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Am J Hum Genet. Sep 1993; 53(3): 563–590.
PMCID: PMC1682412

Asian affinities and continental radiation of the four founding Native American mtDNAs.


The mtDNA variation of 321 individuals from 17 Native American populations was examined by high-resolution restriction endonuclease analysis. All mtDNAs were amplified from a variety of sources by using PCR. The mtDNA of a subset of 38 of these individuals was also analyzed by D-loop sequencing. The resulting data were combined with previous mtDNA data from five other Native American tribes, as well as with data from a variety of Asian populations, and were used to deduce the phylogenetic relationships between mtDNAs and to estimate sequence divergences. This analysis revealed the presence of four haplotype groups (haplogroups A, B, C, and D) in the Amerind, but only one haplogroup (A) in the Na-Dene, and confirmed the independent origins of the Amerinds and the Na-Dene. Further, each haplogroup appeared to have been founded by a single mtDNA haplotype, a result which is consistent with a hypothesized founder effect. Most of the variation within haplogroups was tribal specific, that is, it occurred as tribal private polymorphisms. These observations suggest that the process of tribalization began early in the history of the Amerinds, with relatively little intertribal genetic exchange occurring subsequently. The sequencing of 341 nucleotides in the mtDNA D-loop revealed that the D-loop sequence variation correlated strongly with the four haplogroups defined by restriction analysis, and it indicated that the D-loop variation, like the haplotype variation, arose predominantly after the migration of the ancestral Amerinds across the Bering land bridge.

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  • Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, et al. Sequence and organization of the human mitochondrial genome. Nature. 1981 Apr 9;290(5806):457–465. [PubMed]
  • Ballinger SW, Schurr TG, Torroni A, Gan YY, Hodge JA, Hassan K, Chen KH, Wallace DC. Southeast Asian mitochondrial DNA analysis reveals genetic continuity of ancient mongoloid migrations. Genetics. 1992 Jan;130(1):139–152. [PMC free article] [PubMed]
  • Barrantes R, Smouse PE, Mohrenweiser HW, Gershowitz H, Azofeifa J, Arias TD, Neel JV. Microevolution in lower Central America: genetic characterization of the Chibcha-speaking groups of Costa Rica and Panama, and a consensus taxonomy based on genetic and linguistic affinity. Am J Hum Genet. 1990 Jan;46(1):63–84. [PMC free article] [PubMed]
  • Brown MD, Voljavec AS, Lott MT, Torroni A, Yang CC, Wallace DC. Mitochondrial DNA complex I and III mutations associated with Leber's hereditary optic neuropathy. Genetics. 1992 Jan;130(1):163–173. [PMC free article] [PubMed]
  • Cann RL, Stoneking M, Wilson AC. Mitochondrial DNA and human evolution. Nature. 1987 Jan 1;325(6099):31–36. [PubMed]
  • Cann RL, Wilson AC. Length mutations in human mitochondrial DNA. Genetics. 1983 Aug;104(4):699–711. [PMC free article] [PubMed]
  • Chagnon NA, Neel JV, Weitkamp L, Gershowitz H, Ayres M. The influence of cultural factors on the demography and pattern of gene flow from the Makiritare to the Yanomama Indians. Am J Phys Anthropol. 1970 May;32(3):339–349. [PubMed]
  • Chakraborty R, Weiss KM. Genetic variation of the mitochondrial DNA genome in American Indians is at mutation-drift equilibrium. Am J Phys Anthropol. 1991 Dec;86(4):497–506. [PubMed]
  • Denaro M, Blanc H, Johnson MJ, Chen KH, Wilmsen E, Cavalli-Sforza LL, Wallace DC. Ethnic variation in Hpa 1 endonuclease cleavage patterns of human mitochondrial DNA. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5768–5772. [PMC free article] [PubMed]
  • Field LL, Gofton JP, Kinsella TD. Immunoglobulin (GM and KM) allotypes and relation to population history in native peoples of British Columbia: Haida and Bella Coola. Am J Phys Anthropol. 1988 Jun;76(2):155–163. [PubMed]
  • Gershowitz H, Layrisse M, Layrisse Z, Neel JV, Brewer C, Chagnon N, Ayres M. Gene frequencies and microdifferentiation among the Makiritare Indians. I. Eleven blood group systems and the ABH-Le secretor traits: a note on Rh gene frequency determinations. Am J Hum Genet. 1970 Sep;22(5):515–525. [PMC free article] [PubMed]
  • Giles RE, Blanc H, Cann HM, Wallace DC. Maternal inheritance of human mitochondrial DNA. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6715–6719. [PMC free article] [PubMed]
  • Gofton JP, Chalmers A, Price GE, Reeve CE. HL-A27 and ankylosing spondylitis in B.C. Indians. J Rheumatol. 1975 Sep;2(3):314–318. [PubMed]
  • Hedges SB, Kumar S, Tamura K, Stoneking M. Human origins and analysis of mitochondrial DNA sequences. Science. 1992 Feb 7;255(5045):737–739. [PubMed]
  • Hertzberg M, Mickleson KN, Serjeantson SW, Prior JF, Trent RJ. An Asian-specific 9-bp deletion of mitochondrial DNA is frequently found in Polynesians. Am J Hum Genet. 1989 Apr;44(4):504–510. [PMC free article] [PubMed]
  • Horai S, Matsunaga E. Mitochondrial DNA polymorphism in Japanese. II. Analysis with restriction enzymes of four or five base pair recognition. Hum Genet. 1986 Feb;72(2):105–117. [PubMed]
  • Johnson MJ, Wallace DC, Ferris SD, Rattazzi MC, Cavalli-Sforza LL. Radiation of human mitochondria DNA types analyzed by restriction endonuclease cleavage patterns. J Mol Evol. 1983;19(3-4):255–271. [PubMed]
  • Knowler WC, Bennett PH, Hamman RF, Miller M. Diabetes incidence and prevalence in Pima Indians: a 19-fold greater incidence than in Rochester, Minnesota. Am J Epidemiol. 1978 Dec;108(6):497–505. [PubMed]
  • Mohrenweiser H, Neel JV, Mestriner MA, Salzano FM, Migliazza E, Simões AL, Yoshihara CM. Electrophoretic variants in three Amerindian tribes: the Baniwa, Kanamari, and Central Pano of western Brazil. Am J Phys Anthropol. 1979 Feb;50(2):237–246. [PubMed]
  • Neel JV. Rare variants, private polymorphisms, and locus heterozygosity in Amerindian populations. Am J Hum Genet. 1978 Sep;30(5):465–490. [PMC free article] [PubMed]
  • Neel JV, Gershowitz H, Mohrenweiser HW, Amos B, Kostyu DD, Salzano FM, Mestriner MA, Lawrence D, Simões AL, Smouse PE, et al. Genetic studies on the Ticuna, an enigmatic tribe of Central Amazonas. Ann Hum Genet. 1980 Jul;44(Pt 1):37–54. [PubMed]
  • Neel JV, Gershowitz H, Spielman RS, Migliazza EC, Salzano FM, Oliver WJ. Genetic studies of the Macushi and Wapishana Indians. II. Data on 12 genetic polymorphisms of the red cell and serum proteins: gene flor between the tribes. Hum Genet. 1977 Jun 30;37(2):207–219. [PubMed]
  • Neel JV, Tanis RJ, Migliazza EC, Spielman RS, Salzano F, Oliver WJ, Morrow M, Bachofer S. Genetic studies of the Macushi and Wapishana Indians. I. Rare genetic variants and a "private polymorphism' of esterase A. Hum Genet. 1977 Apr 7;36(1):81–107. [PubMed]
  • Neel JV, Thompson EA. Founder effect and number of private polymorphisms observed in Amerindian tribes. Proc Natl Acad Sci U S A. 1978 Apr;75(4):1904–1908. [PMC free article] [PubMed]
  • Nei M, Tajima F. Maximum likelihood estimation of the number of nucleotide substitutions from restriction sites data. Genetics. 1983 Sep;105(1):207–217. [PMC free article] [PubMed]
  • Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT, Erlich HA, Arnheim N. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science. 1985 Dec 20;230(4732):1350–1354. [PubMed]
  • Salzano FM, Neel JV, Gershowitz H, Migliazza EC. Intra and intertribal genetic variation within a linguistic group: the Ge-speaking indians of Brazil. Am J Phys Anthropol. 1977 Sep;47(2):337–347. [PubMed]
  • Schell LM, Agarwal SS, Blumberg BS, Levy H, Bennett PH, Laughlin WS, Martin JP. Distribution of albumin variants Naskapi amd Mexico among Aleuts, Frobisher Bay Eskimos, and Micmac, Naskapi, Mohawk, Omaha, and Apache Indians. Am J Phys Anthropol. 1978 Jul;49(1):111–117. [PubMed]
  • Schurr TG, Ballinger SW, Gan YY, Hodge JA, Merriwether DA, Lawrence DN, Knowler WC, Weiss KM, Wallace DC. Amerindian mitochondrial DNAs have rare Asian mutations at high frequencies, suggesting they derived from four primary maternal lineages. Am J Hum Genet. 1990 Mar;46(3):613–623. [PMC free article] [PubMed]
  • Scozzari R, Torroni A, Semino O, Sirugo G, Brega A, Santachiara-Benerecetti AS. Genetic studies on the Senegal population. I. Mitochondrial DNA polymorphisms. Am J Hum Genet. 1988 Oct;43(4):534–544. [PMC free article] [PubMed]
  • Shields GF, Hecker K, Voevoda MI, Reed JK. Absence of the Asian-specific region V mitochondrial marker in Native Beringians. Am J Hum Genet. 1992 Apr;50(4):758–765. [PMC free article] [PubMed]
  • Shoffner JM, Lott MT, Lezza AM, Seibel P, Ballinger SW, Wallace DC. Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNA(Lys) mutation. Cell. 1990 Jun 15;61(6):931–937. [PubMed]
  • Stewart CB. The powers and pitfalls of parsimony. Nature. 1993 Feb 18;361(6413):603–607. [PubMed]
  • Stoneking M, Bhatia K, Wilson AC. Rate of sequence divergence estimated from restriction maps of mitochondrial DNAs from Papua New Guinea. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 1):433–439. [PubMed]
  • Stoneking M, Jorde LB, Bhatia K, Wilson AC. Geographic variation in human mitochondrial DNA from Papua New Guinea. Genetics. 1990 Mar;124(3):717–733. [PMC free article] [PubMed]
  • Szathmary EJ. Dogrib Indians of the Northwest Territories, Canada: genetic diversity and genetic relationship among subarctic Indians. Ann Hum Biol. 1983 Mar-Apr;10(2):147–162. [PubMed]
  • Szathmary EJ, Ritenbaugh C, Goodby CS. Dietary change and plasma glucose levels in an Amerindian population undergoing cultural transition. Soc Sci Med. 1987;24(10):791–804. [PubMed]
  • Szathmary EJ, Cox DW, Gershowitz H, Rucknagel DL, Schanfield MS. The Northern and Southeastern Ojibwa: serum proteins and red cell enzyme systems. Am J Phys Anthropol. 1974 Jan;40(1):49–65. [PubMed]
  • Tanis RJ, Neel JV, Dovey H, Morrow M. The genetic structure of a tribal population, the Yanomama Indians. IX. Gene frequencies for 18 serum protein and erythrocyte enzyme systems in the Yanomama and five neighboring tribes: nine new variants. Am J Hum Genet. 1973 Nov;25(6):655–676. [PMC free article] [PubMed]
  • Templeton AR. Human origins and analysis of mitochondrial DNA sequences. Science. 1992 Feb 7;255(5045):737–737. [PubMed]
  • Torroni A, Schurr TG, Yang CC, Szathmary EJ, Williams RC, Schanfield MS, Troup GA, Knowler WC, Lawrence DN, Weiss KM, et al. Native American mitochondrial DNA analysis indicates that the Amerind and the Nadene populations were founded by two independent migrations. Genetics. 1992 Jan;130(1):153–162. [PMC free article] [PubMed]
  • Torroni A, Sukernik RI, Schurr TG, Starikorskaya YB, Cabell MF, Crawford MH, Comuzzie AG, Wallace DC. mtDNA variation of aboriginal Siberians reveals distinct genetic affinities with Native Americans. Am J Hum Genet. 1993 Sep;53(3):591–608. [PMC free article] [PubMed]
  • Troup GM, Schanfield MS, Singaraju CH, Harvey RL, Jameson J, Capper J, Baker B. Study of HLA alloantigens of the Navajo Indians of North America. II. HLA-A, B, C, DR and other genetic markers. Tissue Antigens. 1982 Nov;20(5):339–351. [PubMed]
  • Vigilant L, Pennington R, Harpending H, Kocher TD, Wilson AC. Mitochondrial DNA sequences in single hairs from a southern African population. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9350–9354. [PMC free article] [PubMed]
  • Vullo CM, Celis EM, Serra HM, Riera CM. Study of HLA system in a Mataco population: a geographically isolated American Indian tribe. Tissue Antigens. 1984 Jan;23(1):33–40. [PubMed]
  • Wallace DC, Garrison K, Knowler WC. Dramatic founder effects in Amerindian mitochondrial DNAs. Am J Phys Anthropol. 1985 Oct;68(2):149–155. [PubMed]
  • Wallace DC, Torroni A. American Indian prehistory as written in the mitochondrial DNA: a review. Hum Biol. 1992 Jun;64(3):403–416. [PubMed]
  • Wallace DC, Ye JH, Neckelmann SN, Singh G, Webster KA, Greenberg BD. Sequence analysis of cDNAs for the human and bovine ATP synthase beta subunit: mitochondrial DNA genes sustain seventeen times more mutations. Curr Genet. 1987;12(2):81–90. [PubMed]
  • Ward RH, Frazier BL, Dew-Jager K, Päbo S. Extensive mitochondrial diversity within a single Amerindian tribe. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8720–8724. [PMC free article] [PubMed]
  • Ward RH, Gershowitz H, Layrisse M, Neel JV. The genetic structure of a tribal population, the Yanomama Indians XI. Gene frequencies for 10 blood groups and the ABH-Le secretor traits in the Yanomama and their neighbors; the uniqueness of the tribe. Am J Hum Genet. 1975 Jan;27(1):1–30. [PMC free article] [PubMed]
  • Williams RC, Morse HG, Bonnell MD, Rate RG, Kuberski TT. The HLA loci of th Hopi and Navajo. Am J Phys Anthropol. 1981 Nov;56(3):291–296. [PubMed]
  • Williams RC, Steinberg AG, Gershowitz H, Bennett PH, Knowler WC, Pettitt DJ, Butler W, Baird R, Dowda-Rea L, Burch TA, et al. GM allotypes in Native Americans: evidence for three distinct migrations across the Bering land bridge. Am J Phys Anthropol. 1985 Jan;66(1):1–19. [PubMed]
  • Wrischnik LA, Higuchi RG, Stoneking M, Erlich HA, Arnheim N, Wilson AC. Length mutations in human mitochondrial DNA: direct sequencing of enzymatically amplified DNA. Nucleic Acids Res. 1987 Jan 26;15(2):529–542. [PMC free article] [PubMed]

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