ArticleCell systems2018
Alternative Polyadenylation of Mammalian Transcripts Is Generally Deleterious, Not Adaptive.
Article in Cell systems, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- Coding regions are rarely predefined in the eukaryotic genomes: a note on simplified models of gene architecture.BMC genomics · 2026Article
- Functionality versus Adaptation: Insights from Transcriptional Adaptation.Journal of molecular evolution · 2026Review
- APAdeg enhances differentially expressed gene inference by leveraging site-specific signals in APA-seq data.Briefings in bioinformatics · 2026Article
- Article
- Transcript diversity reflects deleterious RNA processing errors shaped by population size in metazoans.PLoS biology · 2026Article
- The implications of alternative splicing regulation for maximum lifespan.Nature communications · 2025Article
- The Implications of Alternative Splicing Regulation for Maximum Lifespan.bioRxiv : the preprint server for biology · 2025Article
- Morphogenesis, starvation, and light responses in a mushroom-forming fungus revealed by long-read sequencing and extensive expression profiling.Cell genomics · 2025Article
- Most m5C Modifications in Mammalian mRNAs are Nonadaptive.Molecular biology and evolution · 2025Article
- Review
- Landscape of alternative splicing and polyadenylation during growth and development of muscles in pigs.Communications biology · 2024Article
- Genetic and selective constraints on the optimization of gene product diversity.bioRxiv : the preprint server for biology · 2024Article
- GTDrift: a resource for exploring the interplay between genetic drift, genomic and transcriptomic characteristics in eukaryotes.NAR genomics and bioinformatics · 2024Article
- Article
- Multiplexed screening reveals how cancer-specific alternative polyadenylation shapes tumor growth in vivo.Nature communications · 2024Article
- Quantifying negative selection in human 3' UTRs uncovers constrained targets of RNA-binding proteins.Nature communications · 2024Article
- Genes for highly abundant proteins in Escherichia coli avoid 5' codons that promote ribosomal initiation.PLoS computational biology · 2023Article
- Gene product diversity: adaptive or not?Trends in genetics : TIG · 2022Review
- Alternative splicing as a source of phenotypic diversity.Nature reviews. Genetics · 2022Review
- Article
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2 authors.
Funding
Abstract
Alternative polyadenylation (APA) produces from the same gene multiple mature RNAs with varying 3' ends. Although APA is commonly believed to generate beneficial functional diversity and be adaptive, we hypothesize that most genes have one optimal polyadenylation site and that APA is caused largely by deleterious polyadenylation errors. The error hypothesis, but not the adaptive hypothesis, predicts that, as the expression level of a gene increases, its polyadenylation diversity declines, relative use of the major (presumably optimal) polyadenylation site increases, and that of each minor (presumably nonoptimal) site decreases. It further predicts that the number of polyadenylation signals per gene is smaller than the random expectation and that polyadenylation signals for major but not minor sites are under purifying selection. All of these predictions are confirmed in mammals, suggesting that numerous defective RNAs are produced in normal cells, many phenotypic variations at the molecular level are nonadaptive, and cellular life is noisier than is appreciated.
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