Journal Article

Origin of alternative splicing by tandem exon duplication

Fyodor A. Kondrashov and Eugene V. Koonin

in Human Molecular Genetics

Volume 10, issue 23, pages 2661-2669
Published in print November 2001 | ISSN: 0964-6906
Published online November 2001 | e-ISSN: 1460-2083 | DOI:
Origin of alternative splicing by tandem exon duplication

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Genes with new functions often evolve by gene duplication. Alternative splicing is another means of evolutionary innovation in eukaryotes, which allows a single gene to encode functionally diverse proteins. We investigate a connection between these two evolutionary phenomena. For ∼10% of the described cases of substitution alternative splicing, such that either one or another amino acid sequence is included into the protein, evidence of origin by tandem exon duplication was found. This is a conservative estimate because alternative exons are typically short and, on many occasions, duplicates may have diverged beyond recognition. Dating exon duplications through a combination of the available experimental data on alternative splicing in orthologous genes from different species and computational analysis indicates that most of the duplications antedate at least the radiation of mammalian orders or even the radiation of vertebrate classes. At present, tandem exon duplication is the only mechanism of evolution of substitution alternative splicing that can be specifically demonstrated. Along with gene duplication, this could be a major route for generating functional diversity during evolution of multicellular eukaryotes.

Journal Article.  6040 words.  Illustrated.

Subjects: Genetics and Genomics

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