title: Bayesian estimation of nonsynonymous/synonymous rate ratios for pairwise sequence comparisons.
abstract: The nonsynonymous/synonymous rate ratio (ω = d(N)/d(S)) is an important measure of the mode and strength of natural selection acting on nonsynonymous mutations in protein-coding genes. The simplest such analysis is the estimation of the d(N)/d(S) ratio using two sequences. Both heuristic counting methods and the maximum-likelihood (ML) method based on a codon substitution model are widely used for such analysis. However, these methods do not have nice statistical properties, as the estimates can be zero or infinity in some data sets, so that their means and variances are infinite. In large genome-scale comparisons, such extreme estimates (either 0 or ∞) of ω and sequence distance (t) are common. Here, we implement a Bayesian method to estimate ω and t in pairwise sequence comparisons. Using a combination of computer simulation and real data analysis, we show that the Bayesian estimates have better statistical properties than the ML estimates, because the prior on ω and t shrinks the posterior of those parameters away from extreme values. We also calculate the posterior probability for ω > 1 as a Bayesian alternative to the likelihood ratio test. The new method is computationally efficient and may be useful for genome-scale comparisons of protein-coding gene sequences.
authors.affiliation: Department of Genetics, Evolution and Environment, University College London, London, United Kingdom.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Angelis
authors.affiliation: Department of Genetics, Evolution and Environment, University College London, London, United Kingdom.
authors.forename: Mario
authors.initials: M
authors.lastname: Dos Reis
authors.affiliation: Department of Genetics, Evolution and Environment, University College London, London, United Kingdom z.yang@ucl.ac.uk.
authors.forename: Ziheng
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000465:Algorithms; D000818:Animals; D001499:Bayes Theorem; D003198:Computer Simulation; D016678:Genome; D006801:Humans; D008322:Mammals / Q000235:genetics*; D012641:Selection, Genetic; D016415:Sequence Alignment
keywords: Bayesian estimation; evolutionary distance; nonsynonymous/synonymous rate ratio; pairwise comparisons; protein-coding sequences
references.citation: BMC Genomics. 2008 Jun 30;9:312
references.pmid: 18590545
references.citation: Proc Biol Sci. 2012 Sep 7;279(1742):3491-500
references.pmid: 22628470
references.citation: BMC Evol Biol. 2012 Jan 20;12:8
references.pmid: 22264329
references.citation: J Mol Evol. 1998 Apr;46(4):409-18
references.pmid: 9541535
references.citation: Mol Biol Evol. 1985 Mar;2(2):150-74
references.pmid: 3916709
references.citation: Infect Genet Evol. 2013 Jul;17:123-31
references.pmid: 23583792
references.citation: Mol Biol Evol. 1998 May;15(5):568-73
references.pmid: 9580986
references.citation: PLoS Pathog. 2013;9(11):e1003766
references.pmid: 24244173
references.citation: Nature. 1977 May 19;267(5608):275-6
references.pmid: 865622
references.citation: Gene. 2013 Apr 10;518(1):187-93
references.pmid: 23219994
references.citation: J Mol Evol. 2011 Feb;72(2):222-31
references.pmid: 21188366
references.citation: PLoS Biol. 2005 Jun;3(6):e170
references.pmid: 15869325
references.citation: Mol Ecol. 2003 May;12(5):1195-206
references.pmid: 12694283
references.citation: Mol Biol Evol. 1994 Sep;11(5):725-36
references.pmid: 7968486
references.citation: Comp Funct Genomics. 2008;:879023
references.pmid: 18551181
references.citation: Mol Biol Evol. 2000 Jan;17(1):32-43
references.pmid: 10666704
references.citation: Mol Biol Evol. 2010 Sep;27(9):2000-13
references.pmid: 20375075
references.citation: Mol Biol Evol. 2007 Aug;24(8):1586-91
references.pmid: 17483113
references.citation: Mol Biol Evol. 2006 Dec;23(12):2279-82
references.pmid: 16982818
references.citation: Nature. 1997 Jan 9;385(6612):151-4
references.pmid: 8990116
references.citation: Mol Ecol. 2013 Dec;22(23):5908-21
references.pmid: 24118210
references.citation: Mol Biol Evol. 1986 Sep;3(5):418-26
references.pmid: 3444411
references.citation: Genome Res. 2002 Apr;12(4):656-64
references.pmid: 11932250
references.citation: BMC Genomics. 2011 Jul 18;12:370
references.pmid: 21767398