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MBE Advance Access published online on January 14, 2008
Molecular Biology and Evolution, doi:10.1093/molbev/msn005
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© The Author 2008. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Research Article

The McDonald-Kreitman Test and Slightly Deleterious Mutations

Jane Charlesworth1 and Adam Eyre-Walker1,2,3

1 Centre for the Study of Evolution, University of Sussex, Brighton, BN1 9QG, United Kingdom
2 National Evolutionary Synthesis Center, Durham, NC 27705, USA

3 Correspondence : a.c.eyre-walker{at}sussex.ac.uk

Received for publication September 11, 2007. Revision received December 10, 2007. Accepted for publication December 15, 2007.

It is possible to estimate the proportion of substitutions that are due to adaptive evolution using the numbers of silent and non-silent polymorphisms and substitutions in a McDonald and Kreitman type analysis. Unfortunately this estimate of adaptive evolution is biased downwards by the segregation of slightly deleterious mutations. It has been suggested that one way to cope with the effects of these slightly deleterious mutations is to remove low frequency polymorphisms from the analysis. We investigate the performance of this method theoretically. We show that whilst removing low frequency polymorphisms does indeed reduce the bias in the estimate of adaptive evolution, the estimate is always downwardly biased, often to the extent that one would not be able to detect adaptive evolution, even if it existed. Only if rates of adaptive evolution are high and the distribution of fitness effects for slightly deleterious mutations is very leptokurtic, is the method reasonably satisfactory. Our analysis suggests that adaptive evolution could be quite prevalent in humans (> 8%) and still not be detectable using current methodologies. Our analysis also suggests that the level of adaptive evolution has probably been underestimated, possibly substantially, in both bacteria and Drosophila.


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