Origin of alternative splicing by tandem exon duplication

• Published in: Human molecular genetics Vol. 10; no. 23; pp. 2661 - 2669
• Main Authors: KONDRASHOV, Fyodor A, KOONIN, Eugene V
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.11.2001
• Subjects: Alternative Splicing - genetics; Amino Acid Sequence; Animals; Biological and medical sciences; Databases, Protein; Evolution, Molecular; Exons - genetics; Fundamental and applied biological sciences. Psychology; Gene Duplication; Genetic Variation; Humans; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Sequence Alignment; Sequence Homology, Amino Acid; Tandem Repeat Sequences - genetics; Transcription. Transcription factor. Splicing. Rna processing; Alternative splicing; Gene duplication; Exon; Tandemly repeated sequence; Computerized processing
• ISSN: 0964-6906; 1460-2083; 1460-2083
• DOI: 10.1093/hmg/10.23.2661

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 approximately 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.