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Open Access Highly Accessed Research article

Conserved and species-specific alternative splicing in mammalian genomes

Ramil N Nurtdinov1, Alexey D Neverov2, Alexander V Favorov23, Andrey A Mironov124 and Mikhail S Gelfand14*

Author Affiliations

1 Faculty of Bioengineering and Bioinformatics, M.V. Lomonosov Moscow State University, Vorbyevy Gory 1-73, Moscow, 119992, Russia

2 State Research Institute for Genetics and Selection of Industrial Microorganisms "GosNIIGenetika", 1st Dorozhny proezd 1, Moscow, 117545, Russia

3 Division of Oncology Biostatistics and Bioinformatics, The Sidney Kimmel Cancer Center at Johns Hopkins, 550 North Broadway, Suite 1103, Baltimore, MD 21205, USA

4 Institute for Information Transmission Problems, Russian Academy of Sciences, Bolshoi Karenty pereulok 19, Moscow, 127994, Russia

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BMC Evolutionary Biology 2007, 7:249  doi:10.1186/1471-2148-7-249

Published: 22 December 2007

Abstract

Background

Alternative splicing has been shown to be one of the major evolutionary mechanisms for protein diversification and proteome expansion, since a considerable fraction of alternative splicing events appears to be species- or lineage-specific. However, most studies were restricted to the analysis of cassette exons in pairs of genomes and did not analyze functionality of the alternative variants.

Results

We analyzed conservation of human alternative splice sites and cassette exons in the mouse and dog genomes. Alternative exons, especially minor-isofom ones, were shown to be less conserved than constitutive exons. Frame-shifting alternatives in the protein-coding regions are less conserved than frame-preserving ones. Similarly, the conservation of alternative sites is highest for evenly used alternatives, and higher when the distance between the sites is divisible by three. The rate of alternative-exon and site loss in mouse is slightly higher than in dog, consistent with faster evolution of the former. The evolutionary dynamics of alternative sites was shown to be consistent with the model of random activation of cryptic sites.

Conclusion

Consistent with other studies, our results show that minor cassette exons are less conserved than major-alternative and constitutive exons. However, our study provides evidence that this is caused not only by exon birth, but also lineage-specific loss of alternative exons and sites, and it depends on exon functionality.