title: Estimating diversifying selection and functional constraint in the presence of recombination.
abstract: Models of molecular evolution that incorporate the ratio of nonsynonymous to synonymous polymorphism (dN/dS ratio) as a parameter can be used to identify sites that are under diversifying selection or functional constraint in a sample of gene sequences. However, when there has been recombination in the evolutionary history of the sequences, reconstructing a single phylogenetic tree is not appropriate, and inference based on a single tree can give misleading results. In the presence of high levels of recombination, the identification of sites experiencing diversifying selection can suffer from a false-positive rate as high as 90%. We present a model that uses a population genetics approximation to the coalescent with recombination and use reversible-jump MCMC to perform Bayesian inference on both the dN/dS ratio and the recombination rate, allowing each to vary along the sequence. We demonstrate that the method has the power to detect variation in the dN/dS ratio and the recombination rate and does not suffer from a high false-positive rate. We use the method to analyze the porB gene of Neisseria meningitidis and verify the inferences using prior sensitivity analysis and model criticism techniques.
authors.affiliation: Department of Statistics, University of Oxford, Oxford OX1 3TG, United Kingdom. daniel.wilson@sjc.ox.ac.uk
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Wilson
authors.forename: Gilean
authors.initials: G
authors.lastname: McVean
mesh_terms: D001499:Bayes Theorem; D003198:Computer Simulation; D005828:Genetics, Population; D006239:Haplotypes; D008957:Models, Genetic; D015233:Models, Statistical; D009345:Neisseria meningitidis / Q000235:genetics*; D011110:Polymorphism, Genetic; D018272:Porins / Q000235:genetics*; D011995:Recombination, Genetic; D012641:Selection, Genetic
chemical_list: D018272:Porins; C057699:porin protein, Neisseria