ReviewNature reviews. Genetics2024
Selection on synonymous sites: the unwanted transcript hypothesis.
Review in Nature reviews. Genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Bioengineering strategies for improving the immunogenicity of mRNA vaccines.Signal transduction and targeted therapy · 2026Review
- The therapeutic potential of transposable element activity modulation.EMBO molecular medicine · 2026Review
- Enhancing protein expression in humans through codon optimization with transformer and contrastive learning.Molecular therapy. Nucleic acids · 2026Article
- Rapid GC content evolution in rice through GC-biased gene conversion and selection for translation efficiency.Nature communications · 2026Article
- Probing the limits of genetic recoding using multi-omics-guided evolution.Nature communications · 2026Article
- Prime editor-based high-throughput screening reveals functional synonymous mutations in human cells.Nature biotechnology · 2026Article
- Why do we have so many different transcripts?PLoS biology · 2026Article
- Nuclear effects play an important role in determining codon usage-dependent human gene expression.Nature communications · 2025Article
- Bacterial gene 5' ends have unusual mutation rates that can mislead tests of selection.PLoS biology · 2025Article
- Codon Usage Bias in Human RNA Viruses and Its Impact on Viral Translation, Fitness, and Evolution.Viruses · 2025Review
- Co-option of an endogenous retrovirus (LTR7-HERVH) in early human embryogenesis: becoming useful and going unnoticed.Mobile DNA · 2025Review
- Why AGG is associated with high transgene output: passenger effects and their implications for transgene design.NAR genomics and bioinformatics · 2025Article
- RID is required for both repeat-induced point mutation and nucleation of a novel transitional heterochromatic state for euchromatic repeats.Nucleic acids research · 2025Article
- Interpreting mammalian synonymous site conservation in light of the unwanted transcript hypothesis.Nature communications · 2025Article
- Translation of the downstream ORF from bicistronic mRNAs by human cells: Impact of codon usage and splicing in the upstream ORF.Protein science : a publication of the Protein Society · 2025Article
- Codon Bias of theInternational journal of molecular sciences · 2024Article
- Comparative Analysis of Codon Usage Bias in SixInternational journal of molecular sciences · 2024Article
- Synthetic genomes unveil the effects of synonymous recoding.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
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Authors and funding
4 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although translational selection to favour codons that match the most abundant tRNAs is not readily observed in humans, there is nonetheless selection in humans on synonymous mutations. We hypothesize that much of this synonymous site selection can be explained in terms of protection against unwanted RNAs - spurious transcripts, mis-spliced forms or RNAs derived from transposable elements or viruses. We propose not only that selection on synonymous sites functions to reduce the rate of creation of unwanted transcripts (for example, through selection on exonic splice enhancers and cryptic splice sites) but also that high-GC content (but low-CpG content), together with intron presence and position, is both particular to functional native mRNAs and used to recognize transcripts as native. In support of this hypothesis, transcription, nuclear export, liquid phase condensation and RNA degradation have all recently been shown to promote GC-rich transcripts and suppress AU/CpG-rich ones. With such 'traps' being set against AU/CpG-rich transcripts, the codon usage of native genes has, in turn, evolved to avoid such suppression. That parallel filters against AU/CpG-rich transcripts also affect the endosomal import of RNAs further supports the unwanted transcript hypothesis of synonymous site selection and explains the similar design rules that have enabled the successful use of transgenes and RNA vaccines.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.