ArticleGenome biology2017
The fitness cost of mis-splicing is the main determinant of alternative splicing patterns.
Article in Genome biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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67 citing papers in PubMed, 108 citations in OpenAlex.
- Pervasive noise in human pre-mRNA splice site selection.Molecular cell · 2026Article
- Splicing deficiency is driven by genomic erosion in non-recombining algal mating-type chromosomes.PLoS biology · 2026Article
- The tiny germline chromosomes of Paramecium aurelia have an exceptionally high recombination rate and are capped by a new class of Helitrons.BMC biology · 2026Article
- Wanted: A population genetic theory of biological noise regulation.PLoS genetics · 2026Article
- Transcript diversity reflects deleterious RNA processing errors shaped by population size in metazoans.PLoS biology · 2026Article
- Splicing regulation and intron evolution in the short-intron ciliate model of endosymbiosis Paramecium bursaria.Nucleic acids research · 2026Article
- De Novo Genome Sequence Assembly of the RNAi-Tractable Paramecium bursaria 186b: An Endosymbiotic Model System.Genome biology and evolution · 2025Article
- Cataloging the potential functional diversity of Cacna1e splice variants using long-read sequencing.BMC genomics · 2025Article
- A PGRPLC1/Rel2-F axis controls Anopheles gambiae resistance to systemic infections with Gram-positive bacteria containing Lys-type peptidoglycan.PLoS pathogens · 2025Article
- Impact of Acute Endurance Exercise on Alternative Splicing in Skeletal Muscle.FASEB bioAdvances · 2025Article
- Impact of Acute Endurance Exercise on Alternative Splicing in Skeletal Muscle.bioRxiv : the preprint server for biology · 2025Article
- Splicing accuracy varies across human introns, tissues, age and disease.Nature communications · 2025Article
- Most m5C Modifications in Mammalian mRNAs are Nonadaptive.Molecular biology and evolution · 2025Article
- Full-length RNA transcript sequencing traces brain isoform diversity in house mouse natural populations.Genome research · 2024Article
- Re-appraising the evidence for the source, regulation and function of p53-family isoforms.Nucleic acids research · 2024Review
- Profiling genetically driven alternative splicing across the Indonesian archipelago.American journal of human genetics · 2024Article
- Global impact of unproductive splicing on human gene expression.Nature genetics · 2024Article
- Genetic and selective constraints on the optimization of gene product diversity.bioRxiv : the preprint server for biology · 2024Article
- Characterization of alternative splicing during mammalian brain development reveals the extent of isoform diversity and potential effects on protein structural changes.Biology open · 2024Article
- GTDrift: a resource for exploring the interplay between genetic drift, genomic and transcriptomic characteristics in eukaryotes.NAR genomics and bioinformatics · 2024Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMost eukaryotic genes are subject to alternative splicing (AS), which may contribute to the production of protein variants or to the regulation of gene expression via nonsense-mediated messenger RNA (mRNA) decay (NMD). However, a fraction of splice variants might correspond to spurious transcripts and the question of the relative proportion of splicing errors to functional splice variants remains highly debated.
resultsWe propose a test to quantify the fraction of AS events corresponding to errors. This test is based on the fact that the fitness cost of splicing errors increases with the number of introns in a gene and with expression level. We analyzed the transcriptome of the intron-rich eukaryote Paramecium tetraurelia. We show that in both normal and in NMD-deficient cells, AS rates strongly decrease with increasing expression level and with increasing number of introns. This relationship is observed for AS events that are detectable by NMD as well as for those that are not, which invalidates the hypothesis of a link with the regulation of gene expression. Our results show that in genes with a median expression level, 92-98% of observed splice variants correspond to errors. We observed the same patterns in human transcriptomes and we further show that AS rates correlate with the fitness cost of splicing errors.
conclusionsThese observations indicate that genes under weaker selective pressure accumulate more maladaptive substitutions and are more prone to splicing errors. Thus, to a large extent, patterns of gene expression variants simply reflect the balance between selection, mutation, and drift.
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