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A high observed substitution rate in the human mitochondrial DNA control region

Nature Genetics volume 15, pages 363–368 (1997)Cite this article

Abstract

The rate and pattern of sequence substitutions in the mitochondrial DNA (mtDNA) control region (CR) is of central importance to studies of human evolution and to forensic identity testing. Here, we report a direct measurement of the intergenerational substitution rate in the human CR. We compared DNA sequences of two CR hypervariable segments from close maternal relatives, from 134 independent mtDNA lineages spanning 327 generational events. Ten substitutions were observed, resulting in an empirical rate of 1/33 generations, or 2.5/site/Myr. This is roughly twenty-fold higher than estimates derived from phylogenetic analyses. This disparity cannot be accounted for simply by substitutions at mutational hot spots, suggesting additional factors that produce the discrepancy between very near-term and long-term apparent rates of sequence divergence. The data also indicate that extremely rapid segregation of CR sequence variants between generations is common in humans, with a very small mtDNA bottleneck. These results have implications for forensic applications and studies of human evolution.

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Author notes

  1. Thomas J. Parsons: Correspondence should be addressed to T.J.P.

Authors and Affiliations

  1. The Armed Forces DNA Identification Laboratory, Office of the Armed Forces Medical Examiner, The Armed Forces Institute of Pathology, 1413 Research Blvd, Rockville, Maryland, 20850, USA

    Thomas J. Parsons, David S. Muniec, Victor W. Weedn & Mitchell M. Holland

  2. The Forensic Science Service, Priory House, Gooch Street North, Birmingham, UK

    Kevin Sullivan, Nicola Woodyatt, Rosemary Alliston-Greiner & Peter Gill

  3. The FBI Laboratory, Washington, DC, 20535, USA

    Mark R. Wilson

  4. Department of Chemistry, Gettysburg College, Gettysburg, Pennsylvania, 17325, USA

    Dianna L. Berry & Koren A. Holland

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Parsons, T., Muniec, D., Sullivan, K. et al. A high observed substitution rate in the human mitochondrial DNA control region. Nat Genet 15, 363–368 (1997). https://doi.org/10.1038/ng0497-363

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