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Journals Genetics Volume 189 Issue 4

The distribution of fitness effects (DFE) of new mutations is of fundamental importance in evolutionary genetics. Recently, methods have been developed for inferring the DFE that use information from the allele frequency distributions of putatively neutral and selected nucleotide polymorphic variants in a population sample. Here, we extend an existing maximum-likelihood method that estimates the DFE under the assumption that mutational effects are unconditionally deleterious, by including a fraction of positively selected mutations. We allow one or more classes of positive selection coefficients in the model and estimate both the fraction of mutations that are advantageous and the strength of selection acting on them. We show by simulations that the method is capable of recovering the parameters of the DFE under a range of conditions. We apply the method to two data sets on multiple protein-coding genes from African populations of Drosophila melanogaster . We use a probabilistic reconstruction of the ancestral states of the polymorphic sites to distinguish between derived and ancestral states at polymorphic nucleotide sites. In both data sets, we see a significant improvement in the fit when a category of positively selected amino acid mutations is included, but no further improvement if additional categories are added. We estimate that between 1% and 2% of new nonsynonymous mutations in D. melanogaster are positively selected, with a scaled selection coefficient representing the product of the effective population size, N e , and the strength of selection on heterozygous carriers of ∼2.5. Received June 16, 2011. Accepted September 24, 2011. Copyright © 2011 by the Genetics Society of America « Previous | Next Article » Table of Contents This Article Published online before print September 27, 2011 , doi: 10.1534/genetics.111.131730 Genetics December 1, 2011 vol. 189 no. 4 1427-1437 » Abstract Full Text Full Text (PDF) Classifications Investigations Population and Evolutionary Genetics Services Email this article to a friend Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Download to citation manager Citing Articles Load citing article information Google Scholar Articles by Schneider, A. PubMed PubMed citation Articles by Schneider, A. Related Content Load related web page information This Months's Issue January 2012, 190 (1) Alert me to new issues of Genetics ABOUT SUBSCRIBE INFO FOR AUTHORS ONLINE SUBMISSION EDITORIAL BOARD CONTACT ALERTS HELP ADVERTISING RSS Help Contact Us International Access Link Print ISSN: 0016-6731 Online ISSN: 1943-2631 Copyright © 2012 by the Genetics Society of America phone: 412-268-1812 fax: 412-268-1813 email: genetics-gsa@andrew.cmu.edu

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A Method for Inferring the Rate of Occurrence and Fitness Effects of Advantageous Mutations

Schneider, Adrian; Charlesworth, Brian; Eyre-Walker, Adam; Keightley, Peter D.
Genetics , Volume 189 (4): 1427
Genetics Society of America – Dec 1, 2011

More Info
  • Publisher Genetics Society of America
  • Copyright Copyright © 2011 by the Genetics Society of America
  • ISSN 0016-6731
  • eISSN 1943-2631
  • D.O.I. 10.1534/genetics.111.131730
  • Publisher site Get PDF  

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