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MBE Advance Access published online on July 21, 2007
Molecular Biology and Evolution, doi:10.1093/molbev/msm147
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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 Article

Relative Rates of Evolution in the Coding and Control Regions of African mtDNAs

Neil Howell*,{dagger}, Joanna L. Elson{ddagger}, Corinna Howell§ and Douglass M. Turnbull{ddagger}

* MIGENIX Corp., San Diego, California
{dagger} Department of Radiation Oncology, The University of Texas Medical Branch, Galveston
{ddagger} Mitochondrial Research Group, School of Neurology, Neurobiology, and Psychiatry, The Medical School, The University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom
§ MitoKor Inc., San Diego, California

Address for correspondence and reprints: Dr. Neil Howell, MIGENIX Inc., Suite 210, 12780, High Bluff Drive, San Diego CA 92130, Email: NHowell{at}migenix.com, Telephone: 858/509-5616, FAX: 858/793-7805

Received for publication March 16, 2007. Revision received June 18, 2007. Accepted for publication July 16, 2007.

Reduced median networks of African haplogroup L mtDNA sequences were analyzed to determine the pattern of substitutions in both the non-coding control and coding regions. In particular, we attempted to determine the causes of the previously reported (Howell et al. 2004) violation of the molecular clock during the evolution of these sequences. In the coding region, there was a significantly higher rate of substitution at synonymous sites than at non-synonymous sites, as well as in the tRNA and rRNA genes. This is further evidence for the operation of purifying selection during human mtDNA evolution. For most sites in the control region, the relative rate of substitution was similar to the rate of neutral evolution (assumed to be most closely approximated by the substitution rate at 4-fold degenerate sites). However, there are a number of mutational hotspots in the control region, ~3% of the total sites, that have a rate of substitution greater than the neutral rate, at some sites by more than an order of magnitude. It is possible either that these sites are evolving under conditions of positive selection, or that the substitution rate at some sites in the control region is strongly dependent upon sequence context. Finally, we obtained preliminary evidence for "non-ideal" evolution in the control region, including haplogroup-specific substitution patterns and a decoupling between relative rates of substitution in the control and coding regions.

Key Words: mitochondrial DNA • molecular clock • phylogenetic analysis • selection • molecular evolution


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