Sep 29, 2011

A method for inferring the rate of occurrence and fitness effects of advantageous mutations

Genetics
Adrian SchneiderPeter D Keightley

Abstract

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 ami...Continue Reading

Mentioned in this Paper

Likelihood Functions
Nucleotides
Alleles
Genetic Polymorphism
Drosophila melanogaster
Positive Selection
Amino Acid [EPC]
Metazoa
Selection, Genetic

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