Journal of Molecular Evolution

, Volume 68, Issue 5, pp 516-527

First online:

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

  • Jodi A. IrwinAffiliated withResearch Department, Armed Forces DNA Identification Laboratory Email author 
  • , Jessica L. SaunierAffiliated withResearch Department, Armed Forces DNA Identification Laboratory
  • , Harald NiederstätterAffiliated withInstitute of Legal Medicine, Innsbruck Medical University
  • , Katharine M. StroussAffiliated withSeattle Biomedical Research Institute
  • , Kimberly A. SturkAffiliated withResearch Department, Armed Forces DNA Identification Laboratory
  • , Toni M. DiegoliAffiliated withResearch Department, Armed Forces DNA Identification Laboratory
  • , Anita BrandstätterAffiliated withDivision of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University
  • , Walther ParsonAffiliated withInstitute of Legal Medicine, Innsbruck Medical University
  • , Thomas J. ParsonsAffiliated withInternational Commission on Missing Persons

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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.


Control region Heteroplasmy Mitochondrial DNA Mutation rate