Investigation of heteroplasmy in the human mitochondrial DNA control region: A synthesis of observations from more than 5000 global population samples

Jodi A. Irwin, Jessica L. Saunier, Harald Niederstätter, Katharine M. Strouss, Kimberly A. Sturk, Toni M. Diegoli, Anita Brandstätter, Walther Parson, Thomas John Parsons

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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.

Original languageEnglish (US)
Pages (from-to)516-527
Number of pages12
JournalJournal of Molecular Evolution
Volume68
Issue number5
DOIs
StatePublished - May 1 2009

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Mitochondrial DNA
mitochondrial DNA
mutation
synthesis
Mutation Rate
Population
Dinucleotide Repeats
sampling
artifact
Population Groups
Artifacts
human population
mechanism of action
Mutation
microsatellite repeats
rate

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics

Cite this

Irwin, Jodi A. ; Saunier, Jessica L. ; Niederstätter, Harald ; Strouss, Katharine M. ; Sturk, Kimberly A. ; Diegoli, Toni M. ; Brandstätter, Anita ; Parson, Walther ; Parsons, Thomas John. / Investigation of heteroplasmy in the human mitochondrial DNA control region : A synthesis of observations from more than 5000 global population samples. In: Journal of Molecular Evolution. 2009 ; Vol. 68, No. 5. pp. 516-527.
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Irwin, JA, Saunier, JL, Niederstätter, H, Strouss, KM, Sturk, KA, Diegoli, TM, Brandstätter, A, Parson, W & Parsons, TJ 2009, 'Investigation of heteroplasmy in the human mitochondrial DNA control region: A synthesis of observations from more than 5000 global population samples', Journal of Molecular Evolution, vol. 68, no. 5, pp. 516-527. https://doi.org/10.1007/s00239-009-9227-4

Investigation of heteroplasmy in the human mitochondrial DNA control region : A synthesis of observations from more than 5000 global population samples. / Irwin, Jodi A.; Saunier, Jessica L.; Niederstätter, Harald; Strouss, Katharine M.; Sturk, Kimberly A.; Diegoli, Toni M.; Brandstätter, Anita; Parson, Walther; Parsons, Thomas John.

In: Journal of Molecular Evolution, Vol. 68, No. 5, 01.05.2009, p. 516-527.

Research output: Contribution to journalArticle

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T1 - Investigation of heteroplasmy in the human mitochondrial DNA control region

T2 - A synthesis of observations from more than 5000 global population samples

AU - Irwin, Jodi A.

AU - Saunier, Jessica L.

AU - Niederstätter, Harald

AU - Strouss, Katharine M.

AU - Sturk, Kimberly A.

AU - Diegoli, Toni M.

AU - Brandstätter, Anita

AU - Parson, Walther

AU - Parsons, Thomas John

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N2 - 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.

AB - 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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