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Investigation of Heteroplasmy in the Human Mitochondrial DNA Control Region: A Synthesis of Observations from More Than 5000 Global Population Samples

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Abstract

Instances of point and length heteroplasmy in the mitochondrial DNA control region were compiled and analyzed from over 5,000 global human population samples. These data represent observations from a large and broad population sample, representing nearly 20 global populations. As expected, length heteroplasmy was frequently observed in the HVI, HVII and HVIII C-stretches. Length heteroplasmy was also observed in the AC dinucleotide repeat region, as well as other locations. Point heteroplasmy was detected in approximately 6% of all samples, and while the vast majority of heteroplasmic samples comprised two molecules differing at a single position, samples exhibiting two and three mixed positions were also observed in this data set. In general, the sites at which heteroplasmy was most commonly observed correlated with reported control region mutational hotspots. However, for some sites, observations of heteroplasmy did not mirror established mutation rate data, suggesting the action of other mechanisms, both selective and neutral. Interestingly, these data indicate that the frequency of heteroplasmy differs between particular populations, perhaps reflecting variable mutation rates among different mtDNA lineages and/or artifacts of particular population groups. The results presented here contribute to our general understanding of mitochondrial DNA control region heteroplasmy and provide additional empirical information on the mechanisms contributing to mtDNA control region mutation and evolution.

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Acknowledgments

The authors thank Heather Williams, Jennifer O’Callaghan, Carla Paintner, Jennifer Bas, Kimberly Watson, Daniela Niederwieser, Bettina Zimmermann, and Gabriela Huber for excellent technical assistance; Rebecca Just and Michael Coble for helpful discussion; and the American Registry of Pathology, James Canik, Brion Smith, and Louis Finelli for logistical and administrative support. We also thank the numerous collaborators who have kindly contributed population samples. Portions of this work were supported by a National Institute of Justice grant to T. J. P (Grant No. 2000-1 J-CX-K010) by the FWF Austrian Science Fund (TR397). The opinions and assertions contained herein are solely those of the authors and are not to be construed as official or as views of the United States Department of Defense, the United States Department of the Army, or the United States Department of Justice.

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Authors and Affiliations

  1. Research Department, Armed Forces DNA Identification Laboratory, 1413 Research Blvd., Rockville, MD, 20850, USA

    Jodi A. Irwin, Jessica L. Saunier, Kimberly A. Sturk & Toni M. Diegoli

  2. Institute of Legal Medicine, Innsbruck Medical University, Innsbruck, Austria

    Harald Niederstätter & Walther Parson

  3. Seattle Biomedical Research Institute, 307 Westlake Avenue North, Seattle, WA, 98109, USA

    Katharine M. Strouss

  4. Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria

    Anita Brandstätter

  5. International Commission on Missing Persons, Alipašina 45 A, 71000, Sarajevo, Bosnia and Herzegovina

    Thomas J. Parsons

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  1. Jodi A. Irwin
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Correspondence to Jodi A. Irwin.

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239_2009_9227_MOESM1_ESM.doc

Supplementary Table S1 is available online. Haplotype data are available on request. Sequences from this data set may also be found at www.empop.org or under the following GenBank accession numbers: DQ906346-DQ906708; FJ026015-FJ026391; DQ418040-DQ418130; EU718790-EU719066; DQ418131-DQ418449; EU014897-EU015024; DQ359273-DQ359688; AY632902-AY633004; and DQ535903-DQ536089. 1 (DOC 436 kb)

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Irwin, J.A., Saunier, J.L., Niederstätter, H. et al. Investigation of Heteroplasmy in the Human Mitochondrial DNA Control Region: A Synthesis of Observations from More Than 5000 Global Population Samples. J Mol Evol 68, 516–527 (2009). https://doi.org/10.1007/s00239-009-9227-4

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