Alternative Splicing: Evolution

Abstract

Alternative splicing of pre‐messenger ribonucleic acid (pre‐mRNA) allows the generation of different mRNAs from the same gene. Evolution of alternative splicing affecting translated regions of mRNAs permits the synthesis of different proteins from a single gene, significantly increasing the diversity of the protein repertoire.

Keywords: spliceosome; splice site; donor site; acceptor site; branch site

Figure 1.

Duplication of an exon (B) via intronic recombination also duplicates adjacent regions of the flanking introns, including the 5′ donor site of the downstream intron (hatched lines) and the 3′ acceptor site of the upstream intron (thick black lines). Because the duplicated splice sites (which are present in the chimeric and the original introns) are likely to compete in splicing, the duplicated exons may be either skipped or included in the transcripts.

Figure 2.

Exon insertion by intronic recombination also inserts adjacent regions of the flanking introns, including the 5′ donor site of the downstream intron (thick black lines) and the 3′ acceptor site of the upstream intron (hatched lines). Because the original 5′ and 3′ splice‐site combination may be more favourable than the two novel splice‐site combinations, initially the inserted exon may be skipped in most mRNAs.

close

References

Akiva P, Toporik A, Edelheit S et al. (2006) Transcription‐mediated gene fusion in the human genome. Genome Research 16: 30–36.

Blencowe BJ (2006) Alternative splicing: new insights from global analyses. Cell 126: 37–47.

Caceres JF, Stamm S, Helfman DM and Krainer AR (1994) Regulation of alternative splicing in vivo by overexpression of antagonistic splicing factors. Science 265: 1706–1709.

Chen FC, Chaw SM, Tzeng YH, Wang SS and Chuang TJ (2007) Opposite evolutionary effects between different alternative splicing patterns. Molecular Biology and Evolution 24: 1443–1446.

Dowbenko DJ, Diep A, Taylor BA, Lusis AJ and Lasky LA (1991) Characterization of the murine homing receptor gene reveals correspondence between protein domains and coding exons. Genomics 9: 270–277.

Dytrych L, Sherman DL, Gillespie CS and Brophy PJ (1998) Two PDZ domain proteins encoded by the murine periaxin gene are the result of alternative intron retention and are differentially targeted in Schwann cells. Journal of Biological Chemistry 273: 5794–5800.

Gutman A and Kornblihtt AR (1987) Identification of a third region of cell‐specific alternative splicing in human fibronectin mRNA. Proceedings of the National Academy of Sciences of the USA 84: 7179–7182.

Humphries RK, Ley T, Goldsmith ME et al. (1983) ‘Silent’ nucleotide substitution in codon 24 of a β+‐thalassemia globin gene activates splice site in coding sequence RNA. Progress in Clinical Biology Research 134: 123–126.

Kim H, Klein R, Majewski J and Ott J (2004) Estimating rates of alternative splicing in mammals and invertebrates. Nature Genetics 36: 915–916.

Kim E, Magen A and Ast G (2007) Different levels of alternative splicing among eukaryotes. Nucleic Acids Research 35: 125–131.

Kornblihtt AR, Pesce CG, Alonso CR et al. (1996) The fibronectin gene as a model for splicing and transcription studies. FASEB Journal 10: 248–257.

MacLeod JN, Burton‐Wurster N, Gu DN and Lust G (1996) Fibronectin mRNA splice variant in articular cartilage lacks bases encoding the V, III‐15, and I‐10 protein segments. Journal of Biological Chemistry 271: 18954–18960.

Magrangeas F, Pitiot G, Dubois S et al. (1998) Cotranscription and intergenic splicing of human galactose‐1‐phosphate uridylyltransferase and interleukin‐11 receptor alpha‐chain genes generate a fusion mRNA in normal cells. Implication for the production of multidomain proteins during evolution. Journal of Biological Chemistry 273: 16005–16010.

Parra G, Reymond A, Dabbouseh N et al. (2006) Tandem chimerism as a means to increase protein complexity in the human genome. Genome Research 16: 37–44.

Patthy L (1987) Intron‐dependent evolution: preferred types of exons and introns. FEBS Letters 214: 1–7.

Patthy L (1991) Modular exchange principles in proteins. Current Opinion in Structural Biology 1: 351–361.

Patthy L (1999) Genome evolution and the evolution of exon‐shuffling: a review. Gene 238: 103–114.

Plass M and Eyras E (2006) Differentiated evolutionary rates in alternative exons and the implications for splicing regulation. BMC Evolutionary Biology 6: 50.

Stamm S, Ben‐Ari S and Rafalska I (2005) Function of alternative splicing. Gene 344: 1–20.

Talavera D, Vogel C, Orozco M, Teichmann SA and de la Cruz X (2007) The (in)dependence of alternative splicing and gene duplication. PLoS Computational Biology 3: e33.

Tress ML, Martelli PL, Frankish A et al. (2007) The implications of alternative splicing in the ENCODE protein complement. Proceedings of the National Academy of Sciences of the USA 104: 5495–5500.

Wagener R, Kobbe B and Paulsson M (1998) Genomic organisation, alternative splicing and primary structure of human matrilin‐4. FEBS Letters 438: 165–170.

Yeo GW, Nostrand EL and Liang TY (2007) Discovery and analysis of evolutionarily conserved intronic splicing regulatory elements. PLoS Genetics 3: e85.

Yoshimura K, Chu CS and Crystal RG (1993) Alternative splicing of intron 23 of the human cystic fibrosis transmembrane conductance regulator gene resulting in a novel exon and transcript coding for a shortened intracytoplasmic C terminus. Journal of Biological Chemistry 268: 686–690.

Zhang MQ (1998) Statistical features of human exons and their flanking regions. Human Molecular Genetics 7: 919–932.

Zhang C, Krainer AR and Zhang MQ (2007) Evolutionary impact of limited splicing fidelity in mammalian genes. Trends in Genetics 23: 484–488.

Zhuo D, Madden R, Elela SA and Chabot B (2007) Modern origin of numerous alternatively spliced human introns from tandem arrays. Proceedings of the National Academy of Sciences of the USA 104: 882–886.

Further Reading

Bhasi A, Pandey RV, Utharasamy SP and Senapathy P (2007) EuSplice: a unified resource for the analysis of splice signals and alternative splicing in eukaryotic genes. Bioinformatics 23: 1815–1823.

Kim N, Alekseyenko AV, Roy M and Lee C (2007) The ASAP II database: analysis and comparative genomics of alternative splicing in 15 animal species. Nucleic Acids Research 35(Database issue): D93–D98.

Smith CW and Valcarcel J (2000) Alternative pre‐mRNA splicing: the logic of combinatorial control. Trends in Biochemical Sciences 25: 381–388.

Zavolan M and van Nimwegen E (2006) The types and prevalence of alternative splice forms. Current Opinion in Structural Biology 16: 362–367.

Useful Internet Resources

ESEfinder is a web resource that identifies exonic splicing enhancers. http://rulai.cshl.edu/tools/ESE/index.html.

EuSplice is a unique resource which provides reliable splice signal and alternative splicing information for 23 eukaryotic genomes. http://66.170.16.154/EuSplice/.

The ACESCAN2 Web Server is an online tool for identifying candidate cis‐elements (exonic splicing enhancers and silencers, intronic splicing enhancers) in alternative and constitutive splicing in mammalian exons. http://genes.mit.edu/acescan2/index.html.

The Alternative Exon Database (AEDB) is a manually generated database for human alternative exons and their properties: the data is gathered from literature where these exons have been experimentally verified. http://www.ebi.ac.uk/asd/aedb/index.html.

The Alternative Splicing Database (ASD) Project aims to understand the mechanism of alternative splicing on a genome‐wide scale by creating a database of alternative splice events and the resultant isoform splice patterns of genes from human, and other model species. http://www.ebi.ac.uk/asd/.

The AltExtron Database is a computer generated high quality dataset of human transcript‐confirmed constitutive and alternative exons and introns. http://www.ebi.ac.uk/asd/altextron/index.html.

The FAS‐ESS Web Server is an online tool for the systematic identification and analysis of exonic splicing silencers. http://genes.mit.edu/fas‐ess/.

The RESCUE‐ESE Web Server is an online tool for identifying candidate ESEs in vertebrate exons. http://genes.mit.edu/burgelab/rescue‐ese/.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Patthy, László(Apr 2008) Alternative Splicing: Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005084.pub2]