Skip to main content
SpringerLink
Log in

The structure of human mitochondrial DNA variation

  • Published:
Journal of Molecular Evolution Aims and scope Submit manuscript

Summary

Restriction analysis of mitochondrial DNA (mtDNA) of 3065 humans from 62 geographic samples identified 149 haplotypes and 81 polymorphic sites. These data were used to test several aspects of the evolutionary past of the human species. A dendrogram depicting the genetic relatedness of all haplotypes shows that the native African populations have the greatest diversity and, consistent with evidence from a variety of sources, suggests an African origin for our species. The data also indicate that two individuals drawn, at random from the entire sample will differ at approximately 0.4% of their mtDNA nucleotide sites, which is somewhat higher than previous estimates. Human mtDNA also exhibits more interpopulation heterogeneity (GST=0.351±0.025) than does nuclear DNA (GST=0.12). Moreover, the virtual absence of intermediate levels of linkage disequilibrium between pairs of sites is consistent with the absence of genetic recombination and places constraints on the rate of mutation. Tests of the selective neutrality of mtDNA variation, including the Ewens-Watterson and Tajima tests, indicate a departure in the direction consistent with purifying selection, but this departure is more likely due to the rapid growth of the human population and the geographic heterogeneity of the variation. The lack of a good fit to neutrality poses problems for the estimation of times of coalescence from human mtDNA data.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Anderson S, Bankier AT, Barrel BG, DeBrulin MHL, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, Schreier PH, Smith AJH, Staden R, Young IG (1981) Sequence and organization of the human mitochondrial genome. Nature 290:457–465

    PubMed  Google Scholar 

  • Avise JC, Neigel JE, Arnold J (1984) Demographic influences on mitochondrial DNA lineage survivorship in animal populations. J Mol Evol 20:99–105

    PubMed  Google Scholar 

  • Avise JC, Ball RM, Arnold J (1988) Current versus historical population sizes in vertebrate species with high gene flow: a comparison based on mitochondrial DNA lineages and inbreeding theory for neutral mutations. Mol Biol Evol 5:331–344

    Google Scholar 

  • Ballinger SW, Schurr TG, Torroni A, Gan YY, Hodge J, Hassan K, Chen KH, Wallace DC (1991) Southeast Asian mitochondrial DNA analysis reveals genetic continuity of ancient mongoloid migrations. Genetics (in press)

  • Bonné-Tamir B, Johnson MJ, Natali A, Wallace DC, Cavalli-Sforza LL (1986) Human mitochondrial DNA types in two Israeli populations — a comparative study at the DNA level. Am J Hum Genet 38:341–351

    PubMed  Google Scholar 

  • Brega A, Scozzari R, Maccioni L, Iodice C, Wallace DC, Bianco I, Cao A, Santachiara Benerecetti AS (1986a) Mitochondrial DNA polymorphisms in Italy I. Population data from Sardinia and Rome. Ann Hum Genet 50:327–338

    PubMed  Google Scholar 

  • Brega A, Gardella R, Semino O, Morpurgo G, Astaldi Ricotti GB, Wallace DC, Santachiara Benerecetti AS (1986b) Genetic studies of the Tharu populations of Nepal: restriction endonuclease polymorphisms of mitochondrial DNA. Am J Hum Genet 39:502–512

    PubMed  Google Scholar 

  • Brown W (1980) Polymorphism in mitochondrial DNA of humans as revealed by restriction endonuclease analysis. Proc Natl Acad Sci USA 77:3605–3609

    PubMed  Google Scholar 

  • Brown W, George M, Wilson AC (1979) Rapid evolution of animal mitochondrial DNA. Proc Natl Acad Sci USA 76:1967–1971

    PubMed  Google Scholar 

  • Cann RL, Stoneking M, Wilson AC (1987) Mitochondrial DNA and human evolution. Nature 325:31–36

    PubMed  Google Scholar 

  • Chakraborty R (1990) Mitochondrial DNA polymorphism reveals hidden heterogeneity within some Asian populations. Am J Hum Genet 47:87–94

    PubMed  Google Scholar 

  • Clark AG (1987) Neutrality tests of highly polymorphic RFLPs. Am J Hum Genet 41:948–956

    PubMed  Google Scholar 

  • De Benedictis G, Rose G, Caccio S, Picardi P, Quagliariello C (1989a) Mitochondrial DNA polymorphism in Calabria (southern Italy). Gene Geography 3:33–40

    PubMed  Google Scholar 

  • De Benedictis G, Rose G, Passarino G, Quagliariello C (1989b) Restriction fragment length polymorphism of human mitochondrial DNA in a sample population from Apulia (southern Italy). Ann Hum Genet 53:311–318

    PubMed  Google Scholar 

  • Di Rienzo A, Wilson AC (1991) Branching pattern in the evolutionary tree for human mitochondrial DNA. Proc Natl Acad Sci USA 88:1597–1601

    PubMed  Google Scholar 

  • Engels WR (1981) Estimating genetic divergence and genetic variability with restriction endonucleases. Proc Natl Acad Sci USA 78:6329–6333

    PubMed  Google Scholar 

  • Excoffier L (1990) Evolution of human mitochondrial DNA: evidence for departure from a pure neutral model of populations at equilibrium. J Mol Evol 30:125–139

    PubMed  Google Scholar 

  • Excoffier L, Langaney A (1989) Origin and differentiation of human mitochondrial DNA. Am J Hum Genet 44:73–85

    PubMed  Google Scholar 

  • Ewens WJ (1972) The sampling theory of selectively neutral alleles. Theor Pop Biol 3:87–112

    Google Scholar 

  • Harihara S, Hirai M, Omoto K (1986) Mitochondrial DNA polymorphism in Japanese living in Hokkaido. Jpn J Hum Genet 31:73–83

    Google Scholar 

  • Harihara S, Saitou N, Hirai M, Gojobori T, Park KS, Misawa S, Ellepola SB, Ishida T, Omoto K (1988) Mitochondrial DNA polymorphisms among five Asian populations. Am J Hum Genet 43:134–143

    PubMed  Google Scholar 

  • Hasegawa M, Horai S (1991) Time of the deepest root for polymorphism in human mitochondrial DNA. J Mol Evol 32:37–42

    PubMed  Google Scholar 

  • Horai S, Hayasaka K (1990) Intraspecific nucleotide sequence differences in the major noncoding region of human mitochondrial DNA. Am J Hum Genet 46:828–842

    PubMed  Google Scholar 

  • Horai S, Matsunaga E (1986) Mitochondrial DNA polymorphism in Japanese. II. Analysis with restriction enzymes of four or five base pair recognition. Hum Genet 72:105–117

    PubMed  Google Scholar 

  • Horai S, Gojobori T, Matsunaga E (1986) Distinct clustering of mitochondrial DNA types among Japanese, Caucasians, and Negroes. Jpn J Genet 61:271–275

    Google Scholar 

  • Johanson D, Taieb M, Coppens, Y (1982) Pliocene hominoids from the Hadar Formation, Ethiopia (1973–1977): stratigraphic, chronologic, and paleoenvironmental contexts, with notes on hominoid morphology and systematics. Am J Phys Anthropol 57:373–402

    PubMed  Google Scholar 

  • Johnson MJ, Wallace DC, Ferris SD, Rattazzi MC, Cavalli-Svorza LL (1983) Radiation of human mitochondria DNA types analyzed by restriction endonuclease cleavage patterns. J Mol Evol 19:255–271

    PubMed  Google Scholar 

  • Krüger, J, Vogel L (1989) The problem of our common mitochondrial mother. Hum Genet 82:308–312

    PubMed  Google Scholar 

  • Lewontin RC (1988) On measures of gametic disequilibrium. Genetics 120:849–852

    PubMed  Google Scholar 

  • Li W-H, Sadler LA (1991) Low nucleotide diversity in man. Genetics (in press).

  • Livshits G, Nei M (1990) Relationships between intrapopulational and interpopulational genetic diversity in man. Ann Hum Biol, 17:501–513

    PubMed  Google Scholar 

  • Miyata T, Hayashida H, Kikuno R, Hasegawa M, Koyabashi M, Koike K (1982) Molecular clock of silent substitutions: at least a six-fold preponderance of silent changes in mitochondrial genes over those in nuclear genes. J Mol Evol 19:28–35

    PubMed  Google Scholar 

  • Nei M, Li W-H (1975) The transient distribution of allele frequencies under mutation pressure Genet Res 28:205–214

    Google Scholar 

  • Nei M, Li W-H (1979) Mathematical model for studying genetic variation in terms of restriction endonucleases. Proc Natl Acad Sci USA 76:5269–5273

    PubMed  Google Scholar 

  • Nei M, Livshits G (1990) Evolutionary relationships of Europeans, Asians, and Africans at the molecular level. In: Takahata, N, Crow J (eds) Population biology of genes and molecules. Baifukan, Tokyo, pp 251–266

    Google Scholar 

  • Nei M, Miller JC (1990) A simple method for estimating average number of nucleotide substitutions within and between populations from restriction data. Genetics 125:873–879

    PubMed  Google Scholar 

  • Nei M, Tajima F (1983) Maximum likelihood estimation of the number of nucleotide substitutions from restriction site data. Genetics 105:207–217

    PubMed  Google Scholar 

  • Nei M, Maruyama T, Chakraborty R (1975) The bottleneck effect and genetic variability in populations. Evolution 29:1–10

    Google Scholar 

  • Saitou N, Nei M (1987) The neighbor-joining method: a new method for constructing phylogenetic trees. Mol Biol Evol 4:406–425

    PubMed  Google Scholar 

  • Santachiara Benerecetti AS, Scozzari R, Semino O, Torroni A, Brega A, Wallace DC (1988) Mitochondrial DNA polymorphisms in Italy. II. Molecular analysis of new and rare morphs from Sardinia and Rome. Ann Hum Genet 52:39–56

    PubMed  Google Scholar 

  • Sartoris S, Varetto O, Migone N, Cappello N, Piazza A, Ferrara GB, Ceppellini R (1988) Mitochondrial DNA polymorphism in four Sardinian villages. Ann Hum Genet 52:327–340

    PubMed  Google Scholar 

  • Schurr TG, Ballinger SW, Gan YY, Hodge JA, Merriwether DA, Lawrence DN, Knowler WC, Weiss KM, Wallace DC (1990) Amerindian mitochondrial DNAs have rare Asian mutations at high frequencies suggesting a limited number of founders. Am J Hum Genet 46:613–623

    PubMed  Google Scholar 

  • Scozzari R, Torroni A, Semino O, Sirugo G, Brega A, Santachiara Benerecetti AS (1988) Genetic studies on the Senegal population I. Mitochondrial DNA polymorphisms. Am J Hum Genet 43:534–544

    PubMed  Google Scholar 

  • Semino O, Torroni A, Scozzari R, Brega A, DeBenedictis G, Santachiara Benerecetti AS (1989) Mitochondrial DNA polymorphisms in Italy. III. Population data from Sicily: a possible quantitation of maternal African ancestry. Ann Hum Genet 53:193–202

    PubMed  Google Scholar 

  • Shutler R (ed) (1983) Early man in the New World. Sage Publications, Beverly Hills, CA

    Google Scholar 

  • Slatkin M, Hudson RR (1991) Pairwise comparisons of mitochondrial DNA sequences in stable and exponentially growing populations. Genetics (in press)

  • Spuhler JN (1988) Evolution of mitochondrial DNA in monkeys, apes, and humans. Year Book Phys Anthropol 31:15–48

    Google Scholar 

  • Stewart FM (1977) Computer algorithm for obtaining a random set of allele frequencies for a locus in an equilibrium population. Genetics 86:482–483

    Google Scholar 

  • Stoneking M (1990) Departure of human mitochondrial DNA variation from neutral expectations: an alternative explanation. J Mol Evol 31:343–346

    PubMed  Google Scholar 

  • Stoneking M, Jorde LB, Bhatia K, Wilson AC (1990) Geographic variation in human mitochondrial DNA from Papua New Guinea. Genetics 124:717–733

    PubMed  Google Scholar 

  • Tajima F (1983) Evolutionary relationship of DNA sequences in finite populations. Genetics 105:437–460

    PubMed  Google Scholar 

  • Tajima F (1989a) Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123:585–595

    PubMed  Google Scholar 

  • Tajima F (1989b) The effect of change in population size on DNA polymorphism. Genetics 123:597–601

    PubMed  Google Scholar 

  • Takahata N, Palumbi SR (1985) Extranulcear differentiation and gene flow in the finite island model. Genetics 109:441–457

    Google Scholar 

  • Torroni A, Semino O, Rose G, De Benedictis G, Brancati C, Santachiara Benerecetti AS (1990) Mitochondrial DNA polymorphisms in the Albanian population of Calabria (southern Italy). Int J Anthropol 5:97–104

    Google Scholar 

  • Torroni A, Schurr TG, Yang CC, Szathmary EJE, Williams RC, Schanfield MS, Troup GA, Knowlder WC, Lawrence DN, Weiss KM, Wallace DC (1991) Amerindian mitochondrial DNA analysis reveals pre-Clovis colonization of the New World. Genetics (in press)

  • Vigilant L, Pennington R, Harpending H, Kocher TD, Wilson AC (1989) Mitochondrial DNA sequences in single hairs from a southern African population. Proc Natl Acad Sci USA 86:9350–9354

    PubMed  Google Scholar 

  • Vilkki J, Savontaus M, Nikoskelainen EK (1988) Human mitochondrial DNA in Finland. Hum Genet 80:317–321

    PubMed  Google Scholar 

  • Wallace DC, Garrison K, Knowler WC (1985) Dramatic founder effects in Amerindian mitochondrial DNAs. Am J Phys Anthropol 68:149–155

    PubMed  Google Scholar 

  • Wallace DC, Singh G, Lott MT, Hodge JA, Schurr TG, Lezza AMS, Elsas LJ, Nikoskelainen EK (1988) Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. Science 242:1427–1430

    PubMed  Google Scholar 

  • Watterson GA (1977) The homozygosity test of neutrality. Genetics 88:405–417

    Google Scholar 

  • Weir BS (1990) Genetic data analysis. Sinauer, Sunderland MA

    Google Scholar 

  • Weir BS, Cockerham CC (1984) EstimatingF-statistics for the analysis of population structure. Evolution 38:1358–1370

    Google Scholar 

  • Weiss KM (1989) On the number of members of the genusHomo who have ever lived, and some evolutionary implications. Hum Biol 56:637–650

    Google Scholar 

  • Whittam TS, Clark AG, Stoneking M, Cann RL, Wilson AC (1986) Allelic variation in human mitochondrial genes based on patterns of restriction site polymorphism. Proc Natl Acad Sci USA 83:9611–9615

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Human Genetics, School of Public Health, University of Pittsburgh, 15261, Pittsburgh, PA, USA

    D. Andrew Merriwether

  2. Department of Biology and Institute of Molecular Evolutionary Genetics, Pennsylvania State University, 16802, University Park, PA, USA

    Andrew G. Clark

  3. Center for Genetics and Molecular Medicine, Emory University School of Medicine, Rollins Research Center, 30322, Atlanta, GA, USA

    Scott W. Ballinger, Theodore G. Schurr & Douglas C. Wallace

  4. MRC Human Ecogenetics Research Unit, Department of Human Genetics, School of Pathology, South African Institute for Medical Research, Johannesburg, South Africa

    Himla Soodyall & Trefor Jenkins

  5. the University of the Witwatersrand, Johannesburg, South Africa

    Himla Soodyall & Trefor Jenkins

  6. Department of Anthropology, Pennsylvania State University, 16802, University Park, PA, USA

    Stephen T. Sherry

Authors
  1. D. Andrew Merriwether
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrew G. Clark
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Scott W. Ballinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Theodore G. Schurr
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Himla Soodyall
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Trefor Jenkins
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Stephen T. Sherry
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Douglas C. Wallace
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Merriwether, D.A., Clark, A.G., Ballinger, S.W. et al. The structure of human mitochondrial DNA variation. J Mol Evol 33, 543–555 (1991). https://doi.org/10.1007/BF02102807

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02102807

Key words

Search

Navigation