Mutagenesis by Transient Misalignment in the Human Mitochondrial DNA Control Region

Authors

  • B. A. Malyarchuk,

    Corresponding author
    1. Institute of Biological Problems of the North, Far-East Branch of the Russian Academy of Sciences, Portovaya str. 18, 68500 Magadan, Russia
      *Corresponding author: Dr. Boris A. Malyarchuk, Genetics Laboratory, Institute of Biological Problems of the North, Portovaya str., 18, 685000 Magadan, Russia. Fax/Phone: 7 41322 34463. E-mail: malyar@ibpn.kolyma.ru
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  • I. B. Rogozin

    1. Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia
    2. National Center for Biotechnology Information, NLM, National Institutes of Health, Bethesda MD 20894, USA
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*Corresponding author: Dr. Boris A. Malyarchuk, Genetics Laboratory, Institute of Biological Problems of the North, Portovaya str., 18, 685000 Magadan, Russia. Fax/Phone: 7 41322 34463. E-mail: malyar@ibpn.kolyma.ru

Summary

To study spontaneous base substitutions in human mitochondrial DNA (mtDNA), we reconstructed the mutation spectra of the hypervariable segments I and II (HVS I and II) using published data on polymorphisms from various human populations. Classification analysis revealed numerous mutation hotspots in HVS I and II mutation spectra. Statistical analysis suggested that strand dislocation mutagenesis, operating in monotonous runs of nucleotides, plays an important role in generating base substitutions in the mtDNA control region. The frequency of mutations compatible with the primer strand dislocation in the HVS I region was almost twice as high as that for template strand dislocation. Frequencies of mutations compatible with the primer and template strand dislocation models are almost equal in the HVS II region. Further analysis of strand dislocation models suggested that an excess of pyrimidine transitions in mutation spectra, reconstructed on the basis of the L-strand sequence, is caused by an excess of both L-strand pyrimidine transitions and H-strand purine transitions. In general, no significant bias toward parent H-strand-specific dislocation mutagenesis was found in the HVS I and II regions.

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