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MBE Advance Access originally published online on January 14, 2008
Molecular Biology and Evolution 2008 25(6):1007-1015; 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 Articles

The McDonald–Kreitman Test and Slightly Deleterious Mutations

Jane Charlesworth* and Adam Eyre-Walker*,{dagger}

* Centre for the Study of Evolution, University of Sussex, Brighton, United Kingdom
{dagger} National Evolutionary Synthesis Center, Durham, New Hampshire

E-mail: a.c.eyre-walker{at}sussex.ac.uk

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 nonsilent polymorphisms and substitutions in a McDonald and Kreitman-type analysis. Unfortunately, this estimate of adaptive evolution is biased downward by the segregation of slightly deleterious mutations. It has been suggested that 1 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 although 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. The method is reasonably satisfactory, only if the rate of adaptive evolution is high and the distribution of fitness effects for slightly deleterious mutations is very leptokurtic. 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.

Key Words: adaptive evolution • neutral theory • deleterious mutations

John H. McDonald, Associate Editor


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