ArticleRNA (New York, N.Y.)2008
Assessing the fraction of short-distance tandem splice sites under purifying selection.
Article in RNA (New York, N.Y.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Nucleotides in both donor and acceptor splice sites are responsible for choice in NAGNAG tandem splice sites.Cellular and molecular life sciences : CMLS · 2021Article
- Selection for reduced translation costs at the intronic 5' end in fungi.DNA research : an international journal for rapid publication of reports on genes and genomes · 2016Article
- Article
- Alternative splicing at GYNNGY 5' splice sites: more noise, less regulation.Nucleic acids research · 2014Article
- Physiological state co-regulates thousands of mammalian mRNA splicing events at tandem splice sites and alternative exons.Nucleic acids research · 2014Article
- A subtle alternative splicing event gives rise to a widely expressed human RNase k isoform.PloS one · 2014Article
- Alternative splicing of RNA triplets is often regulated and accelerates proteome evolution.PLoS biology · 2012Article
- Sequence features involved in the mechanism of 3' splice junction wobbling.BMC molecular biology · 2010Article
- TassDB2 - A comprehensive database of subtle alternative splicing events.BMC bioinformatics · 2010Article
- Identification and characterization of NAGNAG alternative splicing in the moss Physcomitrella patens.BMC plant biology · 2010Article
- Molecular determinants and evolutionary dynamics of wobble splicing.Molecular biology and evolution · 2009Article
- Alternative splicing at NAGNAG acceptors in Arabidopsis thaliana SR and SR-related protein-coding genes.BMC genomics · 2008Article
- Selection against tandem splice sites affecting structured protein regions.BMC evolutionary biology · 2008Article
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many alternative splice events result in subtle mRNA changes, and most of them occur at short-distance tandem donor and acceptor sites. The splicing mechanism of such tandem sites likely involves the stochastic selection of either splice site. While tandem splice events are frequent, it is unknown how many are functionally important. Here, we use phylogenetic conservation to address this question, focusing on tandems with a distance of 3-9 nucleotides. We show that previous contradicting results on whether alternative or constitutive tandem motifs are more conserved between species can be explained by a statistical paradox (Simpson's paradox). Applying methods that take biases into account, we found higher conservation of alternative tandems in mouse, dog, and even chicken, zebrafish, and Fugu genomes. We estimated a lower bound for the number of alternative sites that are under purifying (negative) selection. While the absolute number of conserved tandem motifs decreases with the evolutionary distance, the fraction under selection increases. Interestingly, a number of frameshifting tandems are under selection, suggesting a role in regulating mRNA and protein levels via nonsense-mediated decay (NMD). An analysis of the intronic flanks shows that purifying selection also acts on the intronic sequence. We propose that stochastic splice site selection can be an advantageous mechanism that allows constant splice variant ratios in situations where a deviation in this ratio is deleterious.
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