ArticleGenome research2003
Neutral substitutions occur at a faster rate in exons than in noncoding DNA in primate genomes.
Article in Genome research, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 124 citations in OpenAlex.
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- Population-level genome-wide STR discovery and validation for population structure and genetic diversity assessment of Plasmodium species.PLoS genetics · 2022Article
- Lack of CpG islands in human unitary pseudogenes and its implication.Mammalian genome : official journal of the International Mammalian Genome Society · 2021Article
- Investigation of Interferon Gamma Activity Using Bioinformatics Methods.Archives of Razi Institute · 2021Article
- The Long-Term Evolutionary History of Gradual Reduction of CpG Dinucleotides in the SARS-CoV-2 Lineage.Biology · 2021Article
- Mutational bias and the protein code shape the evolution of splicing enhancers.Nature communications · 2020Article
- An analysis of mutational signatures of synonymous mutations across 15 cancer types.BMC medical genetics · 2019Article
- Mode and Tempo of Microsatellite Length Change in a Malaria Parasite Mutation Accumulation Experiment.Genome biology and evolution · 2019Article
- Variable BaselineFrontiers in immunology · 2019Article
- Insights IntoFrontiers in genetics · 2018Article
- Molecular discrimination of tall fescue morphotypes in association with Festuca relatives.PloS one · 2018Article
- Depletion of somatic mutations in splicing-associated sequences in cancer genomes.Genome biology · 2017Article
- Regulatory remodeling in the allo-tetraploid frog Xenopus laevis.Genome biology · 2017Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Point mutation rates in exons (synonymous sites) and noncoding (introns and intergenic) regions are generally assumed to be the same. However, comparative sequence analyses of synonymous substitutions in exons (81 genes) and that of long intergenic fragments (141.3 kbp) of human and chimpanzee genomes reveal a 30%-60% higher mutation rate in exons than in noncoding DNA. We propose a differential CpG content hypothesis to explain this fundamental, and seemingly unintuitive, pattern. We find that the increased exonic rate is the result of the relative overabundance of synonymous sites involved in CpG dinucleotides, as the evolutionary divergence in non-CpG sites is similar in noncoding DNA and synonymous sites of exons. Expectations and predictions of our hypothesis are confirmed in comparisons involving more distantly related species, including human-orangutan, human-baboon, and human-macaque. Our results suggest an underlying mechanism for higher mutation rate in GC-rich genomic regions, predict nonlinear accumulation of mutations in pseudogenes over time, and provide a possible explanation for the observed higher diversity of single nucleotide polymorphisms (SNPs) in the synonymous sites of exons compared to the noncoding regions.
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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.