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MBE Advance Access published online on October 13, 2006
Molecular Biology and Evolution, doi:10.1093/molbev/msl146
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© The Author 2006. 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
Accepted October 10, 2006

Research Article

Research Article: Maximum Likelihood Estimation of Ancestral Codon Usage Bias Parameters in Drosophila

Rasmus Nielsen 1 *, Vanessa L. Bauer DuMont 2, Melissa J. Hubisz 3, and Charles F. Aquadro 2

1 Institute of Biology and Centre for Bioinformatics, University of Copenhagen, Universitetsparken 15, 2100 Kbh Ø, Denmark; Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY 14853, USA
2 Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA
3 Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, NY 14853, USA

* To whom correspondence should be addressed.
Rasmus Nielsen, E-mail: rasmus{at}binf.ku.dk


  Abstract

We present a likelihood method for estimating codon usage bias parameters along the lineages of a phylogeny. The method is an extension of the classical codon based models used for estimating dN/dS ratios along the lineages of a phylogeny. However, we add one extra parameter for each lineage: the selection coefficient for optimal codon usage (S), allowing joint maximum likelihood estimation of S and the dN/dS ratio. We apply the method to previously published data from Drosophila melanogaster, D. simulans and D. yakuba and show, in accordance with previous results, that the D. melanogaster lineage has experienced a reduction in the selection for optimal codon usage. However, the D. melanogaster lineage has also experienced a change in the biological mutation rates relative to D. simulans, in particular a relative reduction in the mutation rate from A to G and an increase in the mutation rate from C to T. However, neither a reduction in the strength of selection, nor a change in the mutational pattern can alone explain all of the data observed in the D. melanogaster lineage. For example, we also confirm previous results showing that the Notch locus has experienced positive selection for previously classified unpreferred mutations.

Keywords: codon usage bias; codon usage; maximum likelihood; codon based models; selection.
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