Stochastic noise in splicing machinery.

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TitleStochastic noise in splicing machinery.
Publication TypeJournal Article
Year of Publication2009
AuthorsMelamud, E, Moult, J
JournalNucleic Acids Res
Volume37
Issue14
Pagination4873-86
Date Published2009 Aug
ISSN1362-4962
KeywordsAlternative Splicing, Expressed Sequence Tags, Gene Library, Humans, Introns, Models, Genetic, Protein Isoforms, Stochastic Processes, Transcription, Genetic
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.

DOI10.1093/nar/gkp471
Alternate JournalNucleic Acids Res.
PubMed ID19546110
PubMed Central IDPMC2724286
Grant ListP01 GM57890 / GM / NIGMS NIH HHS / United States