title: CodonTest: modeling amino acid substitution preferences in coding sequences.
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 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 rate classes, where 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.
authors.affiliation: Department of Pathology, University of California, San Diego, La Jolla, California, United States of America.
authors.forename: Wayne
authors.initials: W
authors.lastname: Delport
authors.forename: Konrad
authors.initials: K
authors.lastname: Scheffler
authors.forename: Gordon
authors.initials: G
authors.lastname: Botha
authors.forename: Mike B
authors.initials: MB
authors.lastname: Gravenor
authors.forename: Spencer V
authors.initials: SV
authors.lastname: Muse
authors.forename: Sergei L
authors.initials: SL
authors.lastname: Kosakovsky Pond
mesh_terms: D000465:Algorithms; D019943:Amino Acid Substitution / Q000235:genetics*; D003062:Codon; D003198:Computer Simulation; D004259:DNA-Directed DNA Polymerase / Q000235:genetics; D019143:Evolution, Molecular; D015497:HIV-1 / Q000235:genetics; D006388:Hemagglutinins / Q000235:genetics; D006801:Humans; D008390:Markov Chains; D008957:Models, Genetic; D016415:Sequence Alignment
chemical_list: D003062:Codon; D006388:Hemagglutinins; D004259:DNA-Directed DNA Polymerase
references.citation: J Mol Evol. 1985;22(2):160-74
references.pmid: 3934395
references.citation: Mol Biol Evol. 2009 May;26(5):1155-61
references.pmid: 19233963
references.citation: Bioinformatics. 1998;14(9):817-8
references.pmid: 9918953
references.citation: Bioinformatics. 2005 Mar 1;21(5):676-9
references.pmid: 15509596
references.citation: Mol Biol Evol. 1994 Sep;11(5):715-24
references.pmid: 7968485
references.citation: Comput Appl Biosci. 1992 Jun;8(3):275-82
references.pmid: 1633570
references.citation: Mol Biol Evol. 1994 Sep;11(5):725-36
references.pmid: 7968486
references.citation: Bioinformatics. 2005 May 15;21(10):2531-3
references.pmid: 15713735
references.citation: J Virol. 2008 Jan;82(2):596-601
references.pmid: 17942553
references.citation: J Mol Evol. 1996 Apr;42(4):459-68
references.pmid: 8642615
references.citation: Genetics. 2004 Aug;167(4):2027-43
references.pmid: 15342538
references.citation: J Mol Evol. 1981;17(6):368-76
references.pmid: 7288891
references.citation: PLoS Pathog. 2007 Jul;3(7):e94
references.pmid: 17616974
references.citation: Nucleic Acids Res. 2006 Jan 1;34(Database issue):D327-31
references.pmid: 16381879
references.citation: Mol Biol Evol. 2009 Feb;26(2):255-71
references.pmid: 18922761
references.citation: Mol Biol Evol. 2007 Jan;24(1):159-70
references.pmid: 17038448
references.citation: Science. 2008 Apr 18;320(5874):340-6
references.pmid: 18420927
references.citation: PLoS One. 2010 Jul 21;5(7):e11587
references.pmid: 20657773
references.citation: Mol Biol Evol. 2005 Dec;22(12):2375-85
references.pmid: 16107593
references.citation: Mol Phylogenet Evol. 2007 Feb;42(2):298-307
references.pmid: 16942891
references.citation: Mol Biol Evol. 2008 Jul;25(7):1253-6
references.pmid: 18397919
references.citation: BMC Bioinformatics. 2006 Mar 16;7:148
references.pmid: 16542458
references.citation: Mol Biol Evol. 2009 Jul;26(7):1663-76
references.pmid: 19383983
references.citation: PLoS Comput Biol. 2007 Nov;3(11):e231
references.pmid: 18039027
references.citation: Proteins. 1997 Jul;28(3):405-20
references.pmid: 9223186
references.citation: Mol Biol Evol. 2008 Jul;25(7):1307-20
references.pmid: 18367465
references.citation: J Mol Evol. 2002 Jul;55(1):65-73
references.pmid: 12165843
references.citation: J Mol Evol. 2000 Apr;50(4):348-58
references.pmid: 10795826
references.citation: Mol Biol Evol. 1987 Jul;4(4):406-25
references.pmid: 3447015
references.citation: Mol Biol Evol. 2005 May;22(5):1208-22
references.pmid: 15703242
references.citation: Mol Biol Evol. 2007 Jul;24(7):1464-79
references.pmid: 17400572
references.citation: Mol Biol Evol. 2000 Jun;17(6):890-6
references.pmid: 10833195
references.citation: Mol Biol Evol. 2006 Oct;23(10):1891-901
references.pmid: 16818476
references.citation: Nat Med. 2004 Mar;10(3):282-9
references.pmid: 14770175
references.citation: J Mol Evol. 2005 Mar;60(3):315-26
references.pmid: 15871042
references.citation: Brief Bioinform. 2009 Jan;10(1):97-109
references.pmid: 18971241
references.citation: PLoS Comput Biol. 2009 Nov;5(11):e1000581
references.pmid: 19956739
references.citation: J Virol. 2008 Jul;82(13):6434-46
references.pmid: 18434400
references.citation: Mol Biol Evol. 2001 May;18(5):691-9
references.pmid: 11319253
references.citation: Mol Biol Evol. 2007 Feb;24(2):388-97
references.pmid: 17110464
references.citation: Syst Biol. 2003 Oct;52(5):696-704
references.pmid: 14530136
references.citation: Genetics. 2000 May;155(1):431-49
references.pmid: 10790415
references.citation: PLoS One. 2007 Jun 06;2(6):e503
references.pmid: 17551583
references.citation: Philos Trans R Soc Lond B Biol Sci. 2008 Dec 27;363(1512):3941-53
references.pmid: 18852098
references.citation: PLoS One. 2010 Jul 30;5(7):e11230
references.pmid: 20689581
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13480-5
references.pmid: 18768804
references.citation: J Theor Biol. 1996 Nov 21;183(2):195-205
references.pmid: 8977877
references.citation: Mol Biol Evol. 2010 Mar;27(3):520-36
references.pmid: 19864470
references.citation: Mol Biol Evol. 2005 Mar;22(3):478-85
references.pmid: 15509724
references.citation: Mol Biol Evol. 1993 Nov;10(6):1396-401
references.pmid: 8277861