CoChat
Sign Up
Cited by 1,374Evolution and Genetic DynamicsGenomics and Phylogenetic StudiesRNA and protein synthesis mechanisms

Codon-substitution models for detecting molecular adaptation at individual sites along specific lineages

Yang, Ziheng, Nielsen, Rasmus·2002·Molecular Biology and Evolution
DOI 10.1093/oxfordjournals.molbev.a004148
Open this paper in CoChat — free account

Abstract

The nonsynonymous (amino acid-altering) to synonymous (silent) substitution rate ratio (omega = d(N)/d(S)) provides a measure of natural selection at the protein level, with omega = 1, >1, and <1, indicating neutral evolution, purifying selection, and positive selection, respectively. Previous studies that used this measure to detect positive selection have often taken an approach of pairwise comparison, estimating substitution rates by averaging over all sites in the protein. As most amino acids in a functional protein are under structural and functional constraints and adaptive evolution probably affects only a few sites at a few time points, this approach of averaging rates over sites and over time has little power. Previously, we developed codon-based substitution models that allow the omega ratio to vary either among lineages or among sites. In this paper we extend previous models to allow the omega ratio to vary both among sites and among lineages and implement the new models in the likelihood framework. These models may be useful for identifying positive selection along prespecified lineages that affects only a few sites in the protein. We apply those branch-site models as well as previous branch- and site-specific models to three data sets: the lysozyme genes from primates, the tumor suppressor BRCA1 genes from primates, and the phytochrome (PHY) gene family in angiosperms. Positive selection is detected in the lysozyme and BRCA genes by both the new and the old models. However, only the new models detected positive selection acting on lineages after gene duplication in the PHY gene family. Additional tests on several data sets suggest that the new models may be useful in detecting positive selection after gene duplication in gene family evolution.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1093/oxfordjournals.molbev.a004148

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • RELAX builds upon the random effects branch-site (BS-REL) models, which were developed to overcome statistical and methodological restrictions imposed by the popular branch-site class of evolutionary models.

    “It builds upon the random effects branch-site (BS-REL) models (Kosakovsky Pond et al. 2011), which were developed to overcome statistical and methodological restrictions imposed by the popular”

    From RELAX: Detecting Relaxed Selection in a Phylogenetic Framework (2015) · cites this paper as Yang and Nielsen 2002

    The Introduction (page not available) describes this paper’s branch-site models, and the Theory section states assumptions they impose. The copy does not address RELAX or BS-REL, so it cannot establish that RELAX builds on BS-REL or that BS-REL was developed to overcome restrictions of these models. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • The introduction of branch-site models addressed evolutionary rate variation not only over sites but also over branches.

    “The introduction of branch-site models addressed evolutionary rate variation not only over sites but also over branches (Yang and Nielsen 2002).”

    From RELAX: Detecting Relaxed Selection in a Phylogenetic Framework (2015) · cites this paper as Yang and Nielsen 2002

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 4

  1. Anisimova, M., J. P. Bielawski and Z. Yang. 2001. The accuracy and power of likelihood ratio tests to detect positive selection at amino acid sites. Mol. Biol. Evol. in press.
  2. Bishop, J. G., A. M. Dean and T. Mitchell-Olds. 2000. Rapid evolution in plant chitinases: molecular targets of selection in plant-pathogen coevolution. Proc. Natl. Acad. Sci. U.S.A. 97:5322-5327.
  3. Gillespie, J. H. 1991. The causes of molecular evolution. Oxford University Press, Oxford.
  4. Swanson, W. J., Z. Yang, M. F. Wolfner and C. F. Aquadro. 2001. Positive Darwinian selection in the evolution of mammalian female reproductive proteins. Proc. Natl. Acad. Sci. U.S.A. 98:25092514.

Cited by

Sorted by citations

Authors
Yang, Z., & Nielsen, R.
Affiliations
University College London (GB)
ORCID
Venue
Molecular Biology and Evolution
Publisher
Oxford University Press (OUP)
Published
2002-06-01
Volume
19
Issue
6
Pages
908-917
ISSN
  • 0737-4038 (ISSN-L)
  • 1537-1719
DOI
10.1093/oxfordjournals.molbev.a004148
OpenAlex
W2029549914
Cited by
1,374
References
1
Citations by year
2026: 39 · 2025: 27 · 2024: 66 · 2023: 57 · 2022: 50 · 2021: 67 · 2020: 71 · 2019: 63 · 2018: 50 · 2017: 63 · 2016: 42 · 2015: 48 · 2014: 72 · 2013: 52 · 2012: 78
FWCI
20.97
Type
journal article
Language
en
Open access
closed
Locations
  • Molecular Biology and Evolution (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • National Science Foundation
  • Biotechnology and Biological Sciences Research Council
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
codon substitution models, positive selection, branch-site model, site-specific selection, lineage-specific selection, dN/dS ratio, purifying selection, lysozyme, BRCA1, phytochrome, gene duplication, protein evolution, likelihood-based models
MeSH terms
Animals, Codon, Multigene Family, Humans, Models, Genetic, Muramidase, Mutation, Phylogeny, Phytochrome, Primates, Likelihood Functions, Evolution, Molecular, Genes, BRCA1, Magnoliopsida

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review