The DOI matches its Crossref record; 35 of the 36 references it cites were found in a registry or an index.
Near-neutrality in evolution of genes and gene regulation
Open accessAbstract
The nearly neutral theory contends that the interaction of drift and selection is important and occurs at various levels, including synonymous and nonsynonymous substitutions in protein coding regions and sequence turnover of regulatory elements. Recent progress of the theory is reviewed, and the interaction between drift and selection is suggested to differ at these different levels. Weak selective force on synonymous changes is stable, whereas its consequence on nonsynonymous changes depends on environmental factors. Selection on differentiation of regulatory elements is even more dependent on environmental factors than on amino acid changes. Of particular significance is the role of drift in the evolution of gene regulation that directly participates in morphological evolution. The range of near neutrality depends on the effective size of the population that is influenced by selected linked loci. In addition to the effective population size, molecular chaperones such as heat shock protein 90 have significant effects on the range of near neutrality.
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“Therefore, the fixation of nearly-neutral alleles of small selective effect is expected to be greatest in small populations 23,24 .”
From The modern molecular clock (2003) · cites this paper as [24]
In the citing paper
“The predicted correlation of generation time with mutation rate 24 has been supported by studies that compare the rates of molecular evolution with generation time (or its correlate, body size) across a range of genes for several vertebrate species 35,37-39 .”
From The modern molecular clock (2003) · cites this paper as [24]
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“Tomoko Ohta 22-24 provided an important extension of the neutral theory by recognizing the crucial role of effective population size in the influence of selection.”
From The modern molecular clock (2003) · cites this paper as [24]
In the citing paper
“So, a mutation would be effectively neutral if |s| < 1/4N e , where N e is the effective population size.”
From The modern molecular clock (2003) · cites this paper as [24]
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Citations
Cites
Mayr, E. (1963) · doi:10.4159/harvard.9780674865327 · Cited by 10,175
Adaptive protein evolution at the Adh locus in Drosophila
McDonald, J. H., & Kreitman, M. (1991) · Nature · doi:10.1038/351652a0 · Cited by 3,320
Hsp90 as a capacitor for morphological evolution
Rutherford, S. L., & Lindquist, S. (1998) · Nature · doi:10.1038/24550 · Cited by 2,270
The Probability of Duplicate Gene Preservation by Subfunctionalization
Lynch, M., & Force, A. G. (2000) · Genetics · doi:10.1093/genetics/154.1.459 · Cited by 1,559
Hsp90 as a capacitor of phenotypic variation
Queitsch, C., Sangster, T. A., & Lindquist, S. (2002) · Nature · doi:10.1038/nature749 · Cited by 1,372
The causes of molecular evolution
Gillespie, J. H. (1992) · Choice Reviews Online · doi:10.5860/choice.30-2064 · Cited by 1,214
The Nearly Neutral Theory of Molecular Evolution
Ohta, T. (1992) · Annual Review of Ecology and Systematics · doi:10.1146/annurev.es.23.110192.001403 · Cited by 1,149
Self-citationMechanisms of Speciation - A Population Genetic Approach
Templeton, A. R. (1981) · Annual Review of Ecology and Systematics · doi:10.1146/annurev.es.12.110181.000323 · Cited by 713
Akashi, H. D., & Gojobori, T. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.062526999 · Cited by 687
Adaptive protein evolution in Drosophila
Smith, N. G. C., & Eyre‐Walker, A. (2002) · Nature · doi:10.1038/4151022a · Cited by 677
Research works printed but not linked: 3
- Carroll S. B. Grenier J. K. & Weatherbee S. D. (2001) From DNA to Diversity (Blackwell Scientific Oxford).
- 10.1046/j.1420-9101.1999.00008.x · DOI
- Ohta T. (2002) Genetica in press.
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“Under this regime, mutations that moderately reduce molecular activity may have little or no effect on fitness, allowing nearly neutral or mildly deleterious variants to accumulate through genetic drift under relaxed purifying selection [73,74].”
Metadata
- Authors
- Ohta, T.
- Affiliations
- National Institute of Genetics (JP)
- Corresponding author
- Ohta, Tomoko
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2002-12-02
- Volume
- 99
- Issue
- 25
- Pages
- 16134-16137
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC138577
- OpenAlex
- W1963674435
- Cited by
- 333
- References
- 36
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 1 · 2023: 8 · 2022: 8 · 2021: 12 · 2020: 6 · 2019: 19 · 2018: 7 · 2017: 15 · 2016: 9 · 2015: 9 · 2014: 23 · 2013: 25 · 2012: 10
- FWCI
- 6.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Social Sciences › Arts and Humanities › History and Philosophy of Science › Philosophy of Biology and Scientific Explanation
- Keywords
- nearly neutral theory, genetic drift, natural selection, synonymous substitutions, nonsynonymous substitutions, gene regulatory evolution, morphological evolution, effective population size, linked loci, HSP90, molecular chaperones
- MeSH terms
- Animals, Drosophila, Drosophila melanogaster, Gene Expression Regulation, Genes, Genetic Linkage, Models, Genetic, Regulatory Sequences, Nucleic Acid, Selection, Genetic, Species Specificity, Arabidopsis, Molecular Chaperones, Evolution, Molecular, Amino Acid Substitution, Genetic Drift
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