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MBE Advance Access originally published online on November 13, 2007
Molecular Biology and Evolution 2007 24(12):2687-2697; doi:10.1093/molbev/msm196
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© The Author 2007. 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

Patterns of Mutation and Selection at Synonymous Sites in Drosophila

Nadia D. Singh*, Vanessa L. Bauer DuMont*, Melissa J. Hubisz{dagger}, Rasmus Nielsen{ddagger} and Charles F. Aquadro*

* Department of Molecular Biology and Genetics, Cornell University, Ithaca
{dagger} Department of Human Genetics, University of Chicago
{ddagger} Institute of Biology and Centre for Bioinformatics, University of Copenhagen, Copenhagen, Denmark

E-mail: nds25{at}cornell.edu.

Accepted for publication September 7, 2007.

That natural selection affects molecular evolution at synonymous sites in protein-coding sequences is well established and is thought to predominantly reflect selection for translational efficiency/accuracy mediated through codon bias. However, a recently developed maximum likelihood framework, when applied to 18 coding sequences in 3 species of Drosophila, confirmed an earlier report that the Notch gene in Drosophila melanogaster was evolving under selection in favor of those codons defined as unpreferred in this species. This finding opened the possibility that synonymous sites may be subject to a variety of selective pressures beyond weak selection for increased frequencies of the codons currently defined as "preferred" in D. melanogaster. To further explore patterns of synonymous site evolution in Drosophila in a lineage-specific manner, we expanded the application of the maximum likelihood framework to 8,452 protein coding sequences with well-defined orthology in D. melanogaster, Drosophila sechellia, and Drosophila yakuba. Our analyses reveal intragenomic and interspecific variation in mutational patterns as well as in patterns and intensity of selection on synonymous sites. In D. melanogaster, our results provide little statistical evidence for recent selection on synonymous sites, and Notch remains an outlier. In contrast, in D. sechellia our findings provide evidence in support of selection predominantly in favor of preferred codons. However, there is a small subset of genes in this species that appear to be evolving under selection in favor of unpreferred codons, which indicates that selection on synonymous sites is not limited to the preferential fixation of mutations that enhance the speed or accuracy of translation in this species.

Key Words: synonymous site • codon bias • mutational patterns


Spencer Muse, Associate Editor


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