Evidence map›Paper›PMID 40011430›Full record

ArticleNature communications2025

Interpreting mammalian synonymous site conservation in light of the unwanted transcript hypothesis.

Matthew J Christmas, Michael X Dong, Jennifer R S Meadows, Sergey V Kozyrev, Kerstin Lindblad-Toh

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Matthew J ChristmasDepartment of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden. matthew.christmas@imbim.uu.se.ORCID http://orcid.org/0000-0002-6355-7581
Michael X DongDepartment of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
Jennifer R S MeadowsDepartment of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.ORCID http://orcid.org/0000-0002-0850-230X
Sergey V KozyrevDepartment of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.ORCID http://orcid.org/0000-0001-6209-4100
Kerstin Lindblad-TohDepartment of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.ORCID http://orcid.org/0000-0001-8338-0253

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mammalian genomes are biased towards GC bases at third codon positions, likely due to a GC-biased ancestral genome and the selectively neutral recombination-related process of GC-biased gene conversion. The unwanted transcript hypothesis posits that this high GC content at synonymous sites may be beneficial for protecting against spurious transcripts, particularly in species with low effective population sizes. Utilising a 240 placental mammal genome alignment and single-base resolution conservation scores, we interpret sequence conservation at mammalian four-fold degenerate sites in this context and find evidence in support of the unwanted transcript hypothesis, including a strong GC bias, high conservation at sites relating to exon splicing, less human genetic variation at conserved four-fold degenerate sites, and conservation of sites important for epigenetic regulation of developmental genes. Additionally, we show that high conservation of four-fold degenerate sites in essential developmental genes, including homeobox genes, likely relates to the low mutation rates experienced by these genes.

Indexed as

Conserved SequenceMammalsAnimalsBase CompositionCodonEvolution, MolecularExonsGenomeHumansCodon

Identifiers

PMID40011430
PMCPMC11865589

What OpenQuestion holds

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Registered trials

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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.