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The Emergence of Alternative 39 and 59 Splice Site Exons from Constitutive Exons

Summary: The Emergence of Alternative 39 and 59 Splice
Site Exons from Constitutive Exons
Eli Koren, Galit Lev-Maor, Gil Ast*
Department of Human Molecular Genetics, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Alternative 39 and 59 splice site (ss) events constitute a significant part of all alternative splicing events. These events
were also found to be related to several aberrant splicing diseases. However, only few of the characteristics that
distinguish these events from alternative cassette exons are known currently. In this study, we compared the
characteristics of constitutive exons, alternative cassette exons, and alternative 39ss and 59ss exons. The results
revealed that alternative 39ss and 59ss exons are an intermediate state between constitutive and alternative cassette
exons, where the constitutive side resembles constitutive exons, and the alternative side resembles alternative
cassette exons. The results also show that alternative 39ss and 59ss exons exhibit low levels of symmetry (frame-
preserving), similar to constitutive exons, whereas the sequence between the two alternative splice sites shows high
symmetry levels, similar to alternative cassette exons. In addition, flanking intronic conservation analysis revealed that
exons whose alternative splice sites are at least nine nucleotides apart show a high conservation level, indicating
intronic participation in the regulation of their splicing, whereas exons whose alternative splice sites are fewer than
nine nucleotides apart show a low conservation level. Further examination of these exons, spanning seven vertebrate
species, suggests an evolutionary model in which the alternative state is a derivative of an ancestral constitutive exon,
where a mutation inside the exon or along the flanking intron resulted in the creation of a new splice site that
competes with the original one, leading to alternative splice site selection. This model was validated experimentally on
four exons, showing that they indeed originated from constitutive exons that acquired a new competing splice site


Source: Ast, Gil - Department of Molecular Genetics and Biochemistry, Tel Aviv University


Collections: Biology and Medicine