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dc.contributor.authorTamuri, AUen_US
dc.contributor.authordos Reis, Men_US
dc.contributor.authorGoldstein, RAen_US
dc.date.accessioned2016-09-05T14:21:27Z
dc.date.issued2012-03en_US
dc.date.submitted2016-07-22T19:17:11.732Z
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/14968
dc.description.abstractEstimation of the distribution of selection coefficients of mutations is a long-standing issue in molecular evolution. In addition to population-based methods, the distribution can be estimated from DNA sequence data by phylogenetic-based models. Previous models have generally found unimodal distributions where the probability mass is concentrated between mildly deleterious and nearly neutral mutations. Here we use a sitewise mutation-selection phylogenetic model to estimate the distribution of selection coefficients among novel and fixed mutations (substitutions) in a data set of 244 mammalian mitochondrial genomes and a set of 401 PB2 proteins from influenza. We find a bimodal distribution of selection coefficients for novel mutations in both the mitochondrial data set and for the influenza protein evolving in its natural reservoir, birds. Most of the mutations are strongly deleterious with the rest of the probability mass concentrated around mildly deleterious to neutral mutations. The distribution of the coefficients among substitutions is unimodal and symmetrical around nearly neutral substitutions for both data sets at adaptive equilibrium. About 0.5% of the nonsynonymous mutations and 14% of the nonsynonymous substitutions in the mitochondrial proteins are advantageous, with 0.5% and 24% observed for the influenza protein. Following a host shift of influenza from birds to humans, however, we find among novel mutations in PB2 a trimodal distribution with a small mode of advantageous mutations.en_US
dc.description.sponsorshipA.U.T. is supported by a studentship grant from the Wellcome Trust, United Kingdom. M.d.R. is supported by a research grant awarded to Ziheng Yang by the Biotechnology and Biological Sciences Research Council, United Kingdom. R.A.G. is supported by the Medical Research Council, United Kingdom.en_US
dc.format.extent1101 - 1115en_US
dc.languageengen_US
dc.relation.ispartofGeneticsen_US
dc.rights“Original publication is available at http://www.genetics.org/content/190/3/1101.article-info”
dc.subjectAlgorithmsen_US
dc.subjectAnimalsen_US
dc.subjectComputer Simulationen_US
dc.subjectEvolution, Molecularen_US
dc.subjectGenetic Driften_US
dc.subjectHumansen_US
dc.subjectModels, Geneticen_US
dc.subjectMutationen_US
dc.subjectPhylogenyen_US
dc.subjectReproducibility of Resultsen_US
dc.subjectSelection, Geneticen_US
dc.titleEstimating the distribution of selection coefficients from phylogenetic data using sitewise mutation-selection models.en_US
dc.typeArticle
dc.rights.holderCopyright © 2012 by the Genetics Society of America Available freely online through the author-supported open access option.
dc.identifier.doi10.1534/genetics.111.136432en_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/22209901en_US
pubs.issue3en_US
pubs.notesNot knownen_US
pubs.publication-statusPublisheden_US
pubs.volume190en_US


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