Global analysis of alternative splicing differences between humans and chimpanzees
| Autor: | Qun Pan, Benjamin J. Blencowe, Todd M. Preuss, John A. Calarco, Joseph P. Calarco, Christopher Lee, Mario Cáceres, Xinshu Xiao, Yi Xing |
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| Rok vydání: | 2007 |
| Předmět: |
Pan troglodytes
Biology Transfection Gene Expression Regulation Enzymologic Evolution Molecular Exon Species Specificity Genetics Animals Humans RNA Messenger Gene Glutathione Transferase Oligonucleotide Array Sequence Analysis Expressed Sequence Tags Comparative genomics Genome Human Gene Expression Profiling Alternative splicing Intron Genetic Variation Exons Genomics Introns Isoenzymes Gene expression profiling Alternative Splicing RNA splicing Human genome Research Paper HeLa Cells Plasmids Developmental Biology |
| Zdroj: | Genes & Development. 21:2963-2975 |
| ISSN: | 1549-5477 0890-9369 |
| DOI: | 10.1101/gad.1606907 |
| Popis: | Alternative splicing is a powerful mechanism affording extensive proteomic and regulatory diversity from a limited repertoire of genes. However, the extent to which alternative splicing has contributed to the evolution of primate species-specific characteristics has not been assessed previously. Using comparative genomics and quantitative microarray profiling, we performed the first global analysis of alternative splicing differences between humans and chimpanzees. Surprisingly, 6%–8% of profiled orthologous exons display pronounced splicing level differences in the corresponding tissues from the two species. Little overlap is observed between the genes associated with alternative splicing differences and the genes that display steady-state transcript level differences, indicating that these layers of regulation have evolved rapidly to affect distinct subsets of genes in humans and chimpanzees. The alternative splicing differences we detected are predicted to affect diverse functions including gene expression, signal transduction, cell death, immune defense, and susceptibility to diseases. Differences in expression at the protein level of the major splice variant of GlutathioneS-transferase omega-2 (GSTO2), which functions in the protection against oxidative stress and is associated with human aging-related diseases, suggests that this enzyme is less active in human cells compared with chimpanzee cells. The results of this study thus support an important role for alternative splicing in establishing differences between humans and chimpanzees. |
| Databáze: | OpenAIRE |
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