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Nucleic Acids Research Advance Access published online on October 5, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn677
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© 2008 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Genomics

Low conservation and species-specific evolution of alternative splicing in humans and mice: comparative genomics analysis using well-annotated full-length cDNAs

Jun-ichi Takeda1,2, Yutaka Suzuki2, Ryuichi Sakate1, Yoshiharu Sato1, Masahide Seki2, Takuma Irie2, Nono Takeuchi2, Takuya Ueda2, Mitsuteru Nakao3, Sumio Sugano2, Takashi Gojobori1,4 and Tadashi Imanishi1,*

1Integrated Database and Systems Biology Team, Biomedicinal Information Research Center, National Institute of Advanced Industrial Science and Technology, AIST Bio-IT Research Building, Aomi 2-42, Koto-ku, Tokyo 135-0064, 2Department of Medical Genome Sciences, Graduate School of Frontier Sciences, the University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, 3Laboratory for Plant Genome Informatics, Kazusa DNA Research Institute, 2-6-7 Kazusa-kamatari, Kisarazu, Chiba 292-0818 and 4Center for Information Biology and DDBJ, National Institute of Genetics, 1111 Yata, Mishima, Shizuoka 411-8540, Japan

*To whom correspondence should be addressed. Tel: +81 3 3599 8800; Fax: +81 3 3599 8801; Email: t.imanishi{at}aist.go.jp

Received July 8, 2008. Revised September 12, 2008. Accepted September 23, 2008.

Using full-length cDNA sequences, we compared alternative splicing (AS) in humans and mice. The alignment of the human and mouse genomes showed that 86% of 199 426 total exons in human AS variants were conserved in the mouse genome. Of the 20 392 total human AS variants, however, 59% consisted of all conserved exons. Comparing AS patterns between human and mouse transcripts revealed that only 431 transcripts from 189 loci were perfectly conserved AS variants. To exclude the possibility that the full-length human cDNAs used in the present study, especially those with retained introns, were cloning artefacts or prematurely spliced transcripts, we experimentally validated 34 such cases. Our results indicate that even retained-intron type transcripts are typically expressed in a highly controlled manner and interact with translating ribosomes. We found non-conserved AS exons to be predominantly outside the coding sequences (CDSs). This suggests that non-conserved exons in the CDSs of transcripts cause functional constraint. These findings should enhance our understanding of the relationship between AS and species specificity of human genes.


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