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.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
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
Avise JC, Neigel JE, Arnold J (1984) Demographic influences on mitochondrial DNA lineage survivorship in animal populations. J Mol Evol 20:99–105
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
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
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
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
Brown W (1980) Polymorphism in mitochondrial DNA of humans as revealed by restriction endonuclease analysis. Proc Natl Acad Sci USA 77:3605–3609
Brown W, George M, Wilson AC (1979) Rapid evolution of animal mitochondrial DNA. Proc Natl Acad Sci USA 76:1967–1971
Cann RL, Stoneking M, Wilson AC (1987) Mitochondrial DNA and human evolution. Nature 325:31–36
Chakraborty R (1990) Mitochondrial DNA polymorphism reveals hidden heterogeneity within some Asian populations. Am J Hum Genet 47:87–94
Clark AG (1987) Neutrality tests of highly polymorphic RFLPs. Am J Hum Genet 41:948–956
De Benedictis G, Rose G, Caccio S, Picardi P, Quagliariello C (1989a) Mitochondrial DNA polymorphism in Calabria (southern Italy). Gene Geography 3:33–40
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
Di Rienzo A, Wilson AC (1991) Branching pattern in the evolutionary tree for human mitochondrial DNA. Proc Natl Acad Sci USA 88:1597–1601
Engels WR (1981) Estimating genetic divergence and genetic variability with restriction endonucleases. Proc Natl Acad Sci USA 78:6329–6333
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
Excoffier L, Langaney A (1989) Origin and differentiation of human mitochondrial DNA. Am J Hum Genet 44:73–85
Ewens WJ (1972) The sampling theory of selectively neutral alleles. Theor Pop Biol 3:87–112
Harihara S, Hirai M, Omoto K (1986) Mitochondrial DNA polymorphism in Japanese living in Hokkaido. Jpn J Hum Genet 31:73–83
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
Hasegawa M, Horai S (1991) Time of the deepest root for polymorphism in human mitochondrial DNA. J Mol Evol 32:37–42
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
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
Horai S, Gojobori T, Matsunaga E (1986) Distinct clustering of mitochondrial DNA types among Japanese, Caucasians, and Negroes. Jpn J Genet 61:271–275
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
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
Krüger, J, Vogel L (1989) The problem of our common mitochondrial mother. Hum Genet 82:308–312
Lewontin RC (1988) On measures of gametic disequilibrium. Genetics 120:849–852
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
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
Nei M, Li W-H (1975) The transient distribution of allele frequencies under mutation pressure Genet Res 28:205–214
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
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
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
Nei M, Tajima F (1983) Maximum likelihood estimation of the number of nucleotide substitutions from restriction site data. Genetics 105:207–217
Nei M, Maruyama T, Chakraborty R (1975) The bottleneck effect and genetic variability in populations. Evolution 29:1–10
Saitou N, Nei M (1987) The neighbor-joining method: a new method for constructing phylogenetic trees. Mol Biol Evol 4:406–425
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
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
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
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
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
Shutler R (ed) (1983) Early man in the New World. Sage Publications, Beverly Hills, CA
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
Stewart FM (1977) Computer algorithm for obtaining a random set of allele frequencies for a locus in an equilibrium population. Genetics 86:482–483
Stoneking M (1990) Departure of human mitochondrial DNA variation from neutral expectations: an alternative explanation. J Mol Evol 31:343–346
Stoneking M, Jorde LB, Bhatia K, Wilson AC (1990) Geographic variation in human mitochondrial DNA from Papua New Guinea. Genetics 124:717–733
Tajima F (1983) Evolutionary relationship of DNA sequences in finite populations. Genetics 105:437–460
Tajima F (1989a) Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123:585–595
Tajima F (1989b) The effect of change in population size on DNA polymorphism. Genetics 123:597–601
Takahata N, Palumbi SR (1985) Extranulcear differentiation and gene flow in the finite island model. Genetics 109:441–457
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
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
Vilkki J, Savontaus M, Nikoskelainen EK (1988) Human mitochondrial DNA in Finland. Hum Genet 80:317–321
Wallace DC, Garrison K, Knowler WC (1985) Dramatic founder effects in Amerindian mitochondrial DNAs. Am J Phys Anthropol 68:149–155
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
Watterson GA (1977) The homozygosity test of neutrality. Genetics 88:405–417
Weir BS (1990) Genetic data analysis. Sinauer, Sunderland MA
Weir BS, Cockerham CC (1984) EstimatingF-statistics for the analysis of population structure. Evolution 38:1358–1370
Weiss KM (1989) On the number of members of the genusHomo who have ever lived, and some evolutionary implications. Hum Biol 56:637–650
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
Author information
Authors and Affiliations
Rights 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
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02102807