Dixon & L. Zipursky, 2000. Drosophila Dscam is an axon guidance receptor exhibiting extraordinary molecular diversity. Cell 101:671–684.

    Article  PubMed  CAS  Google Scholar 

  • Sharp, P.A., 1985. On the origin of RNA splicing and introns. Cell 42: 397–400.

    Article  PubMed  CAS  Google Scholar 

  • Silvak, L.E., G. Pont-Kingdon, K. Le, G. Mayr, K.F. Tai, B.T. Stevens & W.L. Carroll, 1999. A novel intron element operates posttranscriptionally to regulate human N-myc expression. Mol. Cell. Biol. 19: 155–163.

    Google Scholar 

  • Simard, M.J. & B. Chabot, 2000. Control of hnRNP A1 alternative splicing: an intron element represses use of the common 3′ splice site. Mol. Cell. Biol. 20: 7353–7362.

    Article  PubMed  CAS  Google Scholar 

  • Takahara, T., S.I. Kanazu, S. Yanagisawa & H. Akanuma, 2000. Heterogeneous Spl mRNAs in human HepG2 cells include a product of homotypic trans-splicing. J. Biol. Chem. 275: 38067–38072.

    Article  PubMed  CAS  Google Scholar 

  • Weinsein, L.B. & J.A. Steitz, 1999. Guided tours: from precursor snoRNA to functional snoRNP. Curr. Opin. Cell Biol. 11: 378–384.

    Article  Google Scholar 

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Fedorova, L., Fedorov, A. (2003). Introns in gene evolution. In: Long, M. (eds) Origin and Evolution of New Gene Functions. Contemporary Issues in Genetics and Evolution, vol 10. Springer, Dordrecht. https://doi.org/10.1007/978-94-010-0229-5_3

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