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MBE Advance Access published online on October 8, 2008
Molecular Biology and Evolution, doi:10.1093/molbev/msn224
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© 2008 The Authors
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Letter

Uncorrected nucleotide bias in mtDNA can mimic the effects of positive Darwinian selection

Mihai Albu1, Xiang Jia Min2,3, Donal Hickey3 and Brian Golding1

1 Department of Biology. McMaster University, 1280 Main Street West, Hamilton, Ontario, L8S 4K1
2 Department of Biological Sciences, Youngstown State University, Youngstown, OH 44555
3 Department of Biology, Concordia University, Montréal, Québec, H3G 1M8

Corresponding author: Brian Golding, Tel: 905-525-9140, Fax: 905-522-6066, Email: Golding{at}McMaster.CA

Received for publication August 6, 2008. Revision received September 29, 2008. Accepted for publication September 30, 2008.

The relative rates of nucleotide substitution at synonymous and non-synonymous sites within protein coding regions have been widely used to infer the action of natural selection from comparative sequence data. It is known, however, that mutational and repair biases can affect rates of evolution at both synonymous and non-synonymous sites. More importantly, it is also known that synonymous sites are particularly prone to the effects of nucleotide bias. This means that nucleotide biases may affect the calculated ratio of substitution rates at synonymous and non-synonymous sites. Using a large dataset of animal mitochondrial sequences, we demonstrate that this is, in fact, the case. Highly biased nucleotide sequences are characterized by significantly elevated dN/dS ratios, but only when the nucleotide frequencies are not taken into account. When the analysis is repeated taking the nucleotide frequencies at each codon position into account, such elevated ratios disappear. These results suggest that the recently reported differences in dN/dS ratios between vertebrate and invertebrate mitochondrial sequences could be explained by variations in mitochondrial nucleotide frequencies rather than the effects of positive Darwinian selection.

Key Words: dN/dS ratios • nucleotide bias • synonymous sites • nonsynonymous sites • PAML • CODEML • mtDNA


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[Abstract] [Full Text] [PDF]


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