Abstract
Four nuclear pseudogenes homologous to the 10031–10195-bp region of the human mitochondrial genome were detected by constant denaturant capillary electrophoresis. Among them, one pseudogene is present as at least five copies in each cell, in accordance with our previous observations of multi-copy mitochondrial DNA pseudogenes. The presence of multiple identical copies of pseudogenes suggests that the human genome underwent a series of genetic changes, including gene amplifications, very recently in evolutionary history, i.e., within the last 390000 years.
Similar content being viewed by others
References
Anderson SA, Bankier AT, Barrell BG, de Bruijn MHL, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, Schreir PH, Smith AJH, Staden R, Young IG (1981) Sequence and organization of the human mitochondrial genome. Nature 290:457–465
Brown WM (1980) Polymorphism in mitochondrial DNA of humans as revealed by restriction endonuclease analysis. Proc Natl Acad Sci USA 77:3605–3609
Cann RL, Stongking M, Wilson AC (1987) Mitochondrial DNA and human evolution. Nature 325:31–36
Corral M, Baffet G, Kitzis A, Paris B, Tichonicky L, Kruh J, Guguen-Guillouzo C, Defer N (1989) DNA sequences homologous to mitochondrial genes in nuclei from normal rat tissues and from rat hepatoma cells. Biochem Biophys Res Comm 162:258–264
Cottrez F, Auriault C, Capron A, Groux H (1994) Quantitative PCR: validation of the use of a multispecific internal control. Nucleic Acids Res 22:2712–2713
Farrelly F, Butow RA (1983) Rearranged mitochondrial genes in the yeast nuclear genome. Nature 301:296–301
Fukuda M, Wakasugi S, Tsuzuki T, Nomiyama H, Shimada K, Miyata T (1985) Mitchondrial DNA-like sequences in the human nuclear genome: characterization and implications in the evolution of mitochondrial DNA. J Mol Biol 186:257–266
Gellissen G, Michaelis G (1987) Gene transfer, mitochondria to nucleus. Ann N Y Acad Sci 503:391–401
Gellissen G, Bradfield JY, White BN, Wyatt GR (1983) Mitochondrial DNA sequences in the nuclear genome of a locust. Nature 301:631–634
Gillespie JH (1986) Variability of evolutionary rates of DNA. Genetics 113:1077–1091
Hadler HI, Dimitrijevic B, Mahalingam R (1983) Mitochondrial DNA and nuclear DNA from normal rat liver have a common sequence. Proc Natl Acad Sci USA 80:6495–6499
Hayasaka K, Gojobori T, Horai S (1988) Molecular phylogeny and evolution of primate mitochondrial DNA. Mol Biol Evol 5:626–644
Heuvel JPV, Clark GC, Kohn MC, Tritscher AM, Greenlee WF, Lucier GW, Bell DA (1994) Dioxin-responsive Genes: examination of dose-response relationships using quantitative reverse transcriptase-polymerase chain reaction. Cancer Res 54:62–68
Hovius R, Lambrechts H, Nicolay K, Kruijff BD (1990) Improved methods to isolate and subfractionate rat liver mitochondria. Lipid composition of the inner and outer membrane. Biochim Biophy Acta 1021:217–226
Hu G (1993) DNA polymerase-catalyzed addition of nontemplated extra nucleotides to the 3′ end of a DNA fragment. DNA Cell Biol 12:763–770
Hu G, Thilly WG (1994) Evolutionary trail of mitochondrial genome as based on its pseudogenes for human 16s rDNA. Gene 147:197–204
Jacobs HT, Grimes B (1986) Complete nucleotide sequences of the nuclear pseudogenes for cytochrome oxidase subunit I and the large mitochondrial ribosomal RNA in the sea urchin Strongylocentrotus purpuratus. J Mio Biol 187:509–527
Jacobs HT, Posakony JW, Grula JW, Roberts JW, Xin J-H, Britten RJ, Davidson EH (1983) Mitochondrial DNA sequences in the nuclear genome of Strongylocentrotus purpuratus. J Mol Biol 165:609–632
Jones JS, Rouhani S (1986) How small was the bottleneck? Nature 319:449–450
Kamimura N, Ishii S, Liandong M, Shay JW (1989) Three separate mitochondrial DNA sequences are contiguous in human genomic DNA. J Mol Biol 210:703–707
Keohaving P, Thilly WG (1989) Fidelity of DNA polymerizes in DNA amplification. Proc Natl Acad Sci USA 86:9253–9257
Khrapko K, Hanekamp JS, Thilly WG, Belenkii A, Foret F, Karger BL (1994) Constant denaturant capillary electrophoresis (CDCE): a high resolution approach to mutational analysis. Nucleic Acids Res 22:364–369
King MP, Attardi G (1989) Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation. Science 246:500–503
Kristensen T, Prydz H (1986) The presence of intact mitochondrial DNA in HeLa cell nuclei. Nucleic Acids Res 14:2597–2609
Lanave C, Preparata G, Saccone C (1985) Mammalian genes as molecular clocks. J Mol Evol 21:346–350
Li W-H, Luo C-C, Wu C-J (1985) Evolution of DNA sequences. In: MacIntyre RJ (ed) Molecular evolutionary genetics. Plenum, New York, pp 1–94
Morrison C, Gannon F (1994) The impact of PCR plateau phase on quantitative PCR. Biochim Biophys Acta 1219:493–498
Nomiyama H, Fukuda M, Wakasugi S, Tsuzuki T, Shimada K (1985) Molecular structures of mitochondrial-DNA-like sequences in human nuclear DNA. Nucleic Acids Res 13:1649–1658
Nomiyama H, Tsuzuki T, Wakasugi S, Fukuda M, Shimada K (1984) Interruption of a human nuclear sequence homologous to mitochondrial DNA by a member of the KpnI 1.8-kp family. Nucleic Acids Res 12:5225–5234
Petrenko AY, Sukach AN (1991) Isolation of intact mitochondria and hepatocytes using vibration. Analy Biochem 194:326–329
Rampino MR, Self S (1993) Bottleneck in human evolution and the Toba eruption. Science 262:1955
Schiestl RH, Dominska M, Petess TD (1993) Transformation of Saccharomyces cerevisiae with nonhomologous DNA: illegitimate ligation of transforming DNA into yeast chromosomes and in vivo ligation of transforming DNA to mitochondrial DNA sequences. Mol Cell Biol 13:2697–2705
Scott B, Bergseid M, Mathur S, Nielson K, Shoemaker D, Mathur E (1991) A high-fidelity thermostable DNA polymerase isolated from Pyrococcus furiosus. Strategies 4:34–35
Shoemaker JS, Fitch WM (1989) Evidence from nuclear sequences that invariable sites should be considered when sequences divergence is calculated. Mol Biol Evol 6:270–289
Stringer CB, Andrews P (1988) Genetic and fossil evidence for the origin of modern humans. Science 239:1263–1265
Tapper DP, Etten RAV, Clayton DA (1983) Isolation of mammalian mitochondrial DNA and RNA and cloning of the mitochondrial genome. Methods Enzymol 97:426–431
Thorsness PE, Fox TD (1990) Escape of DNA from mitochondria to the nucleus in Saccharomyces cerevisiae. Nature 346:376–379
Thorsness PE, Fox TD (1993) Nuclear mutations in Saccharomyces cerevisiae that affect the escape of DNA from mitochondria to the nucleus. Genetics 134:21–28
Timmis JN, Scott NS (1983) Sequence homology between spinach nuclear and chloroplast genomes. Nature 305:65–67
Tourmente S, Savre-Train I, Berthier F, Renaud M (1990) Expression of six mitochondrial genes during Drosophila oogenesis: analysis by in situ hybridization. Cell Diff Dev 31:137–149
Tsuzuki T, Nomiyama H, Setoyama C, Maeda S, Shimada K (1983) Presence of mitochondrial-DNA-like sequences in the human nuclear DNA. Gene 25:223–229
Van de Boogaart P, Samallo J, Agsteribbe E (1982) Similar genes for a mitochondrial ATPase subunit in the nuclear and mitochondrial genomes of Neurospora crassa. Nature 298:187–189
Vawter L, Brown WM (1986) Nuclear and mitochondrial DNA comparisons reveal extreme rate variation in the molecular clock. Science 234:194–196
Vigilant L, Pennington R, Harpending H, Kocher TD, Wilson AC (1989) Mitochondrial DNA sequences in single hair from a southern African population. Proc Natl Acad Sci USA 86:9350–9354
Vigilant L, Stoneking M, Harpending H, Hawkes K, Wilson AC (1991) African population and the evolution of human mitochondrial DNA. Science 253:1503–1507
Wakasugi S, Nomiyama H, Fukuda M, Tsuzuki T, Shimada K (1985) Insertion of a long KpnI family member within a mitochondrial-DNA-like sequence present in the human nuclear genome. Gene 36:281–288
Welter C, Dooley S, Blin N (1989) A rapid protocol for the purification of mitochondrial DNA suitable for studying restriction fragment length polymorphisms. Gene 83:167–172
Zullo S, Sieu LC, Slightom JL, Hadler HI, Eisenstad JM (1991) Mitochondrial D-loop sequences are integrated in the rat nuclear genome. J Mol Biol 221:1223–1235
Author information
Authors and Affiliations
Additional information
Communicated by R. J. Rothstein
Rights and permissions
About this article
Cite this article
Hu, G., Thilly, W.G. Multi-copy nuclear pseudogenes of mitochondrial DNA reveal recent acute genetic changes in the human genome. Curr Genet 28, 410–414 (1995). https://doi.org/10.1007/BF00310808
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00310808