Likelihood models for detecting positively selected amino acid sites and applications to the HIV-1 envelope gene
Abstract
Several codon-based models for the evolution of protein-coding DNA sequences are developed that account for varying selection intensity among amino acid sites. The “neutral model” assumes two categories of sites at which amino acid replacements are either neutral or deleterious. The “positive-selection model” assumes an additional category of positively selected sites at which nonsynonymous substitutions occur at a higher rate than synonymous ones. This model is also used to identify target sites for positive selection. The models are applied to a data set of the V3 region of the HIV-1 envelope gene, sequenced at different years after the infection of one patient. The results provide strong support for variable selection intensity among amino acid sites The neutral model is rejected in favor of the positive-selection model, indicating the operation of positive selection in the region. Positively selected sites are found in both the V3 region and the flanking regions.
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The introduction of site-to-site rate variation allowed detection of individual sites evolving under positive selection by classifying sites into different rate categories and estimating a separate ! value specifically for the sites in the positive selection category.
“The introduction of site-to-site rate variation allowed detection of individual sites evolving under positive selection, by classifying sites into different rate categories and estimating a separate !value specifically for the sites in the positive selection category (Nielsen and Yang 1998).”
From RELAX: Detecting Relaxed Selection in a Phylogenetic Framework (2015) · cites this paper as Nielsen and Yang 1998
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- Authors
- Nielsen, R., & Yang, Z.
- Affiliations
- University of California, Berkeley (US)
- University College London (GB)
- Corresponding author
- Nielsen, Rasmus
- Venue
- Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 1998-03-01
- Volume
- 148
- Issue
- 3
- Pages
- 929-936
- ISSN
- 0016-6731 (ISSN-L)
- 1943-2631
- OpenAlex
- W2133585817
- Cited by
- 1,622
- References
- 2
- Citations by year
- 2026: 15 · 2025: 19 · 2024: 44 · 2023: 38 · 2022: 33 · 2021: 36 · 2020: 41 · 2019: 60 · 2018: 48 · 2017: 46 · 2016: 53 · 2015: 67 · 2014: 91 · 2013: 73 · 2012: 89
- FWCI
- 12.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Genetics (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- National Institute of General Medical Sciences (GM-40282, R01GM040282)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- 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
- Keywords
- positive selection, likelihood model, HIV-1 envelope gene, V3 region, amino acid substitution rates, nonsynonymous substitutions, neutral model, viral evolution
- MeSH terms
- Amino Acids, Binding Sites, Codon, Electron Transport Complex IV, Humans, Models, Genetic, Peptide Fragments, Selection, Genetic, Models, Statistical, HIV-1, HIV Envelope Protein gp120, Likelihood Functions, Mutagenesis, Site-Directed, Evolution, Molecular
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