* Department of Evolutionary Biology, Institute of Molecular and Cell Biology, University of Tartu and Estonian Biocentre, Tartu, Estonia; Genetics Laboratory, Institute of Biological Problems of the North, Russian Academy of Sciences, Magadan, Russia;
Institute of Medical Genetics, Tomsk Research Center, Russian Academy of Medical Sciences, Tomsk, Russia;
Institute for Anthropological Research, Zagreb, Croatia; || Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow, Russia; ¶ Kharkov Clinical Genetic and Prenatal Diagnostics Center, Kharkov, Ukraine; # Institute of Biochemistry and Genetics, Ufa Research Center, Russian Academy of Sciences, Ufa, Russia; ** Laboratoire d'Etude du Polymorphisme de l'ADN, Faculté de Médecine, Nantes, France;
Institute of Molecular Biology and Biotechnology and Department of Basic Sciences, University of Athens School of Medicine, Athens, Greece;
Department of Forensic Sciences and Toxicology, University of Crete School of Medicine, Heraklion, Greece;
Laboratoire de Génétique Moléculaire, Institut Universitaire de Recherche Clinique IURC et CHU, Montpellier, France; |||| Department of Physiology, University of Kiel, Kiel, Germany; ¶¶ Department of Biology, Faculty of Natural Sciences, Tirana University, Tirana, Albania; and ## Department of Medical Laboratory Sciences, Kuwait University, Sulaibikhat, Kuwait
Correspondence: E-mail: evall{at}ut.ee.
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Abstract |
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Key Words: human mitochondrial DNA population genetics phylogeography
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Introduction |
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Materials and Methods |
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The samples were selected at random from nine populations: 50 Finno-Ugric speakers from the Volga-Ural region (10 Udmurts, 10 Mokshas, 16 Erzyas, 7 Permyak Komis, 7 Zyrian Komis); 50 Estonians; 165 Eastern Slavs (127 Russians, 38 Ukrainians from various districts of Russia and the Ukraine); 50 Slovaks; 50 French from southern France, Lyon, Low Normandy, and Poitiers; 50 individuals from the Balkans (17 Croats, 17 Albanians, 16 Greeks); 50 Turks; 50 individuals from the Near and the Middle East (10 Jordanians, 8 Lebanese, 7 Saudis, 12 Syrians, 13 Iranians); 48 individuals from Central Asia (17 Altaians, 11 Kirghiz, 3 Kazakhs, 11 Tajiks, 6 Uzbeks). Sixteen Russian and six Ukrainian HVS-I sequences have been published by Malyarchuk and Derenko (2001a), 33 Russian HVS-I and second hypervariable segment (HVS-II) sequences by Malyarchuk et al. (2002), and all of the Volga-Ural region mtDNA HVS-I sequences by Bermisheva et al. (2002). All the samples harbored a C at nucleotide position (np) 7028, which is diagnostic for Hg H and was inferred from the absence of the AluI restriction site at np 7025 (Torroni et al. 1994). All mutations and position numbers in this study are given with respect to Anderson et al. (1981) as revised by Andrews et al. (1999).
Four hundred forty-eight samples were screened for 14 polymorphisms in the mtDNA coding region and three in HVS-II in addition to HVS-I sequence variation. A hierarchical strategy was applied to 104 Russian and 11 Ukrainian mtDNAs (Appendix S2 in the Supplementary Material online). HVS-I variation for all of the samples was scored between nps 1602416383. Nucleotide changes at positions 73, 951, 3010, 4336, 4452, 4769, 4793, 5004, 8448, 9066, 9380, 13101, 13759, and 16482 were determined by restriction fragment length polymorphisms (RFLPs; Appendixes S1 and S2). Nucleotide states at positions 239, 456, 3915, and 6776 were detected by direct sequencing or allele-specific polymerase chain reaction (PCR; Appendixes S1 and S2). Nucleotide positions 239 and 3915 were sequenced in samples having 16362C and/or lacking a Hin6I restriction site at np 9380 and/or having a DdeI site at np 16478. We note that the transition at np 239 nearly always occurs with the 16362C allele, as it was not found in Hg H variants with 16362T in 2,350 published HVS-II sequences (Hofmann et al. 1997; Parson et al. 1998; Dimo-Simonin et al. 2000; Malyarchuk et al. 2003; Vanecek, Vorel, and Sip 2004; Pereira, Cunha, and Amorim 2004). Credible regions of the obtained haplogroup frequencies were computed with the Sampling program kindly provided by Vincent Macaulay.
The phylogeny of the samples was studied by the construction of a reduced median network (fig. 2A). In the network analysis 479 samples were included (see Appendix S1), including the 31 Finnish sequences taken from Finnilä, Lehtonen, and Majamaa (2001), while 115 Eastern Slav mtDNAs, which were analyzed hierarchically (see Appendix S2), have not been included. The reduced median network (Bandelt et al. 1995; rho set at 2) was constructed with the Network 4.0.0.0. program (Fluxus Technology Ltd., Clare, Suffolk, UK, http://www.fluxus-engineering.com) followed by a median joining algorithm (Bandelt, Forster, and Röhl 1999; epsilon set at 0), as explained at the Fluxus-Engineering Web site. Nucleotide positions were divided into three classes of transition ratesfast (16093, 16129, 16189, 16304, 16311, and 16362), intermediate (16172, 16209, 16278, 16293), and slow (the remainder of the positions between 16024 and 16383)and assigned class weights 1, 2, and 4, respectively. Transversions and coding region mutations were weighted 8.
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Altogether, 830 mitochondrial genomes were included in the coalescence analysis. A subset of the obtained coalescence estimates are presented in table 1 and all of the results in table S1. An average transitional distance from the root haplotype (rho) was calculated. Coalescence time has been calculated taking one transitional step between nucleotide positions 1609016365 ("HVS") equal to 20,180 years (Forster et al. 1996) and one base substitution between nucleotide positions 57716023 ("coding") equal to 5,138 years (Mishmar et al. 2003). Standard deviation of the rho estimate (sigma) was calculated as in Saillard et al. (2000b), and SD denotes the deviation in years. The 115 Eastern Slav samples analyzed hierarchically and not shown in figure 2A have been included in the coalescence analysis. Note that the coding sequence data is derived mainly from European populations.
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Results and Discussion |
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One hundred twenty-five variable positions were detected in 594 (563 + 31 Finnish sequences of Finnilä, Lehtonen, and Majamaa 2001) Hg H HVS-I sequences. Among them, recurrent transitions were observed in 50 positions (40%) in different subclades (table 2). The sites with the highest number of recurrences match the HVS-I hot-spot sites identified previously (Hasegawa et al. 1993; Malyarchuk and Derenko 2001b; Allard et al. 2002). The most variable positions, 16093 and 16311, had received parallel hits in seven different subclusters; 16189 in six; 16092, 16304, and 16362 each in five; and 16129, 16209, 16249, and 16325 each in four subclusters. Another 12 HVS-I mutations were found in three and 28 substitutions in two different phylogenetic contexts. Because quite a few of these hot-spot mutations are present in HVS-I haplotypes that have been highlighted as having founder status in Europe (Richards et al. 2000), our results document again that additional coding region information is essential and unavoidable in defining monophyletic subclades of Hg H reliably (Torroni et al. 1993; Bandelt et al. 2001; Kivisild et al. 2002). We also found that a reversion of A to the ancestral base G at np 73 of the HVS-II, noticed in Hg H first by Torroni et al. (1996), has occurred independently at least four times in Hg H phylogeny (see also Helgason et al. 2000).
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Sub-Hg H4 was previously defined by an array of eight mutations (nps 3992, 4024, 5004, 8269, 9123, 10044, 14365, and 14582) through an analysis of haplotypes that occurred in at least two individuals (Herrnstadt et al. 2002). However, re-examination of the sequence data of Herrnstadt et al. (2002) revealed that only six mutations at nps 3992, 4024, 5004, 9123, 14365, and 14582 appear to be necessary to characterize the clade (fig. S1). Consequently, here we name the bough defined by a G-to-A mutation at np 8269, which further embraces the 10044 twig, as H4a.
While applying the RFLP method we discovered three previously unknown mutations: a transition at np 13760 abolishing the AciI site at np 13757 defining sub-Hg H11, a transition at np 5005 eliminating the H4-defining DdeI site at np 5003, and a transition at np 8449 eliminating the H11-defining np 8446 SspI site. Therefore, we confirmed the presence of H4-specific T at np 5004 by sequencing the position in all 12 samples lacking the DdeI 5003 site. The monophyly of sub-Hg H11 is well established by the combination of two RFLPs and by the characteristic HVS-I mutation pattern. These results show that classical indirect DNA polymorphism detection methods, like RFLP, should be backed-up by direct sequencing in order to avoid the ambiguous or even erroneous inference of phylogeny.
The next paragraphs address the main phylogeographic results. The largest subcluster is sub-Hg H1, which comprises about 30% of Hg H and 13% of the total European mtDNA pool. H1 is most frequent in the Iberian Peninsula, covering about 46% of local Hg H lineages (Pereira et al. 2004; Quintans et al. 2004). In the Near East the frequency of H1 does not exceed 6% (P < .025), and its relative frequency with respect to Hg H is lower than that seen in Europe (14%). In the Central Asian populations, where Hg H makes up about 11% of the local mtDNA pool, only 6% of H samples belong to sub-Hg H1 (table 3).
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Like H1b, sub-Hg H2a occurs more frequently (P < .05) in Eastern than in Western European Hg H genomes, 6.5% and 1.1%, respectively, when averaged over populations (table 3 and fig. 2B). The spread of H2a extends to Central Asia, mimicking to some extent, albeit at a lower frequency, the phylogeography of Y-chromosomal Hg R1a (Rosser et al. 2000; Wells et al. 2001). In contrast, sub-Hg H3 was found to be more frequent (P < .05) in the Western (11.7%) than in the Eastern European Hg H pool (4.1%) and is virtually absent in Anatolia and the Near East (fig. 2B), resembling in its phylogeography the spread of Y-chromosomal Hg R1b associated 49a,f TaqI haplotype 15 (Semino et al. 1996; Cinnioglu et al. 2004). The high frequency of mtDNA Hg H3in combination with Y chromosomal Ht 15extends to the Iberian Peninsula, where H3 constitutes about 17% of Hg H and is the highest detected so far (Pereira et al. 2004; Quintans et al. 2004).
The coalescence ages of H2a1 and H3 fall to the period of postglacial recolonization in Europe (table 1), suggested first for mtDNA Hg V (Torroni et al. 1998, 2001a). We also note that mtDNA bearing "St. Luke motif," 1623516293 (Vernesi et al. 2001), belong to sub-Hg H2 (fig. 2A), being particularly frequent in Germany and Scotland (Helgason et al. 2001; Pfeiffer et al. 2001).
The Near Eastern samples cluster together with Central Asian mtDNAs in the sub-Hgs H6b and H8, which are very rare in Europe. The finding is demonstrating a separate flow of maternal lineages south of the Caspian and the Black Sea in addition to well-known long-lasting migrations of pastoral nomads alongside the steppe belt that connects the Danube Basin, over the Pontic-Caspian, with Central Asia, Altay, and Manchuria.
In contrast to that found in Europeans, sub-Hgs H6 and H8 among Central Asian/Altaian populations are characterized by distinctly divergent haplotypes (fig. 2A). This finding may reflect a long-time separation of Asian and European H6 and H8 mtDNA pools and/or an earlier expansion of H6 in the eastern part of its present range. Indeed, the coalescence age of H6 in Central Asians is very deep40,400 years (SD 16,400 years; table S1). Because the Asian branches of sub-Hg H6 are highly divergent and seem to be among the oldest in Hg H (table S1), they pose an interesting problem, deserving specific study with a much larger sample size at hand.
The commonly used HVS-I clock (Forster et al. 1996) places the initial expansion of Hg H in the Near East to about 23,000 to 28,000 years before the present (Richards et al. 2000). The ancestral clades of Hg H, pre-HV, and HV* have their combined present range predominantly in the Near and Middle East, and in the Caucasus (Metspalu et al. 1999; Richards et al. 2002), implying this could have been the region where the pre-HV/HV clade started to diversify and, possibly, where the earliest Hg H variants might have first appeared.
However, most subclusters of Hg H exhibit coalescence ages, corresponding to the beginning of their expansion in the Late Upper Paleolithic (tables 1 and S1). In this respect our results support an earlier proposition that Hg H was the major mtDNA haplogroup participating in the recolonization of Europe after the Last Glacial Maximum (Torroni et al. 1998; Richards et al. 2000). It is also important to note that the expansion time estimates derived from the coding region and HVS-I of Hg H are often in reasonable agreement with each other (tables 1 and S1). Sub-Hgs H1 and H3 have their highest frequencies in the Iberian Peninsula. These sub-Hgs may have been the companions of mtDNA Hg V in the postglacial repeopling of Europe from a refuge area in Iberia (Torroni et al. 1998). However, in contrast to Hg V, suggested coalescence ages of H1 and H313,400 ± 3,000 and 8,600 ± 2,800 years ago, respectively (Pereira et al. 2004)do not imply deeper phylogeny of H1 and H3 in Iberia compared to the rest of Europe (tables 1 and S1).
These results demonstrate that a seemingly uniform spread of this major human mtDNA clade in western Eurasian populations hides within itself a complex structure of phylogeographically informative subclades. However, it is evident that additional knowledge at the level of complete mtDNA sequences is still needed for a truly comprehensive cataloguing of Hg H diversity, in particular more effectively covering its variation in the Mediterranean, Near and Middle Eastern, and Central Asian/Altaian populations. Nevertheless, even now it is tempting to speculate that much deeper coalescence ages, close to/overlapping with the boundary between the Middle and Upper Paleolithic, for some Hg H branches in Central Asian/Altaian populations, suggest that the time depth of this predominant haplogroup may be much deeper than its apparent general signal for expansion in Europe. It is, therefore, possible that the carriers of pre-Aurignacian industry identified in Zagros as well as in Altay (Otte and Derevianko 2001) were anatomically modern humans already possessing Hg H.
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Supplementary Material |
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Acknowledgements |
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Footnotes |
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Lisa Matisoo-Smith, Associate Editor
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References |
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---|
Allard, M. W., K. Miller, M. Wilson, K. Monson, and B. Budowle. 2002. Characterization of the Caucasian haplogroups present in the SWGDAM forensic mtDNA dataset for 1771 human control region sequences. Scientific Working Group on DNA Analysis Methods. J. Forensic Sci. 47:12151223.[ISI][Medline]
Anderson, S., A. T. Bankier, B. G. Barrell et al. (14 co-authors). 1981. Sequence and organization of the human mitochondrial genome. Nature 290:457465.[ISI][Medline]
Andrews, R. M., I. Kubacka, P. F. Chinnery, R. N. Lightowlers, D. M. Turnbull, and N. Howell. 1999. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat. Genet. 23:147.[CrossRef][ISI][Medline]
Arnason, U., X. Xu, and A. Gullberg. 1996. Comparison between the complete mitochondrial DNA sequences of Homo and the common chimpanzee based on nonchimeric sequences. J. Mol. Evol. 42:145152.[ISI][Medline]
Bamshad, M., T. Kivisild, W. S. Watkins et al. (18 co-authors). 2001. Genetic evidence on the origins of Indian caste populations. Genome Res. 11:9941004.
Bandelt, H.-J., P. Forster, and A. Röhl. 1999. Median-joining networks for inferring intraspecific phylogenies. Mol. Biol. Evol. 16:3748.[Abstract]
Bandelt, H.-J., P. Forster, B. C. Sykes, and M. B. Richards. 1995. Mitochondrial portraits of human populations using median networks. Genetics 141:743753.
Bandelt, H. J., P. Lahermo, M. Richards, and V. Macaulay. 2001. Detecting errors in mtDNA data by phylogenetic analysis. Int. J. Legal Med. 115:6469.[CrossRef][ISI][Medline]
Bermisheva, M., K. Tambets, R. Villems, and E. Khusnutdinova. 2002. Diversity of mitochondrial DNA haplotypes in ethnic populations of the Volga-Ural region of Russia. Mol. Biol. (Mosk) 36:9901001.[Medline]
Cinnioglu, C., R. King, T. Kivisild et al. (15 co-authors). 2004. Excavating Y-chromosome haplotype strata in Anatolia. Hum. Genet. 114:127148.[CrossRef][ISI][Medline]
Comas, D., F. Calafell, E. Mateu et al. (12 co-authors). 1998. Trading genes along the silk road: mtDNA sequences and the origin of Central Asian populations. Am. J. Hum. Genet. 63:18241838.[CrossRef][ISI][Medline]
Corte-Real, H. B., V. A. Macaulay, M. B. Richards, G. Hariti, M. S. Issad, A. Cambon-Thomsen, S. Papiha, J. Bertranpetit, and B. C. Sykes. 1996. Genetic diversity in the Iberian Peninsula determined from mitochondrial sequence analysis. Ann. Hum. Genet. 60:331350.[ISI][Medline]
de la Chapelle, A., and F. A. Wright. 1998. Linkage disequilibrium mapping in isolated populations: the example of Finland revisited. Proc. Natl. Acad. Sci. USA 95:1241612423.
Derbeneva, O. A., E. B. Starikovskaya, D. C. Wallace, and R. I. Sukernik. 2002a. Traces of early Eurasians in the Mansi of northwest Siberia revealed by mitochondrial DNA analysis. Am. J. Hum. Genet. 70:10091014.[CrossRef][ISI][Medline]
Derbeneva, O. A., R. I. Sukernik, N. V. Volodko, S. H. Hosseini, M. T. Lott, and D. C. Wallace. 2002b. Analysis of mitochondrial DNA diversity in the Aleuts of the Commander Islands and its implications for the genetic history of Beringia. Am. J. Hum. Genet. 71:415421.[CrossRef][Medline]
Derenko, M. V., T. Grzybowski, B. A. Malyarchuk et al. (11 co-authors). 2003. Diversity of mitochondrial DNA lineages in south Siberia. Ann. Hum. Genet. 67:391411.[CrossRef][ISI][Medline]
Dimo-Simonin, N., F. Grange, F. Taroni, C. Brandt-Casadevall, and P. Mangin. 2000. Forensic evaluation of mtDNA in a population from south west Switzerland. Int. J. Legal Med. 113:8997.[ISI][Medline]
Finnilä, S., I. E. Hassinen, L. Ala-Kokko, and K. Majamaa. 2000. Phylogenetic network of the mtDNA haplogroup U in Northern Finland based on sequence analysis of the complete coding region by conformation-sensitive gel electrophoresis. Am. J. Hum. Genet. 66:10171026.[CrossRef][ISI][Medline]
Finnilä, S., M. S. Lehtonen, and K. Majamaa. 2001. Phylogenetic network for European mtDNA. Am. J. Hum. Genet. 68:14751484.[CrossRef][ISI][Medline]
Finnilä, S., and K. Majamaa. 2001. Phylogenetic analysis of mtDNA haplogroup TJ in a Finnish population. J. Hum. Genet. 46:6469.[CrossRef][ISI][Medline]
Forster, P., R. Harding, A. Torroni, and H.-J. Bandelt. 1996. Origin and evolution of Native American mtDNA variation: a reappraisal. Am. J. Hum. Genet. 59:935945.[ISI][Medline]
Hasegawa, M., A. Di Rienzo, T. D. Kocher, and A. C. Wilson. 1993. Toward a more accurate time scale for the human mitochondrial DNA tree. J. Mol. Evol. 37:347354.[ISI][Medline]
Helgason, A., E. Hickey, S. Goodacre, V. Bosnes, K. Stefansson, R. Ward, and B. Sykes. 2001. mtDNA and the islands of the North Atlantic: estimating the proportions of Norse and Gaelic ancestry. Am. J. Hum. Genet. 68:723737.[CrossRef][ISI][Medline]
Helgason, A., S. Sigurdadottir, J. Gulcher, R. Ward, and K. Stefanson. 2000. mtDNA and the origins of the Icelanders: deciphering signals of recent population history. Am. J. Hum. Genet. 66:9991016.[CrossRef][ISI][Medline]
Herrnstadt, C., J. L. Elson, E. Fahy et al. (11 co-authors). 2002. Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups. Am. J. Hum. Genet. 70:11521171.[CrossRef][ISI][Medline]
Herrnstadt, C., G. Preston, and N. Howell. 2003. Errors, phantoms and otherwise, in human mtDNA sequences. Am. J. Hum. Genet. 72:15851586.[CrossRef][ISI][Medline]
Hofmann, S., M. Jaksch, R. Bezold, S. Mertens, S. Aholt, A. Paprotta, and K. D. Gerbitz. 1997. Population genetics and disease susceptibility: characterization of central European haplogroups by mtDNA gene mutations, correlation with D loop variants and association with disease. Hum. Mol. Genet. 6:18351846.
Ingman, M., H. Kaessmann, S. Pääbo, and U. Gyllensten. 2000. Mitochondrial genome variation and the origin of modern humans. Nature 408:708713.[CrossRef][ISI][Medline]
Kittles, R. A., A. W. Bergen, M. Urbanek, M. Virkkunen, M. Linnoila, D. Goldman, and J. C. Long. 1999. Autosomal, mitochondrial, and Y chromosome DNA variation in Finland: evidence for a male-specific bottleneck. Am. J. Phys. Anthropol. 108:381399.[CrossRef][ISI][Medline]
Kivisild, T., M. J. Bamshad, K. Kaldma et al. (15 co-authors). 1999. Deep common ancestry of Indian and western-Eurasian mitochondrial DNA lineages. Curr. Biol. 9:13311334.[CrossRef][ISI][Medline]
Kivisild, T., S. Rootsi, M. Metspalu et al. (18 co-authors). 2003. The genetic heritage of the earliest settlers persists both in Indian tribal and caste populations. Am. J. Hum. Genet. 72:313332.[CrossRef][ISI][Medline]
Kivisild, T., H.-V. Tolk, J. Parik, Y. Wang, S. S. Papiha, H.-J. Bandelt, and R. Villems. 2002. The emerging limbs and twigs of the East Asian mtDNA tree. Mol. Biol. Evol. 19:17371751.
Kong, Q. P., Y. G. Yao, C. Sun, H. J. Bandelt, C. L. Zhu, and Y. P. Zhang. 2003. Phylogeny of east Asian mitochondrial DNA lineages inferred from complete sequences. Am. J. Hum. Genet. 73:671676.[CrossRef][ISI][Medline]
Levin, B. C., H. Cheng, and D. J. Reeder. 1999. A human mitochondrial DNA standard reference material for quality control in forensic identification, medical diagnosis, and mutation detection. Genomics 55:135146.[CrossRef][ISI][Medline]
Maca-Meyer, N., A. M. Gonzalez, J. M. Larruga, C. Flores, and V. M. Cabrera. 2001. Major genomic mitochondrial lineages delineate early human expansions. BMC Genet. 2:13.[CrossRef][Medline]
Macaulay, V. A., M. B. Richards, E. Hickey, E. Vega, F. Cruciani, V. Guida, R. Scozzari, B. Bonné-Tamir, B. Sykes, and A. Torroni. 1999. The emerging tree of West Eurasian mtDNAs: a synthesis of control-region sequences and RFLPs. Am. J. Hum. Genet. 64:232249.[CrossRef][ISI][Medline]
Malyarchuk, B. A., and M. V. Derenko. 2001a. Mitochondrial DNA variability in Russians and Ukrainians: implications to the origin of the Eastern Slavs. Ann. Hum. Genet. 65:6378.[CrossRef][ISI][Medline]
Malyarchuk, B. A., and M. V. Derenko. 2001b. Variation of human mitochondrial DNA: distribution of hot spots in hypervariable segment I of the major noncoding region. Genetika 37:9911001.[Medline]
Malyarchuk, B. A., T. Grzybowski, M. V. Derenko, J. Czarny, K. Drobnic, and D. Miscicka-Sliwka. 2003. Mitochondrial DNA variability in Bosnians and Slovenians. Ann. Hum. Genet. 67:412425.[CrossRef][ISI][Medline]
Malyarchuk, B. A., T. Grzybowski, M. V. Derenko, J. Czarny, M. Wozniak, and D. Miscicka-Sliwka. 2002. Mitochondrial DNA variability in Poles and Russians. Ann. Hum. Genet. 66:261283.[CrossRef][ISI][Medline]
Marzuki, S., A. S. Noer, P. Lertrit, D. Thyagarajan, R. Kapsa, P. Utthanaphol, and E. Byrne. 1991. Normal variants of human mitochondrial DNA and translation products: the building of a reference data base. Hum. Genet. 88:139145.[CrossRef][ISI][Medline]
Meinilä, M., S. Finnilä, and K. Majamaa. 2001. Evidence for mtDNA admixture between the Finns and the Saami. Hum. Hered. 52:160170.[CrossRef][ISI][Medline]
Metspalu, E., T. Kivisild, K. Kaldma, J. Parik, M. Reidla, K. Tambets, and R. Villems. 1999. The Trans-Caucasus and the expansion of the Caucasoid-specific human mitochondrial DNA. Pp. 121134 in S. Papiha, R. Deka, and R. Chakraborty, eds. Genomic diversity: application in human population genetics. Kluwer Academic/Plenum Publishers, New York.
Mishmar, D., E. Ruiz-Pesini, P. Golik et al. (13 co-authors). 2003. Natural selection shaped regional mtDNA variation in humans. Proc. Natl. Acad. Sci. USA 100:171176.
Nevanlinna, H. R. 1972. The Finnish population structure. A genetic and genealogical study. Hereditas 71:195236.[Medline]
Otte M., and A. Derevianko. 2001. The Aurignacian in Altai. Antiquity 75:4448.[ISI]
Parson, W., T. J. Parsons, R. Scheithauer, and M. M. Holland. 1998. Population data for 101 Austrian Caucasian mitochondrial DNA d-loop sequences: application of mtDNA sequence analysis to a forensic case. Int. J. Legal Med. 111:124132.[CrossRef][ISI][Medline]
Passarino, G., O. Semino, L. F. Bernini, and A. S. Santachiara-Benerecetti. 1996. Pre-Caucasoid and Caucasoid genetic features of the Indian population, revealed by mtDNA polymorphisms. Am. J. Hum. Genet. 59:927934.[ISI][Medline]
Peltonen, L., A. Palotie, and K. Lange. 2000. Use of population isolates for mapping complex traits. Nat. Rev. Genet. 1:182190.[CrossRef][ISI][Medline]
Pereira L., C. Cunha, and A. Amorim. 2004. Predicting sampling saturation of mtDNA haplotypes: an application to an enlarged Portuguese database. Int. J. Legal. Med. 118:132136.[CrossRef][ISI][Medline]
Pereira, L., M. Richards, A. Alonso, C. Albarran, O. Garcia, V. Macaulay, and A. Amorim. 2004. Subdividing mtDNA haplogroup H based on coding-region polymorphismsa study in Iberia. Int. Congr. Ser. 1261:416418.[CrossRef]
Pfeiffer, H., P. Forster, C. Ortmann, and B. Brinkmann. 2001. The results of an mtDNA study of 1,200 inhabitants of a German village in comparison to other Caucasian databases and its relevance for forensic casework. Int. J. Legal Med. 114:169172.[CrossRef][ISI][Medline]
Piercy, R., K. M. Sullivan, N. Benson, and P. Gill. 1993. The application of mitochondrial DNA typing to the study of white Caucasian genetic identification. Int. J. Legal Med. 106:8590.[ISI][Medline]
Polyak, K., Y. Li, H. Zhu, C. Lengauer, J. K. Willson, S. D. Markowitz, M. A. Trush, K. W. Kinzler, and B. Vogelstein. 1998. Somatic mutations of the mitochondrial genome in human colorectal tumours. Nat. Genet. 20:291293.[CrossRef][ISI][Medline]
Quintans, B., V. Alvarez-Iglesias, A. Salas, C. Phillips, M. V. Lareu, and A. Carracedo. 2004. Typing of mitochondrial DNA coding region SNPs of forensic and anthropological interest using SNaPshot minisequencing. Forensic Sci. Int. 140:251257.[CrossRef][ISI][Medline]
Rando, J. C., F. Pinto, A. M. Gonzalez, M. Hernandez, J. M. Larruga, V. M. Cabrera, and H. J. Bandelt. 1998. Mitochondrial DNA analysis of northwest African populations reveals genetic exchanges with European, Near-Eastern, and sub-Saharan populations. Ann. Hum. Genet. 62:531550.[CrossRef][ISI]
Reid, F. M., G. A. Vernham, and H. T. Jacobs. 1994. Complete mtDNA sequence of a patient in a maternal pedigree with sensorineural deafness. Hum. Mol. Genet. 3:14351436.[ISI][Medline]
Reidla, M., T. Kivisild, E. Metspalu et al. (43 co-authors). 2003. Origin and diffusion of mtDNA haplogroup X. Am. J. Hum. Genet. 73:11781190.[CrossRef][ISI][Medline]
Richards, M., H. Corte-Real, P. Forster, V. Macaulay, H. Wilkinson-Herbots, A. Demaine, S. Papiha, R. Hedges, H.-J. Bandelt, and B. Sykes. 1996. Paleolithic and neolithic lineages in the European mitochondrial gene pool. Am. J. Hum. Genet. 59:185203.[ISI][Medline]
Richards, M., V. Macaulay, E. Hickey et al. (26 co-authors). 2000. Tracing European founder lineages in the Near Eastern mtDNA pool. Am. J. Hum. Genet. 67:12511276.[ISI][Medline]
Richards, M., V. Macaulay, A. Torroni, and H. J. Bandelt. 2002. In search of geographical patterns in European mitochondrial DNA. Am. J. Hum. Genet. 71:11681174.[CrossRef][ISI][Medline]
Richards, M. B., V. A. Macaulay, H.-J. Bandelt, and B. C. Sykes. 1998. Phylogeography of mitochondrial DNA in western Europe. Ann. Hum. Genet. 62:241260.[CrossRef][ISI][Medline]
Rieder, M. J., S. L. Taylor, V. O. Tobe, and D. A. Nickerson. 1998. Automating the identification of DNA variations using quality-based fluorescence re-sequencing: analysis of the human mitochondrial genome. Nucleic Acids Res. 26:967973.
Rosser, Z. H., T. Zerjal, M. E. Hurles et al. (63 co-authors). 2000. Y-chromosomal diversity in Europe is clinal and influenced primarily by geography, rather than by language. Am. J. Hum. Genet. 67:15261543.[CrossRef][ISI][Medline]
Saillard, J., I. Evseva, L. Tranebjaerg, and S. Norby. 2000a. Mitochondrial DNA diversity among Nenets. Pp. 255258 in C. Renfrew and K. Boyle, eds. Archaeogenetics: DNA and and the population prehistory of Europe. McDonald Institute for Archaeological Research Monograph Series, Cambridge University, Cambridge.
Saillard, J., P. Forster, N. Lynnerup, H.-J. Bandelt, and S. Nørby. 2000b. mtDNA variation among Greenland Eskimos: the edge of the Beringian expansion. Am. J. Hum. Genet. 67:718726.[CrossRef][ISI][Medline]
Semino, O., G. Passarino, A. Brega, M. Fellous, and A. S. Santachiara-Benerecetti. 1996. A view of the neolithic demic diffusion in Europe through two Y chromosome-specific markers. Am. J. Hum. Genet. 59:964968.[ISI][Medline]
Stevanovitch, A., A. Gilles, E. Bouzaid, R. Kefi, F. Paris, R. P. Gayraud, J. L. Spadoni, F. El-Chenawi, and E. Beraud-Colomb. 2004. Mitochondrial DNA sequence diversity in a sedentary population from Egypt. Ann. Hum. Genet. 68:2339.[CrossRef][ISI][Medline]
Tambets, K., T. Kivisild, E. Metspalu et al. (13 co-authors). 2000. The topology of the maternal lineages of the Anatolian and Trans-Caucasus populations and the peopling of the Europe: some preliminary considerations. Pp. 219235 in C. Renfrew and K. Boyle, eds. Archaeogenetics: DNA and the population prehistory of Europe. Cambridge University Press, Cambridge.
Tambets, K., S. Rootsi, T. Kivisild et al. (46 co-authors). 2004. The western and eastern Roots of the Saamithe story of genetic "outliers" told by mitochondrial DNA and Y chromosomes. Am. J. Hum. Genet. 74:661682.[CrossRef][Medline]
Torroni, A., H.-J. Bandelt, L. D'Urbano et al. (11 co-authors). 1998. mtDNA analysis reveals a major late Paleolithic population expansion from southwestern to northeastern Europe. Am. J. Hum. Genet. 62:11371152.[CrossRef][ISI][Medline]
Torroni, A., H. J. Bandelt, V. Macaulay et al. (33 co-authors). 2001a. A signal, from human mtDNA, of postglacial recolonization in Europe. Am. J. Hum. Genet. 69:844852.[CrossRef][ISI][Medline]
Torroni, A., K. Huoponen, P. Francalacci, M. Petrozzi, L. Morelli, R. Scozzari, D. Obinu, M. L. Savontaus, and D. C. Wallace. 1996. Classification of European mtDNAs from an analysis of three European populations. Genetics 144:18351850.
Torroni, A., M. T. Lott, M. F. Cabell, Y. S. Chen, L. Lavergne, and D. C. Wallace. 1994. mtDNA and the origin of Caucasians: identification of ancient Caucasian-specific haplogroups, one of which is prone to a recurrent somatic duplication in the D-loop region. Am. J. Hum. Genet. 55:760776.[ISI][Medline]
Torroni, A., C. Rengo, V. Guida et al. (12 co-authors). 2001b. Do the four clades of the mtDNA haplogroup L2 evolve at different rates? Am. J. Hum. Genet. 69:13481356.[CrossRef][ISI][Medline]
Torroni, A., R. I. Sukernik, T. G. Schurr, Y. B. Starikorskaya, M. F. Cabell, M. H. Crawford, A. G. Comuzzie, and D. C. Wallace. 1993. mtDNA variation of aboriginal Siberians reveals distinct genetic affinities with Native Americans. Am. J. Hum. Genet. 53:591608.[ISI][Medline]
Vanecek, T., F. Vorel, and M. Sip. 2004. Mitochondrial DNA D-loop hypervariable regions: Czech population data. Int. J. Legal Med. 118:1418.[CrossRef][ISI][Medline]
Vernesi, C., G. Di Benedetto, D. Caramelli, E. Secchieri, L. Simoni, E. Katti, P. Malaspina, A. Novelletto, V. T. Marin, and G. Barbujani. 2001. Genetic characterization of the body attributed to the evangelist Luke. Proc. Natl. Acad. Sci. USA 98:1346013463. Epub 12001 Oct 13416.
Wells, R. S., N. Yuldasheva, R. Ruzibakiev et al. (27 co-authors). 2001. The Eurasian heartland: a continental perspective on Y-chromosome diversity. Proc. Natl. Acad. Sci. USA 98:1024410249.