Document Detail

A comparison of models to infer the distribution of fitness effects of new mutations.
MedLine Citation:
PMID:  23341416     Owner:  NLM     Status:  MEDLINE    
Knowing the distribution of fitness effects (DFE) of new mutations is important for several topics in evolutionary genetics. Existing computational methods with which to infer the DFE based on DNA polymorphism data have frequently assumed that the DFE can be approximated by a unimodal distribution, such as a lognormal or a gamma distribution. However, if the true DFE departs substantially from the assumed distribution (e.g., if the DFE is multimodal), this could lead to misleading inferences about its properties. We conducted simulations to test the performance of parametric and nonparametric discretized distribution models to infer the properties of the DFE for cases in which the true DFE is unimodal, bimodal, or multimodal. We found that lognormal and gamma distribution models can perform poorly in recovering the properties of the distribution if the true DFE is bimodal or multimodal, whereas discretized distribution models perform better. If there is a sufficient amount of data, the discretized models can detect a multimodal DFE and can accurately infer the mean effect and the average fixation probability of a new deleterious mutation. We fitted several models for the DFE of amino acid-changing mutations using whole-genome polymorphism data from Drosophila melanogaster and the house mouse subspecies Mus musculus castaneus. A lognormal DFE best explains the data for D. melanogaster, whereas we find evidence for a bimodal DFE in M. m. castaneus.
Athanasios Kousathanas; Peter D Keightley
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-22
Journal Detail:
Title:  Genetics     Volume:  193     ISSN:  1943-2631     ISO Abbreviation:  Genetics     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-02     Completed Date:  2013-11-27     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  0374636     Medline TA:  Genetics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1197-208     Citation Subset:  IM    
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MeSH Terms
Drosophila melanogaster / genetics
Gene Frequency*
Genetic Fitness*
Models, Genetic*
Mutation, Missense*
Polymorphism, Genetic
Population / genetics
Grant Support
//Biotechnology and Biological Sciences Research Council; //Wellcome Trust

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