Low conservation and species-specific evolution of alternative splicing in humans and mice: comparative genomics analysis using well-annotated full-length cDNAs.
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.
Integrated 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, Japan.
Jun-Ichi
J
Takeda
Yutaka
Y
Suzuki
Ryuichi
R
Sakate
Yoshiharu
Y
Sato
Masahide
M
Seki
Takuma
T
Irie
Nono
N
Takeuchi
Takuya
T
Ueda
Mitsuteru
M
Nakao
Sumio
S
Sugano
Takashi
T
Gojobori
Tadashi
T
Imanishi
D017398:Alternative Splicing; D000604:Amino Acyl-tRNA Synthetases / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D018076:DNA, Complementary / Q000737:chemistry*; D003627:Data Interpretation, Statistical; D019143:Evolution, Molecular; D005091:Exons; D023281:Genomics; D006801:Humans; D007438:Introns; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000737:chemistry; D013045:Species Specificity
D018076:DNA, Complementary; D012333:RNA, Messenger; D019869:Phosphatidylinositol 3-Kinases; D000604:Amino Acyl-tRNA Synthetases; C019975:cysteinyl-tRNA synthetase