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MBE Advance Access originally published online on July 30, 2008
Molecular Biology and Evolution 2008 25(10):2199-2209; doi:10.1093/molbev/msn166
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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

Synonymous and Nonsynonymous Polymorphisms versus Divergences in Bacterial Genomes

Austin L. Hughes, Robert Friedman, Pierre Rivailler and Jeffrey O. French

Department of Biological Sciences, University of South Carolina

E-mail: austin{at}biol.sc.edu.

Accepted for publication July 24, 2008.

Comparison of the ratio of nonsynonymous to synonymous polymorphisms within species with the ratio of nonsynonymous to synonymous substitutions between species has been widely used as a supposed indicator of positive Darwinian selection, with the ratio of these 2 ratios being designated as a neutrality index (NI). Comparison of genome-wide polymorphism within 12 species of bacteria with divergence from an outgroup species showed substantial differences in NI among taxa. A low level of nonsynonymous polymorphism at a locus was the best predictor of NI < 1, rather than a high level of nonsynonymous substitution between species. Moreover, genes with NI < 1 showed a strong tendency toward the occurrence of rare nonsynonymous polymorphisms, as expected under the action of ongoing purifying selection. Thus, our results are more consistent with the hypothesis that a high relative rate of between-species nonsynonymous substitution reflects mainly the action of purifying selection within species to eliminate slightly deleterious mutations rather than positive selection between species. This conclusion is consistent with previous results highlighting an important role of slightly deleterious variants in bacterial evolution and suggests caution in the use of the McDonald–Kreitman test and related statistics as tests of positive selection.

Key Words: bacterial evolution • homologous recombination • McDonald–Kreitman test • neutrality index • nucleotide substitution

Dan Graur, Associate Editor


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