An Improved General Amino Acid Replacement Matrix
Open accessAbstract
Amino acid replacement matrices are an essential basis of protein phylogenetics. They are used to compute substitution probabilities along phylogeny branches and thus the likelihood of the data. They are also essential in protein alignment. A number of replacement matrices and methods to estimate these matrices from protein alignments have been proposed since the seminal work of Dayhoff et al. (1972). An important advance was achieved by Whelan and Goldman (2001) and their WAG matrix, thanks to an efficient maximum likelihood estimation approach that accounts for the phylogenies of sequences within each training alignment. We further refine this method by incorporating the variability of evolutionary rates across sites in the matrix estimation and using a much larger and diverse database than BRKALN, which was used to estimate WAG. To estimate our new matrix (called LG after the authors), we use an adaptation of the XRATE software and 3,912 alignments from Pfam, comprising approximately 50,000 sequences and approximately 6.5 million residues overall. To evaluate the LG performance, we use an independent sample consisting of 59 alignments from TreeBase and randomly divide Pfam alignments into 3,412 training and 500 test alignments. The comparison with WAG and JTT shows a clear likelihood improvement. With TreeBase, we find that 1) the average Akaike information criterion gain per site is 0.25 and 0.42, when compared with WAG and JTT, respectively; 2) LG is significantly better than WAG for 38 alignments (among 59), and significantly worse with 2 alignments only; and 3) tree topologies inferred with LG, WAG, and JTT frequently differ, indicating that using LG impacts not only the likelihood value but also the output tree. Results with the test alignments from Pfam are analogous. LG and a PHYML implementation can be downloaded from http://atgc.lirmm.fr/LG.
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Analyzing the Moroz-3D dataset using the site-homogeneous LG model yielded a different tree with a better likelihood score than the WAG tree, uniting demosponges and glass sponges as the sister group of all other animals, followed by ctenophores and then by calcareous and homoscleromorph sponges, with very low statistical support.
“analyzing the Moroz-3D dataset using the similar but generally better-fitting site-homogeneous Le and Gascuel (LG) model (44), we found a different tree with a better likelihood score (Fig. S2 A ). This tree united demosponges and glass sponges as the sister group of all other animals, followed by ctenophores and then by calcareous and homoscleromorph sponges. Although statistical support for this”
From Genomic data do not support comb jellies as the sister group to all other animals (2015) · cites this paper as [44]
Models previously used to study animal phylogeny (WAG+G, LG+G, GTR+G, PF-schemes, CAT-GTR+G) fell short of adequately describing among-site amino acid preferences in both WhelanD20 and Chang datasets.
“We showed that for both datasets, models that have previously been used to study the animal phylogeny fell short, to various degrees, of adequately describing among-site amino acid preferences”
From Improved Modeling of Compositional Heterogeneity Supports Sponges as Sister to All Other Animals (2017) · cites this paper as [22]
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BackgroundDecomposing information into copying versus transformation
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- Authors
- Le, S. Q., & Gascuel, O.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- ORCID
- Venue
- Molecular Biology and Evolution
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-04-03
- Volume
- 25
- Issue
- 7
- Pages
- 1307-1320
- ISSN
- 0737-4038 (ISSN-L)
- 1537-1719
- OpenAlex
- W2163627198
- Cited by
- 3,127
- References
- 4
- Citations by year
- 2026: 142 · 2025: 167 · 2024: 213 · 2023: 211 · 2022: 209 · 2021: 289 · 2020: 252 · 2019: 279 · 2018: 213 · 2017: 201 · 2016: 189 · 2015: 156 · 2014: 168 · 2013: 126 · 2012: 88
- FWCI
- 30.19
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- Locations
- Molecular Biology and Evolution (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Funders
- Agence Nationale de la Recherche
- 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 › Molecular Biology › Fractal and DNA sequence analysis
- Keywords
- site rate heterogeneity, maximum likelihood estimation, protein sequence alignment
- MeSH terms
- Amino Acid Sequence, Models, Genetic, Molecular Sequence Data, Phylogeny, Software, Sequence Alignment, Evolution, Molecular, Computational Biology, Sequence Analysis, Protein, Databases, Nucleic Acid
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