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  • Review Article
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The evolution of spliceosomal introns: patterns, puzzles and progress

Key Points

  • Recent studies have uncovered the extent and pattern of conservation of intron position across widely diverged eukaryotic species.

  • Introns that are found in the genomes of modern species are mainly fairly old, with significant fractions dating to relatively deep eukaryotic ancestors.

  • Conservation of spliceosomal components across diverse eukaryotic lineages suggests the presence of a complex spliceosome in the ancestor of all extant eukaryotes.

  • This pattern of conservation might indicate that introns were already numerous in early eukaryotes, with diverse eukaryotic lineages having subsequently experienced more intron loss than gain, although debate is ongoing.

  • Analysis of apparent cases of intron loss indicates that such loss might occur through recombination between the genomic copy of the gene and a reverse transcript of a spliced mRNA copy of the gene.

  • Analysis of introns that seem to have been gained over the past 10–100 million years indicates that the new introns could arise as transposon insertions into contiguous coding sequence, not by transposition of previous introns, which was the previously favoured model.

  • Previous proposals for the causes of the vast differences between numbers of introns between eukaryotic species, which were based on inter-specific differences in either the selective value of introns or population size, have trouble explaining the apparently large numbers of introns in fairly deep eukaryotic ancestors. We propose that many of these intron-number differences could be explained by intron-loss rates.

Abstract

The origins and importance of spliceosomal introns comprise one of the longest-abiding mysteries of molecular evolution. Considerable debate remains over several aspects of the evolution of spliceosomal introns, including the timing of intron origin and proliferation, the mechanisms by which introns are lost and gained, and the forces that have shaped intron evolution. Recent important progress has been made in each of these areas. Patterns of intron-position correspondence between widely diverged eukaryotic species have provided insights into the origins of the vast differences in intron number between eukaryotic species, and studies of specific cases of intron loss and gain have led to progress in understanding the underlying molecular mechanisms and the forces that control intron evolution.

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Figure 1: Distribution of spliceosomal introns in eukaryotic species.
Figure 2: Intron conservation, gain and loss for 684 sets of eukaryotic orthologues.
Figure 3: Models and examples of intron loss.
Figure 4: Models and examples of intron gain.
Figure 5: Strange patterns of intron loss and gain.

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References

  1. Cannone, J. J. et al. The comparative RNA web (CRW) site: an online database of comparative sequence and structure information for ribosomal, intron, and other RNAs. MBC Bioinformatics 3, 2 (2002).

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  3. Lambowitz, A. M. & Zimmerly, S. Mobile group II introns. Annu. Rev. Genet. 38, 1–35 (2004).

    Article  CAS  PubMed  Google Scholar 

  4. Jurica, M. S. & Moore, M. J. Pre-mRNA splicing: awash in a sea of proteins. Mol. Cell 12, 5–14 (2003).

    Article  CAS  PubMed  Google Scholar 

  5. Cech, T. R. The generality of self-splicing RNA: relationship to nuclear mRNA splicing. Cell 44, 207–210. (1986).

    Article  CAS  PubMed  Google Scholar 

  6. Rogers, J. H. How were introns inserted into nuclear genes? Trends Genet. 5, 213–216 (1989). Two of the five current models of intron creation are proposed in this speculative piece.

    Article  CAS  PubMed  Google Scholar 

  7. Sharp, P. A. Five easy pieces. Science 254, 663 (1991).

    Article  CAS  PubMed  Google Scholar 

  8. Cavalier-Smith, T. Intron phylogeny: a new hypothesis. Trends Genet. 7, 145–148 (1991). An important statement of the idea that introns might be descended from type II introns that are transferred from early eukaryotic organelles.

    Article  CAS  PubMed  Google Scholar 

  9. Stoltzfus, A. On the possibility of constructive neutral evolution. J. Mol. Evol. 49, 169–181 (1999).

    Article  CAS  PubMed  Google Scholar 

  10. Llopart, A., Comeron, J. M., Brunet, F. G., Lachaise, D. & Long, M. Intron presence–absence polymorphism in Drosophila driven by positive Darwinian selection. Proc. Natl Acad. Sci. USA 99, 8121–8126 (2002). The sole known cases of polymorphic intron absence–presence within a species, notably in a gene with a fascinating evolutionary history.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Iwamoto, M., Maekawa, M., Saito, A., Higo, H. & Higo, K. Evolutionary relationship of plant catalase genes inferred from intron–exon structures: isozyme divergence after the separation of monocots and dicots. Theor. Appl. Genet. 97, 9–19 (1998). The first convincing case of intron gain in which the source of the intron, an inserted SINE element, is clear.

    Article  CAS  Google Scholar 

  12. Iwamoto, M., Nagashima, H., Nagamine, T., Higo, H. & Higo, K. p-SINE1-like intron of the CatA catalase homologs and phylogenetic relationships among AA-genome Oryza and related species. Theor. Appl. Genet. 98, 853–861 (1999).

    Article  CAS  Google Scholar 

  13. Hankeln, T., Friedl, H., Ebersberger, I., Martin, J. & Schmidt, E. R. A variable intron distribution in globin genes of Chironomus: evidence for recent intron gain. Gene 205, 151–160 (1997).

    Article  CAS  PubMed  Google Scholar 

  14. Dawkins, R. The Selfish Gene (Oxford Univ. Press, 1976).

    Google Scholar 

  15. Orgel, L. E. & Crick, F. H. Selfish DNA: the ultimate parasite. Nature 284, 604–607 (1980).

    Article  CAS  PubMed  Google Scholar 

  16. Doolittle, W. F. & Sapienza, C. Selfish genes, the phenotype paradigm and genome evolution. Nature 284, 601–603 (1981). Along with reference 15, this article contains early statements of the idea of genome evolution by insertion of selfish elements and differential selection on such elements between species of different complexity.

    Article  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  18. Britten, R. J. & Davidson, E. H. Gene regulation for higher cells: a theory. Science 165, 349–357 (1969).

    Article  CAS  PubMed  Google Scholar 

  19. Britten, R. J. & Davidson, E. H. Repetitive and non-repetitive DNA sequences and a speculation on the origins of evolutionary novelty. Q. Rev. Biol. 46, 111–138 (1971).

    Article  CAS  PubMed  Google Scholar 

  20. Lynch, M. Intron evolution as a population-genetic process. Proc. Natl Acad. Sci. USA 99, 6118–6123 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lynch, M. & Conery, J. The origins of genome complexity. Science 302, 1401–1404 (2002).

    Article  CAS  Google Scholar 

  22. Gilbert, W. Why genes in pieces? Nature 271, 501 (1978).

    Article  CAS  PubMed  Google Scholar 

  23. Doolittle, W. F. Genes in pieces – were they ever together? Nature 272, 581–582 (1978).

    Article  Google Scholar 

  24. Blake, C. C. F. Do genes in pieces imply proteins in pieces? Nature 273, 267 (1978). References 22–24 provide the backbone of the IE theory.

    Article  Google Scholar 

  25. Perler, F. et al. The evolution of genes — the chicken preproinsulin gene. Cell 20, 555–566 (1980).

    Article  CAS  PubMed  Google Scholar 

  26. Go, M. Correlation of DNA exonic regions with protein structural units in haemoglobin. Nature 291, 90–92 (1981).

    Article  CAS  PubMed  Google Scholar 

  27. Stone, E. M., Rothblum, K. N. & Schwartz, R. J. Intron-dependent evolution of chicken glyceraldehyde phosphate dehydrogenase gene. Nature 313, 498–500 (1985).

    Article  CAS  PubMed  Google Scholar 

  28. Straus, D. & Gilbert, W. Genetic engineering in the Precambrian: structure of the chicken triosephosphate isomerase gene. Mol. Cell Biol. 5, 3497–3506 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. De Souza, S. J., Long, M., Schoenbach, L., Roy, S. W. & Gilbert., W. Introns correlate with module boundaries in ancient proteins. Proc. Natl Acad. Sci. USA 93, 14632–14636 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. De Souza, S. J. et al. Towards a resolution of the introns early/late debate: only phase zero introns are correlated with the structure of ancient proteins. Proc. Natl Acad. Sci. USA 95, 5094–5099 (1998). An important early statement of the 'synthetic' or 'mixed' variant of the IE theory.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Roy, S. W., Nosaka, M., de Souza, S. J. & Gilbert, W. Centripetal modules and ancient introns. Gene 238, 85–91 (1999).

    Article  CAS  PubMed  Google Scholar 

  33. Fedorov, A. et al. Intron distribution difference for 276 ancient and 131 modern genes suggests the existence of ancient introns. Proc. Natl Acad. Sci. USA 98, 13177–13182 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Roy, S. W., Lewis, B. P., Fedorov, A. & Gilbert, W. Footprints of primordial introns on the eukaryotic genome. Trends Genet. 17, 496–498 (2001).

    Article  CAS  PubMed  Google Scholar 

  35. Fedorov, A., Roy, S., Cao, X. & Gilbert, W. Phylogenetically older introns strongly correlate with module boundaries in ancient proteins. Genome Res. 13, 1155–1157 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Roy, S. W., Fedorov, A. & Gilbert, W. The signal of ancient introns is obscured by intron density and homolog number. Proc. Natl Acad. Sci. USA 99, 15513–15517 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. De Souza, S. J. The emergence of a synthetic theory of intron evolution. Genetica 118, 117–121 (2003).

    Article  CAS  PubMed  Google Scholar 

  38. Roy, S. W. Recent evidence for the exon theory of genes. Genetica 118, 251–266 (2003).

    Article  CAS  PubMed  Google Scholar 

  39. Patthy, L. Genome evolution and the evolution of exon-shuffling — a review. Gene 238, 103–114 (1999). A comprehensive review of the known cases of exon shuffling.

    Article  CAS  PubMed  Google Scholar 

  40. Patthy, L. Modular assembly of genes and the evolution of new functions. Genetica 118, 217–231 (2003).

    Article  CAS  PubMed  Google Scholar 

  41. Tonegawa, S., Maxam, A. M., Tizard, R., Bernard, O. & Gilbert, W. Sequence of a mouse germ-line gene for a variable region of an immunoglobulin light chain. Proc. Natl Acad. Sci. USA 75, 1485–1489 (1978).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Comeron, J. M. & Kreitman, M. The correlation between intron length and recombination in Drosophila. Dynamic equilibrium between mutational and selective forces. Genetics 156, 1175–1190 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Duret, L. Why do genes have introns? Recombination might add a new piece to the puzzle. Trends Genet. 17, 172–175 (2001).

    Article  CAS  PubMed  Google Scholar 

  44. Lynch, M. & Kewalramani, A. Messenger RNA surveillance and the evolutionary proliferation of introns. Mol. Biol. Evol. 20, 563–571 (2003).

    Article  CAS  PubMed  Google Scholar 

  45. Cavalier-Smith, T. Selfish DNA and the origin of introns. Nature 315, 283–284 (1985). An important early statement of the IL hypothesis.

    Article  CAS  PubMed  Google Scholar 

  46. Sharp, P. A. On the origin of RNA splicing and introns. Cell 42, 397–400 (1985).

    Article  CAS  PubMed  Google Scholar 

  47. Dibb, N. J. & Newman, A. J. Evidence that introns arose at proto-splice sites. EMBO J. 8, 2015–2021 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Palmer, J. D. & Logsdon, J. M. Jr. The recent origin of introns. Curr. Opin. Genet. Dev. 1, 470–477 (1991).

    Article  CAS  PubMed  Google Scholar 

  49. Stoltzfus, A., Spencer, D. F., Zuker, M., Logsdon, J. M. Jr & Doolittle, W. F. Testing the exon theory of genes: the evidence from protein structure. Science 265, 202–207 (1994).

    Article  CAS  PubMed  Google Scholar 

  50. Stoltzfus, A. Origin of introns — early or late? Nature 369, 526–527 (1994).

    Article  CAS  PubMed  Google Scholar 

  51. Logsdon, J. M. Jr et al. Seven newly discovered intron positions in the triose-phosphate isomerase gene: evidence for the introns-late theory. Proc. Natl Acad. Sci. USA 92, 8507–8511 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Kwaitowski, J., Krawczyk, M., Kornacki, M., Bailey, K. & Ayala, F. J. Evidence against the exon theory of genes derived from the triose-phosphate isomerase gene. Proc. Natl Acad. Sci. USA 92, 8503–8506 (1995).

    Article  Google Scholar 

  53. Cho, G. & Doolittle, R. F. Intron distribution in ancient paralogs supports random insertion and not random loss. J. Mol. Evol. 44, 573–584 (1997).

    Article  CAS  PubMed  Google Scholar 

  54. Rzhetsky, A., Ayala, F. J., Hsu, L. C., Chang, C. & Yoshida, A. Exon/intron structure of aldehyde dehydrogenase genes supports the 'introns-late' theory. Proc. Natl Acad. Sci. USA 94, 6820–6825 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Logsdon, J. M. Jr. The recent origins of spliceosomal introns revisited. Curr. Opin. Genet. Dev. 8, 637–648 (1998).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  57. Fedoro v, A. F., Merican, A. F. & Gilbert, W. Large-scale comparison of intron positions among animal, plant, and fungal genes. Proc. Natl Acad. Sci. USA 99, 16128–16133 (2002).

    Article  CAS  Google Scholar 

  58. Rogozin, I. B., Wolf, Y. I., Sorokin, A. V., Mirkin, B. G. & Koonin, E. V. Remarkable interkingdom conservation of intron positions and massive, lineage-specific intron loss and gain in eukaryotic evolution. Curr. Biol. 13, 1512–1517 (2003).

    Article  CAS  PubMed  Google Scholar 

  59. Tarrio, R., Rodriguez-Trelles, F. & Ayala, F. J. A new Drosophila spliceosomal intron position is common in plants. Proc. Natl Acad. Sci. USA 100, 6580–6583 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Dibb, N. J. Proto-splice site model of intron origin. J. Theor. Biol. 151, 405–416 (1991).

    Article  CAS  PubMed  Google Scholar 

  61. Paquette, S. M., Bak, S & Feyereisen, R. Intron–exon organization and phylogeny in a large superfamily, the paralogous cytochrome P450 genes of Arabidopsis thaliana. DNA Cell Biol. 19, 307–317 (2000).

    Article  CAS  PubMed  Google Scholar 

  62. Sverdlov, A. V., Rogozin, I. B., Babenko, V. N. & Koonin, E. V. Reconstruction of ancestral protosplice sites. Curr. Biol. 14, 1505–1508 (2004).

    Article  CAS  PubMed  Google Scholar 

  63. Coghlan, A. & Wolfe, K. H. Origins of recently gained introns in Caenorhabditis. Proc. Natl Acad. Sci. USA 101, 11362–11367 (2004). The first sequence analysis of a large number of putative recently gained introns. The results are interpreted by the authors as evidence for intron transposition, although the answer might not be so straightforward.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Qiu, W. G., Schisler, N. & Stoltzfus, A. The evolutionary gain of spliceosomal introns: sequence and phase preferences. Mol. Biol. Evol. 21, 1252–1263 (2004).

    Article  CAS  PubMed  Google Scholar 

  65. Tordai, H. & Patthy, L. Insertion of spliceosomal introns in proto-splice sites: the case of secretory signal peptides. FEBS Lett. 575, 109–111 (2004).

    Article  CAS  PubMed  Google Scholar 

  66. Sadusky, T., Newman, A. J. & Dibb, N. J. Exon junction sequences as cryptic splice sites: implications for intron origin. Curr. Biol. 14, 505–509 (2004).

    CAS  PubMed  Google Scholar 

  67. Stoltzfus, A. Molecular evolution: introns fall into place. Curr. Biol. 14, R351–352 (2004).

    Article  CAS  PubMed  Google Scholar 

  68. Sverdlov, A. V., Rogozin, I. B., Babenko, V. N. & Koonin, E. V. Conservation versus parallel gains in intron evolution. Nucleic Acids Res. 33, 1741–1748 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Roy, S. W. & Gilbert, W. Complex early genes. Proc. Natl Acad. Sci. USA 102, 1986–1991 (2005). The reanalysis of data from reference 58, which indicates that intron loss, not gain, has dominated intron evolution.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Rogozin, I. B., Sverdlov, A. V., Babenko, V. N. & Koovin, E. V. Analysis of evolution of exon–intron structure in eukaryotic genes. Brief Bioinform. 6, 118–134.

  71. Roy, S. W., Fedorov, A. & Gilbert, W. Large-scale comparison of intron positions in mammalian genes shows intron loss but no gain. Proc. Natl Acad. Sci. USA 100, 7158–7162 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Cho, S., Jin, S. W., Cohen, A. & Ellis, R. E. A phylogeny of Caenorhabditis reveals frequent loss of introns during nematode evolution. Genome Res. 14, 1207–1220 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Kiontke, K. et al. Caenorhabditis phylogeny predicts convergence of hermaphroditism and extensive intron loss. Proc. Natl Acad. Sci. USA 101, 9003–9008 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Robertson, H. M. Two large families of chemoreceptor genes in the nematodes Caenorhabditis elegans and Caenorhabditis briggsae reveal extensive gene duplication, diversification, movement, and intron loss. Genome Res. 8, 449–463 (1998).

    Article  CAS  PubMed  Google Scholar 

  75. Wolf, Y. I., Kondrashov, F. A. & Koonin, E. V. Footprints of primordial introns on the eukaryotic genome: still no clear traces. Trends Genet. 17, 499–501 (2001).

    Article  CAS  PubMed  Google Scholar 

  76. Seo, H. C. et al. Miniature genome in the marine chordate Oikopleura dioica. Science 294, 2506 (2001).

    Article  CAS  PubMed  Google Scholar 

  77. Edvardsen, R. B. et al. Hypervariable and highly divergent intron–exon organizations in the chordate Oikopleura dioica. J. Mol. Evol. 59, 448–457 (2004).

    Article  CAS  PubMed  Google Scholar 

  78. Babenko, V. N., Rogozin, I. B., Mekhedov, S. L. & Koonin, E. V. Prevalence of intron gain over intron loss in the evolution of paralogous gene families. Nucleic Acids Res. 32, 3724–3733 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Embley, T. M. & Hirt, R. P. Early branching eukaryotes? Curr. Opin. Genet. Dev. 8, 624–629 (1998).

    Article  CAS  PubMed  Google Scholar 

  80. Simpson, A. G. & Roger, A. J. Eukaryotic evolution: getting to the root of the problem. Curr. Biol. 12, R691–R693 (2002).

    Article  CAS  PubMed  Google Scholar 

  81. Sogin, M. L. Early evolution and the origin of eukaryotes. Curr. Opin. Genet. Dev. 1, 457–463 (1991).

    Article  CAS  PubMed  Google Scholar 

  82. Hashimoto, T. & Hasegawa, M. Origin and early evolution of eukaryotes inferred from the amino acid sequences of translation elongation factors 1α/Tu and 2/G. Adv. Biophys. 32, 73–120 (1996).

    Article  CAS  PubMed  Google Scholar 

  83. Stiller, J. W., Duffield, E. C. & Hall, B. D. Amitochondriate amoebae and the evolution of DNA-dependent RNA polymerase II. Proc. Natl Acad. Sci. USA 95, 11769–11774 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Biderre, C., Metenier, G. & Vivares, C. P. A small spliceosomal-type intron occurs in a ribosomal protein gene of the microsporidian Encephalitozoon cuniculi. Mol. Biochem. Parasitol. 94, 283–286 (1998).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Fast, N. M. & Doolittle, W. F. Trichomonas vaginalis possesses a gene encoding the essential spliceosomal component, PRP8. Mol. Biochem. Parasitol. 99, 275–278 (1999).

    Article  CAS  PubMed  Google Scholar 

  87. Breckenridge, D. G, Watanabe, Y., Greenwood, S. J., Gray, M. W. & Schnare, M. N. U1 small nuclear RNA and spliceosomal introns in Euglena gracilis. Proc. Natl Acad. Sci. USA 96, 852–856 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Ismaili, N. et al. Characterization of a SR protein from Trypanosoma brucei with homology to RNA-binding cis-splicing proteins. Mol. Biochem. Parasitol. 102, 103–105 (1999).

    Article  CAS  PubMed  Google Scholar 

  89. Schnare, M. N. & Gray, M. W. Structural conservation and variation among U5 small nuclear RNAs from trypanosomatid protozoa. Biochim. Biophys. Acta. 1490, 362–366 (2000).

    Article  CAS  PubMed  Google Scholar 

  90. Dacks, J. B. & Doolittle, W. F. Reconstructing/deconstructing the earliest eukaryotes: how comparative genomics can help. Cell 107, 419–425 (2001).

    Article  CAS  PubMed  Google Scholar 

  91. Edgcomb, V. P., Roger, A. J., Simpson, A. G., Kysela, D. T. & Sogin, M. L. Evolutionary relationships among 'jakobid' flagellates as indicated by α- and β-tubulin phylogenies. Mol. Biol. Evol. 18, 514–522 (2001).

    Article  CAS  PubMed  Google Scholar 

  92. Archibald, J. M., O'Kelly, C. J. & Doolittle, W. F. The chaperonin genes of jakobid and jakobid-like flagellates: implications for eukaryotic evolution. Mol. Biol. Evol. 19, 422–431 (2002).

    Article  CAS  PubMed  Google Scholar 

  93. Nixon, J. E. et al. A spliceosomal intron in Giardia lamblia. Proc. Natl Acad. Sci. USA 99, 3701–3705 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Simpson, A. G., MacQuarrie, E. K & Roger, A. J. Eukaryotic evolution: early origin of canonical introns. Nature 419, 270 (2002).

    Article  CAS  PubMed  Google Scholar 

  95. Collins, L. & Penny, D. Complex spliceosomal organization ancestral to extant eukaryotes. Mol. Biol. Evol. 22, 1053–1066 (2005). A demonstration of the presence of a sophisticated spliceosome in the common ancestor of all extant eukaryotes.

    Article  CAS  PubMed  Google Scholar 

  96. Vanacova, S., Yan, W., Carlton, J. M. & Johnson, P. J. Spliceosomal introns in the deep-branching eukaryote Trichomonas vaginalis. Proc. Natl Acad. Sci. USA 102, 4430–4435 (2005).

    Article  CAS  PubMed  Google Scholar 

  97. Anantharaman, V., Koonin, E. V. & Aravind, L. Comparative genomics and evolution of proteins involved in RNA metabolism. Nucleic Acids. Res. 30, 1427–1464 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Ruvinsky, A., Eskesen, S. T., Eskesen, F. N. & Hurst, L. D. Can codon usage bias explain intron phase distributions and exon symmetry? J. Mol. Evol. 60, 99–104 (2005).

    Article  CAS  PubMed  Google Scholar 

  99. Long, M., de Souza, S. J., Rosenberg, C. & Gilbert, W. Relationship between 'proto-splice sites' and intron phases: evidence from dicodon analysis. Proc. Natl Acad. Sci. USA 95, 219–223 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  101. Bernstein, L. B., Mount, S. M. & Weiner, A. M. Pseudogenes for human small nuclear RNA U3 appear to arise by integration of self-primed reverse transcripts of the RNA into new chromosomal sites. Cell 32, 461–472 (1983).

    Article  CAS  PubMed  Google Scholar 

  102. Lewin, R. How mammalian RNA returns to its genome. Science 219, 1052–1054 (1983).

    Article  CAS  PubMed  Google Scholar 

  103. Weiner, A. M., Deininger, P. L. & Efstratiadis, A. Nonviral retroposons: genes, pseudogenes, and transposable elements generated by the reverse flow of genetic information. Annu. Rev. Biochem. 55, 631–661 (1986).

    Article  CAS  PubMed  Google Scholar 

  104. Fink, G. R. Pseudogenes in yeast? Cell 49, 5–6 (1987).

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  106. Derr, L. K. The involvement of cellular recombination and repair genes in RNA-mediated recombination in Saccharomyces cerevisiae. Genetics 148, 937–945 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Kent, W. J. & Zahler, A. M. Conservation, regulation, synteny, and introns in a large-scale C. briggsae–C. elegans genomic alignment. Genome Res. 10, 1115–1125 (2000).

    Article  CAS  PubMed  Google Scholar 

  108. Fedorova, L. & Fedorov, A. Introns in gene evolution. Genetica 118, 123–131 (2003).

    Article  CAS  PubMed  Google Scholar 

  109. Nielsen, C. B., Friedman, B., Birren, B., Burge, C. B. & Galagan, J. E. Patterns of intron gain and loss in fungi. PLoS Biol. 2, e422 (2004).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  110. Banyai, L. & Patthy, L. Evidence that human genes of modular proteins have retained significantly more ancestral introns than their fly or worm orthologues. FEBS Lett. 565, 127–132 (2004).

    Article  CAS  PubMed  Google Scholar 

  111. Sakurai, A. et al. On biased distribution of introns in various eukaryotes. Gene 300, 89–95 (2002).

    Article  CAS  PubMed  Google Scholar 

  112. Mourier, T. & Jeffares, D. C. Eukaryotic intron loss. Science 300, 1393 (2003).

    Article  CAS  PubMed  Google Scholar 

  113. Frugoli, J. A., McPeek, M. A., Thomas, T. L. & McClung, C. R. Intron loss and gain during evolution of the catalase gene family in angiosperms. Genetics 149, 355–365 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Wada, H. et al. Dynamic insertion-deletion of introns in deuterostome EF-1a genes. J. Mol. Evol. 54, 118–128 (2002).

    Article  CAS  PubMed  Google Scholar 

  115. Sverdlov, A. V., Babenko, V. N., Rogozin, I. B. & Koonin, E. V. Preferential loss and gain of introns in 3′ portions of genes suggests a reverse-transcription mechanism of intron loss. Gene 338, 85–91 (2004).

    Article  CAS  PubMed  Google Scholar 

  116. Roy, S. W. & Gilbert, W. The pattern of intron loss. Proc. Natl Acad. Sci. USA 102, 713–718 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Crick, F. H. Chromosome structure and function — future prospects. Eur. J. Biochem. 83, 1–3 (1978).

    Article  CAS  PubMed  Google Scholar 

  118. Crick, F. Split genes and RNA splicing. Science 204, 264–271 (1979).

    Article  CAS  PubMed  Google Scholar 

  119. Tsujimoto, Y. & Suzuki, Y. The DNA sequence of Bombyx-mori fibroin gene including the 5′ flanking, mRNA coding, entire intervening and fibroin protein coding regions. Cell 18, 591–600 (1979).

    Article  CAS  PubMed  Google Scholar 

  120. Giroux, M. J. et al. De novo synthesis of an intron by the maize transposable element Dissociation. Proc. Natl Acad. Sci. USA 91, 12150–12154 (1994). The authors show that a transposable element inserted into the Sh2 gene of maize is sometimes exactly spliced out of transcripts, supporting the idea that transposable element insertions could give rise to new introns in some cases.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Rogers, J. H. The role of introns in evolution. FEBS Lett. 268, 339–343 (1990).

    Article  CAS  PubMed  Google Scholar 

  122. Roy, S. W. The origin of recent introns: transposons? Genome Biol. 5, 251 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  123. Roy, S. W. & Gilbert, W. Rates of intron loss and gain: implications for early eukaryotic evolution. Proc. Natl Acad. Sci. USA 102, 5773–5778 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Guiliano, D. B. et al. Conservation of long-range synteny and microsynteny between the genomes of two distantly related nematodes. Genome Biol. 3, research 0057 (2002).

    Article  Google Scholar 

  125. Gao, L. Z. & Innan, H. Very low gene duplication rate in the yeast genome. Science 306, 1367–1370 (2004).

    Article  CAS  PubMed  Google Scholar 

  126. Krzywinski, J. & Besansky, N. J. Frequent intron loss in the white gene: a cautionary tale for phylogeneticists. Mol. Biol. Evol. 19, 362–366 (2002).

    Article  CAS  PubMed  Google Scholar 

  127. Hentze, M. W. & Kulozik, A. E. A perfect message: RNA surveillance and nonsense-mediated decay. Cell 96, 307–310 (1999).

    Article  CAS  PubMed  Google Scholar 

  128. Ast, G. How did alternative splicing evolve? Nature Rev. Genet. 5, 773–782 (2004).

    Article  CAS  PubMed  Google Scholar 

  129. Castillo-Davis, C. I., Mekhedov, S. L., Hartl, D. L., Koonin, E. V. & Kondrashov, F. A. Selection for short introns in highly expressed genes. Nature Genet. 31, 415–418 (2002).

    Article  CAS  PubMed  Google Scholar 

  130. Ometto, L., Stephan, W. & De Lorenzo, D. Insertion/deletion and nucleotide polymorphism data reveal constraints in Drosophila melanogaster introns and intergenic regions. Genetics 169, 1521–1527 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Prachumwat, A., DeVincentis, L. & Palopoli, M. F. Intron size correlates positively with recombination rate in Caenorhabditis elegans. Genetics 166, 1585–1590 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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FURTHER INFORMATION

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Saccharomyces Genome Database

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Glossary

Nonsense-mediated decay

A mechanism by which a stop codon that is encountered by the ribosome upstream of an intron–exon boundary leads to degradation of the transcript.

Exon shuffling

A process by which ectopic recombination within introns leads to the creation of new genetic products.

Dollo parsimony

A method in which a character (in this case an intron position) is inferred to have arisen exactly once on the evolutionary tree in the ancestor of the most distantly related pair of species that share the character. Absence of the character in descendents of this ancestor is then explained by the minimal pattern of losses necessary to explain the observed phylogenetic distribution.

Maximum likelihood analysis

A statistical method that finds the maximum of the likelihood function given a set of data, where the likelihood function gives the probability of obtaining the data for a set of unknown variables.

Protosplice sites

A consensus motif into which newly inserted introns seem to insert (or at least in which they are found), which is generally thought to be a variant of MAG|GT, where M denotes an A or C, and the line indicates the point of insertion.

Gene conversion

Any process by which a genomic element changes to the sequence of a paralogous element; this probably takes place mainly by double recombination.

Fixation

With respect to a given mutant, the condition in which all alleles in the population are descendents of that mutant.

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William Roy, S., Gilbert, W. The evolution of spliceosomal introns: patterns, puzzles and progress. Nat Rev Genet 7, 211–221 (2006). https://doi.org/10.1038/nrg1807

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