Evolutionary Conservation of Splice Sites

Abstract

The evolution of splice sites (both 5′ and 3′) is constrained. The results of the constraints are observed in conserved signatures exhibited by splice sites across species.

Keywords: splice sites; pre‐mRNA splicing; evolution; spliceosome; acceptor; donor

Figure 1.

A schematic showing the U2‐ and U12‐type splicing pathways. The dinucleotides at the end of the intron are highly conserved.

Figure 2.

Binding of U1 snRNA to 5′ss and features of 5′ss in human. Panel A shows the base pairing between the 5′ end of the U1 snRNA and the consensus 5′ss sequence. ψ denotes pseudo‐uridine, which is a modified uridine nucleotide. The figure shows the conventional numbering of positions, relative to the exon–intron boundary, e.g. −1G refers to nucleotide G at position −1. Panel B shows a pictorial representation of the position weight matrix (PWM) of the human U2‐type GT‐AG 5′ss; the bars represent the percentages of nucleotides at each position of the 5′ss. The table in the figure shows the percentages of nucleotides at each position. Adapted with permission from Roca et al. ().

Figure 3.

The consensus sequence of 5′ss in different species. The species are organized according to evolutionary relationship trees that are based on 18S ribosomal RNA conservation (not drawn to scale). Trichomonas vaginalis, Streblomastix strix and G. lamblia introns have not been demonstrated to be spliced by the U2‐ or U12‐type spliceosomes. Bacteria and archaea do not have spliceosomal introns.

Figure 4.

Information content in the exonic and intronic portions of GT‐AG U2 splice sites. Panel A shows the information content of the 5′ss GT‐AG U2 splice site in several species, whereas Panel B shows the information content of the 3′ss GT‐AG U2 splice site in the same species. Higher conservation is observed within exonic positions in 5′ss of higher organisms (Homo sapiens, Mus musculus, Arabidopsis thaliana), whereas lower organisms (C. elegans, D. melanogaster) show more conservation in the intronic portions of 5′ss. The 3′ss do not show much conservation except right at the exon–intron boundary. C. elegans in 3′ss shows some conservation in the intron due to pecularities of the U2AF binding to the PPT.

Figure 5.

Phylogenetic trees for splice site types from various species, using the information content of the sites. Panel A shows the tree for 5′ss from various species: A, A. thaliana; C, C. elegans; D, D. melanogaster; M, M. musculus and H, H. sapiens. Panel B shows the corresponding tree for 3′ss. The 5′ss predominantly cluster by type, whereas the 3′ss cluster predominantly by species, suggesting a more malleable architecture for the 3′ss and a more conserved structure for the 5′ss.

Figure 6.

Associations between pairs of positions within a 5′ss. Mouse is shown below the diagonal, whereas human is shown above the diagonal. Each square cell represents a pair of nucleotides, e.g. the cell addressed by row −3A and column −2G represents the pair −3A−2G in human 5′ss, whereas −2G−3A is a pair in the mouse 5′ss. The maroon colour represents depletion of the pair compared to the expected number, whereas the blue colour represents excess in the pair compared to the expected number. Brighter colours mean stronger depletion or excess over the expected numbers. The patterns seen here are conserved across species, suggesting an evolutionary pressure, probably arising from the spliceosome. Adapted with permission from Roca et al. ().

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References

Burge CB, Padgett RA and Sharp PA (1998) Evolutionary fates and origins of U12‐type introns. Molecular Cell 2: 773–785.

Hollins CD, MacMorris AMZ and Blumenthal T (2005) U2AF binding selects for the high conservation of the C. elegans 3′ splice site. RNA 11: 248–253.

Kent WJ and Zahler AM (2000) Conservation, regulation, synteny, and introns in a large‐scale C. briggsae–C. elegans genomic alignment. Genome Research 10: 1115–1125.

Nixon JE, Wang A, Morrison HG et al. (2002) A spliceosomal intron in Giardia lamblia. Proceedings of the National Academy of Sciences of the USA 99(6): 3701–3705.

Roca X, Olson AJ, Rao AR et al. (2008) Features of 5′‐splice‐site efficiency derived from disease‐causing mutations and comparative genomics. Genome Research 18(1): 77–87.

Sharp PA and Burge CB (1997) Classification of introns: U2‐type or U12‐type. Cell 91: 875–879.

Sheth N, Roca X, Hastings ML et al. (2006) Comprehensive splice‐site analysis using comparative genomics. Nucleic Acids Research 34: 3955–3967.

Further Reading

Gesteland RF, Cech TR and Atkins JF (eds) (2006) The RNA World, 3rd edn. University of Utah, Salt Lake City: Cold Spring Harbor Laboratory Press.

Irimia M, Penny D and Roy SW (2007) Coevolution of genomic intron number and splice sites. Trends in Genetics 23: 321–325.

Parmley JL, Urrutia AO, Potrzebowski L, Kaessmann H and Hurst LD (2007) Splicing and the evolution of proteins in mammals. PLoS Biology 5: e14.

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

Zhang C, Hastings ML, Krainer AR and Zhang MQ (2007) Dual‐specificity splice sites function alternatively as 5′ and 3′ splice sites. Proceedings of the National Academy of Sciences of the USA 104: 15028–15033.

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How to Cite close
Hastings, Michelle L., and Sachidanandam, Ravi(Apr 2008) Evolutionary Conservation of Splice Sites. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020782]