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Originally published as Genetics Published Articles Ahead of Print on November 19, 2005.

Genetics, Vol. 172, 1079-1092, February 2006, Copyright © 2006
doi:10.1534/genetics.105.047217

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Estimating Selection on Nonsynonymous Mutations

Laurence Loewe1, Brian Charlesworth, Carolina Bartolomé2 and Véronique Nöel

Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3JT, United Kingdom

1 Corresponding author: Institute of Evolutionary Biology, School of Biological Sciences, Ashworth Laboratories, University of Edinburgh, King's Bldgs., Edinburgh EH9 3JT, United Kingdom.
E-mail: laurence.loewe{at}evolutionary-research.net

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, nonsynonymous 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 that share the same distribution of mutational effects. The first, simpler, method assumes that diversity for all nonneutral 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 nonsynonymous mutations, mostly with small heterozygous selection coefficients (a mean of the order of 10–5 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 nonsynonymous mutations. We also describe a simple approximate method for estimating the harmonic mean selection coefficient from diversity data on a single species.




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