A likelihood approach for comparing synonymous and nonsynonymous nucleotide substitution rates, with application to the chloroplast genome.
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A model of DNA sequence evolution applicable to coding regions is presented. This represents the first evolutionary model that accounts for dependencies among nucleotides within a codon. The model uses the codon, as opposed to the nucleotide, as the unit of evolution, and is parameterized in terms of synonymous and nonsynonymous nucleotide substitution rates. One of the model's advantages over those used in methods for estimating synonymous and nonsynonymous substitution rates is that it completely corrects for multiple hits at a codon, rather than taking a parsimony approach and considering only pathways of minimum change between homologous codons. Likelihood-ratio versions of the relative-rate test are constructed and applied to data from the complete chloroplast DNA sequences of Oryza sativa, Nicotiana tabacum, and Marchantia polymorpha. Results of these tests confirm previous findings that substitution rates in the chloroplast genome are subject to both lineage-specific and locus-specific effects. Additionally, the new tests suggest tha the rate heterogeneity is due primarily to differences in nonsynonymous substitution rates. Simulations help confirm previous suggestions that silent sites are saturated, leaving no evidence of heterogeneity in synonymous substitution rates.
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The first codon models estimated parameters representing an averaged nonsynonymous-synonymous rate ratio.
“The first codon models estimated parameters representing an averaged nonsynonymous-synonymous rate ratio.”
From RELAX: Detecting Relaxed Selection in a Phylogenetic Framework (2015) · cites this paper as Muse and Gaut 1994
The Probabilistic Model for Codon Evolution section says the model’s parameters determine synonymous and nonsynonymous substitution rates. But Parameter Interpretation describes the estimated parameters as products of instantaneous rates and time, not as an averaged nonsynonymous-to-synonymous rate ratio; its averaging over codons concerns expected substitution counts. (LLM, conf=0.82)
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- Authors
- Muse, S. V., & Gaut, B. S.
- Affiliations
- North Carolina State University (US)
- Venue
- Molecular Biology and Evolution
- Publisher
- Oxford University Press (OUP)
- Published
- 1994-09
- Volume
- 11
- Issue
- 5
- Pages
- 715-24
- ISSN
- 0737-4038 (ISSN-L)
- 1537-1719
- OpenAlex
- W1881807356
- Cited by
- 920
- References
- 2
- Citations by year
- 2026: 25 · 2025: 19 · 2024: 22 · 2023: 16 · 2022: 25 · 2021: 27 · 2020: 30 · 2019: 50 · 2018: 28 · 2017: 27 · 2016: 45 · 2015: 25 · 2014: 51 · 2013: 44 · 2012: 39
- FWCI
- 3.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Biology and Evolution (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (16250)
- National Institutes of Health (16250)
- National Institute of General Medical Sciences (F32GM016250, GM-16250, F32GM015528, R01GM032518, GM15528, GM32518)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- synonymous substitution rate, nonsynonymous substitution rate, relative rate tests, likelihood ratio test, chloroplast genome, rate heterogeneity, rice, tobacco, Marchantia polymorpha
- MeSH terms
- Chloroplasts, Codon, Computer Simulation, Models, Genetic, Phylogeny, Plants, Plants, Toxic, Oryza, Sequence Homology, Nucleic Acid, Nicotiana, Likelihood Functions, Point Mutation, DNA, Chloroplast
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