ArticleGenome research2014
Error-prone polymerase activity causes multinucleotide mutations in humans.
Article in Genome research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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.
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.
Who cites it
59 citing papers in PubMed, 112 citations in OpenAlex.
- Genome-wide annotation of human multi-nucleotide variants reveals widespread functional differences from single nucleotide variants.Nature communications · 2026Article
- Epistasis among clustered lineage-specific amino acid substitutions in the Drosophila Trio protein.PLoS genetics · 2026Article
- Inferring hominin history with recurrent gene flow from single unphased genomes and a two-locus statistic.bioRxiv : the preprint server for biology · 2026Article
- Long-read sequencing of families reveals increased germline and postzygotic mutation rates in repetitive DNA.Nature communications · 2026Article
- Accurate prediction of substitution rates at protein sites with a mutation-selection model.Scientific reports · 2025Article
- Efficient discovery of frequently co-occurring mutations in a sequence database with matrix factorization.PLoS computational biology · 2025Article
- Germline mutation rates and fine-scale recombination parameters in zebra finch.PLoS genetics · 2025Article
- Mutation and recombination parameters in zebra finch are similar to those in mammals.bioRxiv : the preprint server for biology · 2025Article
- How antisense transcripts can evolve to encode novel proteins.Nature communications · 2024Article
- The divergence of mutation rates and spectra across the Tree of Life.EMBO reports · 2023Review
- Evolutionary Shortcuts via Multinucleotide Substitutions and Their Impact on Natural Selection Analyses.Molecular biology and evolution · 2023Article
- CDMAP/CDVIS: context-dependent mutation analysis package and visualization software.G3 (Bethesda, Md.) · 2023Article
- Neutral Models of De Novo Gene Emergence Suggest that Gene Evolution has a Preferred Trajectory.Molecular biology and evolution · 2023Article
- Chromatin structure influences rate and spectrum of spontaneous mutations inGenome research · 2023Article
- Atomistic simulation of protein evolution reveals sequence covariation and time-dependent fluctuations of site-specific substitution rates.PLoS computational biology · 2023Article
- Using landscape genomics to assess local adaptation and genomic vulnerability of a perennial herbFrontiers in genetics · 2023Article
- Pharmacogenomic profile of actionable molecular variants related to drugs commonly used in anesthesia: WES analysis reveals new mutations.Frontiers in pharmacology · 2023Article
- Next-generation development and application of codon model in evolution.Frontiers in genetics · 2023Review
- Variant calling: Considerations, practices, and developments.Human mutation · 2022Review
- Enabling Inference for Context-Dependent Models of Mutation by Bounding the Propagation of Dependency.Journal of computational biology : a journal of computational molecular cell biology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
About 2% of human genetic polymorphisms have been hypothesized to arise via multinucleotide mutations (MNMs), complex events that generate SNPs at multiple sites in a single generation. MNMs have the potential to accelerate the pace at which single genes evolve and to confound studies of demography and selection that assume all SNPs arise independently. In this paper, we examine clustered mutations that are segregating in a set of 1092 human genomes, demonstrating that the signature of MNM becomes enriched as large numbers of individuals are sampled. We estimate the percentage of linked SNP pairs that were generated by simultaneous mutation as a function of the distance between affected sites and show that MNMs exhibit a high percentage of transversions relative to transitions, findings that are reproducible in data from multiple sequencing platforms and cannot be attributed to sequencing error. Among tandem mutations that occur simultaneously at adjacent sites, we find an especially skewed distribution of ancestral and derived alleles, with GC → AA, GA → TT, and their reverse complements making up 27% of the total. These mutations have been previously shown to dominate the spectrum of the error-prone polymerase Pol ζ, suggesting that low-fidelity DNA replication by Pol ζ is at least partly responsible for the MNMs that are segregating in the human population. We develop statistical estimates of MNM prevalence that can be used to correct phylogenetic and population genetic inferences for the presence of complex mutations.
Indexed as
Identifiers
What OpenQuestion holds
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.