Stochastic noise in splicing machinery
Open Access
- 22 June 2009
- journal article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 37 (14) , 4873-4886
- https://doi.org/10.1093/nar/gkp471
Abstract
The number of known alternative human isoforms has been increasing steadily with the amount of available transcription data. To date, over 100 000 isoforms have been detected in EST libraries, and at least 75% of human genes have at least one alternative isoform. In this paper, we propose that most alternative splicing events are the result of noise in the splicing process. We show that the number of isoforms and their abundance can be predicted by a simple stochastic noise model that takes into account two factors: the number of introns in a gene and the expression level of a gene. The results strongly support the hypothesis that most alternative splicing is a consequence of stochastic noise in the splicing machinery, and has no functional significance. The results are also consistent with error rates tuned to ensure that an adequate level of functional product is produced and to reduce the toxic effect of accumulation of misfolding proteins. Based on simulation of sampling of virtual cDNA libraries, we estimate that error rates range from 1 to 10% depending on the number of introns and the expression level of a gene.Keywords
This publication has 53 references indexed in Scilit:
- Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencingNature Genetics, 2008
- Large-scale identification and characterization of alternative splicing variants of human gene transcripts using 56 419 completely sequenced and manually annotated full-length cDNAsNucleic Acids Research, 2006
- The importance of being divisible by three in alternative splicingNucleic Acids Research, 2005
- How prevalent is functional alternative splicing in the human genome?Trends in Genetics, 2004
- Low conservation of alternative splicing patterns in the human and mouse genomesHuman Molecular Genetics, 2003
- Conservation of human alternative splice events in mouseNucleic Acids Research, 2003
- Alternative splicing in the human, mouse and rat genomes is associated with an increased frequency of exon creation and/or lossNature Genetics, 2003
- Increase of functional diversity by alternative splicingTrends in Genetics, 2003
- A genomic view of alternative splicingNature Genetics, 2002
- Frequent Alternative Splicing of Human GenesGenome Research, 1999