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    CodonTest: Modeling amino acid substitution preferences in coding sequences

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    CodonTest modeling amino acid ...
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    Genre
    Journal Article
    Date
    2010-08-01
    Author
    Delport, W
    Scheffler, K
    Botha, G
    Gravenor, MB
    Muse, SV
    Kosakovsky Pond, SLK
    Subject
    Algorithms
    Amino Acid Substitution
    Codon
    Computer Simulation
    DNA-Directed DNA Polymerase
    Evolution, Molecular
    HIV-1
    Hemagglutinins
    Humans
    Markov Chains
    Models, Genetic
    Sequence Alignment
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    Permanent link to this record
    http://hdl.handle.net/20.500.12613/5538
    
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    DOI
    10.1371/journal.pcbi.1000885
    Abstract
    Codon models of evolution have facilitated the interpretation of selective forces operating on genomes. These models, however, assume a single rate of non-synonymous substitution irrespective of the nature of amino acids being exchanged. Recent developments have shown that models which allow for amino acid pairs to have independent rates of substitution offer improved fit over single rate models. However, these approaches have been limited by the necessity for large alignments in their estimation. An alternative approach is to assume that substitution rates between amino acid pairs can be subdivided into K rate classes, dependent on the information content of the alignment. However, given the combinatorially large number of such models, an efficient model search strategy is needed. Here we develop a Genetic Algorithm (GA) method for the estimation of such models. A GA is used to assign amino acid substitution pairs to a series of K rate classes, where K is estimated from the alignment. Other parameters of the phylogenetic Markov model, including substitution rates, character frequencies and branch lengths are estimated using standard maximum likelihood optimization procedures. We apply the GA to empirical alignments and show improved model fit over existing models of codon evolution. Our results suggest that current models are poor approximations of protein evolution and thus gene and organism specific multi-rate models that incorporate amino acid substitution biases are preferred. We further anticipate that the clustering of amino acid substitution rates into classes will be biologically informative, such that genes with similar functions exhibit similar clustering, and hence this clustering will be useful for the evolutionary fingerprinting of genes. © 2010 Delport et al.
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    Public Library of Science (PLoS)
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    PLoS Computational Biology
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    http://dx.doi.org/10.34944/dspace/5520
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