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doi:10.1534/genetics.105.047217
A more recent version of this article appeared on February 1, 2006.
REGULAR RESEARCH PAPERS |
Estimating selection on non-synonymous mutations
Laurence Loewe 1*, Brian Charlesworth 1, Carolina Bartolome 2 and Veronique Noel 1
1 Institute of Evolutionary Biology, University of Edinburgh
2 Universidade de Santiago de Compostela
* To whom correspondence should be addressed. E-mail: laurence.loewe{at}evolutionary-research.net.
Submitted on June 23, 2005
Revised on September 21, 2005
Accepted on 5 November 2005
The distribution of mutational effects on fitness is of fundamental importance for many aspects of evolution. We develop two methods for characterizing the fitness effects of deleterious, non-synonymous mutations, using polymorphism data from two related species. These methods also provide estimates of the proportion of amino-acid substitutions that are selectively favorable, when combined with data on between-species sequence divergence. The methods are applicable to species with different effective population sizes, but which share the same distribution of mutational effects. The first, simpler, method assumes that diversity for all non-neutral mutations is given by the value under mutation-selection balance, while the second method allows for stronger effects of genetic drift and yields estimates of the parameters of the probability distribution of mutational effects. We apply these methods to data on populations of Drosophila miranda and D. pseudoobscura, and find evidence for the presence of deleterious non-synonymous mutations, mostly with small heterozygous selection coefficients (a mean of the order of 1e-5 for segregating variants). A leptokurtic gamma distribution of mutational effects with a shape parameter between 0.1 and 1 can explain observed diversities, in the absence of a separate class of completely neutral non-synonymous mutations. We also describe a simple approximate method for estimating the harmonic mean selection coefficient from diversity data on a single species.
Key Words: Drosophila miranda Drosophila affinis, Drosophila pseudoobscura, advantageous mutations, deleterious mutations, distribution of mutational effects
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