Abstract
To analyze the distribution pattern of nucleotide substitutions in human mitochondrial DNA (mtDNA), mutational spectra of the mitochondrial genes were reconstructed. The reconstruction procedure is based on the mutation distribution data for 47 monophyletic mtDNA clusters, to which 794 examined mtDNA sequences encoding for tRNAs, rRNAs, and mitochondrial proteins are attributed. One of specific features of mitochondrial mutational spectra revealed was homoplasy of the mutations (the mean mutation number per variable nucleotide site in the coding region varied from 1.09 to 1.43). It was established that in the mtDNA genes maximum mutational constraint fell onto the guanine bases, albeit the content of these bases in the mtDNA L-chains was minimal. Maximal bias towards parallel G to A transitions was observed for rRNA genes, with the protein-and tRNA-encoding genes ranking next. Despite the fact that the differences in the average G-nucleotides content and variability between the genes of two mtDNA segments located between the OriH and OriL were statistically significant, the results did not provide the conclusion that the G-nucleotide instability observed in the mtDNA L-spectra was determined by the mechanism of asynchronous mtDNA replication, along with the deamination of cytosines in the H-chain regions, which remained single-stranded during replication.
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REFERENCES
Ingman, M., Kaessmann, H., Paabo, S., and Gyllensten, U., Mitochondrial Genome Variation and the Origin of Modern Humans, Nature, 2000, vol. 408, pp. 708–713.
Maca-Meyer, N., Gonzalez, A.M., Larruga, J.M., et al., Major Genomic Mitochondrial Lineages Delineate Early Human Expansions, BMC Genet., 2001, vol. 2, p. 13.
Finnila, S., Lehtonen, M.S., and Majamaa, K., Phylogenetic Network for European mtDNA, Am. J. Hum. Genet., 2001, vol. 68, pp. 1475–1484.
Herrnstadt, C., Elson, J.L., Fahy, E., et al., Reduced-Median-Network Analysis of Complete Mitochondrial DNA Coding-Region Sequences for the Major African, Asian and European Haplogroups, Am. J. Hum. Genet., 2002, vol. 70, pp. 1152–1171.
Hedges, S.B., A Start for Population Genomics, Nature, 2000, vol. 408, pp. 652–653.
Anderson, S., Bankier, A.T., Barrel, B.G., et al., Sequence and Organization of the Human Mitochondrial Genome, Nature, 1981, vol. 290, pp. 457–465.
Mishmar, D., Ruiz-Pesini, E., Golik, P., et al., Natural Selection Shaped Regional mtDNA Variation in Humans, Proc. Natl. Acad. Sci. USA, 2003, vol. 100, pp. 171–176.
Moilanen, J.S. and Majamaa, K., Phylogenetic Network and Physicochemical Properties of Nonsynonymous Mutations in the Protein-Coding Genes of Human Mitochondrial DNA, Mol. Biol. Evol., 2003, vol. 20, pp. 1195–1210.
Meyer, S. and von Haeseler, A., Identifying Site-Specific Substitution Rates, Mol. Biol. Evol., 2003, vol. 20, pp. 182–189.
Andrews, R.M., Kubacka, I., Chinnery, P.F., et al., Reanalysis and Revision of the Cambridge Reference Sequence for Human Mitochondrial DNA, Nat. Genet., 1999, vol. 23, p. 147.
Kumar, S., Tamura, K., Jakobsen, I.B., and Nei, M., MEGA2: Molecular Evolutionary Genetics Analysis Software, Arizona State Univ. Press, 2000.
Macaulay, V., Richards, M., Hickey, E., et al., The Emerging Tree of West Eurasian mtDNAs: A Synthesis of Control-Region Sequences and RFLPs, Am. J. Hum. Genet., 1999, vol. 64, pp. 232–249.
Sueoka, N., Intrastrand Parity Rules of DNA Base Composition and Usage Biases of Synonymous Codons, J. Mol. Evol., 1995, vol. 40, pp. 318–325.
Malyarchuk, B.A., Rogozin, I.B., Berikov, V.B., and Derenko, M.V., Analysis of Phylogenetically Reconstructed Mutational Spectra in Human Mitochondrial DNA Control Region, Hum. Genet., 2002, vol. 111, pp. 46–53.
Majewski, J., Dependence of Mutational Asymmetry on Gene-Expression Levels in the Human Genome, Am. J. Hum. Genet., 2003, vol. 73, pp. 688–692.
Tanaka, M. and Ozawa, T., Strand Asymmetry in Human Mitochondrial DNA Mutations, Genomics, 1994, vol. 22, pp. 327–335.
Green, P., Ewing, B., Miller, W., et al., Transcription-Associated Mutational Asymmetry in Mammalian Evolution, Nat. Genet., 2003, vol. 33, pp. 514–517.
Clayton, D.A., Replication and Transcription of Vertebrate Mitochondrial DNA, Annu. Rev. Cell Biol., 1991, vol. 7, pp. 453–478.
Reyes, A., Gissi, C., Pesole, G., and Saccone, C., Asymmetrical Directional Mutation Pressure in the Mitochondrial Genome of Mammals, Mol. Biol. Evol., 1998, vol. 15, pp. 957–966.
Tamura, K., On the Estimation of the Rate of Nucleotide Substitution for the Control Region of Human Mitochondrial DNA, Gene, 2000, vol. 259, pp. 189–197.
Beletskii, A. and Bhagwat, A.S., Transcription-Induced Mutations: Increase in C to T Mutations in the Nontranscribed Strand during Transcription in Escherichia coli, Proc. Natl. Acad. Sci. USA, 1996, vol. 93, pp. 13 919–13 924.
Malyarchuk, B.A., The Effect of the Nucleotide Context on Induction of Mutations in Hypervariable Segment 1 of Human Mitochondrial DNA, Mol. Biol. (Moscow), 2002, vol. 36, no. 3, pp. 418–423.
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Translated from Genetika, Vol. 41, No. 1, 2005, pp. 93–99.
Original Russian Text Copyright © 2005 by Malyarchuk.
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Malyarchuk, B.A. Distribution of nucleotide substitutions in human mitochondrial DNA genes. Russ J Genet 41, 79–84 (2005). https://doi.org/10.1007/s11177-005-0073-1
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DOI: https://doi.org/10.1007/s11177-005-0073-1