Molecular Biology, Vol. 36, No. 6, 2002, pp. 802Ð812. Translated from Molekulyarnaya Biologiya, Vol. 36, No. 6, 2002, pp. 990Ð1001. Original Russian Text Copyright © 2002 by Bermisheva, Tambets, Villems, Khusnutdinova.

GENOMICS. TRANSCRIPTOMICS. PROTEOMICS UDC 575.174.599.9 Diversity of Mitochondrial DNA in Ethnic Populations of the VolgaÐUral Region M. A. Bermisheva1, K. Tambets2, R. Villems2, and E. K. Khusnutdinova1 1 Institute of Biochemistry and Genetics, Ufa Research Center, Russian Academy of Sciences, Ufa, 450054 Russia; E-mail: [email protected] 2 Estonian Biological Center, Tartu University, Tartu, Estonia Received February 28, 2002

Abstract—The mtDNA polymorphism was analyzed in eight ethnic groups (N = 979) of the VolgaÐUral region. Most mtDNA variants belonged to haplogroups H, U, T, J, W, I, R, and N1 characteristic of West Eurasian pop- ulations. The most frequent were haplogroups H (12Ð42%) and U (18Ð44%). East Eurasian mtDNA types (A, B, Y, F, M, N9) were also observed. Genetic diversity was higher in Turkic than in Finno-Ugric populations. The frequency of mtDNA types characteristic of Siberian and Central Asian populations substantially increased in the ethnic groups living closer to the Urals, a boundary between Europe and Asia. Geographic distances, rather than linguistic barriers, were assumed to play the major role in distribution of mtDNA types in the VolgaÐ Ural region. Thus, as concerns the maternal lineage, the Finno-Ugric populations of the region proved to be more similar to their Turkic neighbors rather than to linguistically related Balto-Finnish ethnic groups.

Key words: mitochondrial DNA, haplotyping, ethnogenomics, ethnic groups of the VolgaÐUral region

INTRODUCTION Haplogroups A, B, C, and D are the first specific Asian haplogroups that have been found in native Mitochondrial (mt) DNA and the Y chromosome Americans [9, 10]. Haplogoups C and D have a com- occupy a specific place among highly polymorphic mon ancestor in cluster M, while haplogroups A and genetic systems. Owing to the maternal inheritance, B originate from cluster N. Phylogenetically, various absence of recombination, and high polymorphism, mtDNA variants specific for Eastern Eurasia may be mtDNA can be employed as a major tool in evolution- classed into several macroclusters (Fig. 1). Macro- ary, populational, and medical genetic studies [1, 2]. clusters M and N originate from African macrocluster The variation of human mtDNA has been extensively L3, the consensus nucleotide sequence of which is studied in the 1980s and 1990s. Race- and population- considered as a common ancestor (MRCA) of all non- specific mtDNA types and mutations have been African mtDNA lineages. Haplogroups of cluster M described and used to define individual haplogroups are frequent and diverse in Asia [10] and rare in [2, 3]. A modern classification of European mtDNA Europe, which supports the hypothesis that Asia was variants is based on the combined data [4Ð6] on poly- first populated as a result of migration from Eastern morphisms of the control (hypervariable segments I Africa [11]. This cluster harbors about half mtDNA and II, HVSI and HVSII) [7] and coding [8] regions of variants of the indigenous population of Eastern Eur- mtDNA. The European mtDNA clusters are best orga- asia [2], and consists of several haplogroups, includ- nized owing to detailed analysis of the mtDNA varia- ing C, Z, D, G, E, M7, M8, M9, M10, etc. (Fig. 1). Supercluster N includes haplogroups A, Y, B, and F in tion in European populations. More than 90% of Asia. A has an ancestral nucleotide (T) in European mtDNAs belong to nine haplogroups position 16,223, whereas haplogroups B and F, along (Fig. 1), which are highly specific for Western Eurasia with most European lineages, originate from cluster R. [4, 6]. These clusters are all thought to originate from one supercluster, L3n (N). In addition, supercluster Analysis of the diversity of European mtDNA vari- L3n includes several haplogroups (A, B, F, and Y) ants has been restricted to Western and Central Europe restricted to East Eurasian populations. Five haplo- so far. In this work, we characterize the mtDNA hap- groups (H, V, J, T, and U) form cluster R, which is logroup diversity in eight East European (VolgaÐUral) characterized by substitutions in mtDNA nucleotide ethnic groups representing two, Altaian and Ural, positions 12,705 and 16,223 [4]. large linguistic families.

0026-8933/02/3606-0802 $27.00 © 2002 MAIK “Nauka /Interperiodica”

MITOCHONDRIAL DNA HAPLOGROUPS 803

EXPERIMENTAL D C Material for population genetic analysis was collected during expeditions from 1989 to 2001. Z Blood of informed adults was obtained after medical M examination. In total, we tested 979 DNA specimens E of the indigenous populations of the VolgaÐUral Root region, including 221 (Trans-Ural, South- of the tree western, Northeastern, and Gaininsk Bashkirs) from L3 G the Beloretskii, Sterlibashevskii, and Ilishevskii Dis- tricts of and the Perm Region; 228 A from the Al’met’evskii and Elabuzhskii Dis- I tricts of ; 55 Chuvash from the Morgaushskii N Y District of ; 102 Mordvinians from the X

Staro-Shaiginskii District of ; 136 Mari in Eastern Eurasia B from the Zvenigovskii District of Marii El; W

101 Udmurts from the Malo-Purginskii District of in W occurring mostly R Haplogroups occurring mostly Haplogroups U and the Tatyshlinskii District of Bashkor- K F tostan; 62 Komi-Zyryans from the Sysol’skii District estern Eurasia of the ; and 74 Komi-Permyaks from J the Komi-Permyak Autonomous District. T H V Genomic DNA was isolated from 10 ml of periph- eral blood by phenolÐchloroform extraction. Frag- ment 16,024Ð16,400 of mtDNA HVSI was sequenced in a Perkin-Elmer ABI 377 DNA sequencer with a DYEnamic ET terminator cycle sequencing premix kit (Amersham Pharmacia Biotech). Fig. 1. Phylogenetic tree of mtDNA clusters found in Eur- asian populations. Haplogroups were identified by mtDNA RFLPs, including 73 (73GA) ÐAlw44I, 663 (663AG) +HaeIII, 1715 (1719GA) ÐDdeI, 4577 (4580GA) ÐNlaIII, 4643 RESULTS AND DISCUSSION (4646TC) +RsaI, 4830 (4833AG) +HaeII, 5176 (5178CA) ÐAluI, 5416 (5417 GA) +TasI, 5656 The indigenous population of the VolgaÐUral (5656AG) +NheI, 7025 (7028CT) ÐAluI, 7598 region is ethnically, historically, and culturally heter- (7600GA) ÐHhaI, 8249 (8251CT) +AvaII, 8994 ogeneous. Ethnic groups of the region belong to dif- (8994GA) ÐHaeIII, 9052 (9055GA) ÐHaeII, 10,032 ferent language groups, including the Perm (Komi- (10,034TC) +AluI, 10,394 (10,398AG) +DdeI, 10,397 Zyryans, Komi-Permyaks, Udmurts) and Volga-Finn- (10,400CT) +AluI, 12,308 (12,308AG) +HinfI, ish (Mordvinians, Mari) branches of the Ural lan- 12,406 (12,406GA) ÐHincII, 12,704 (12,705CT) guage family and the Turkic branch of the Altaian lan- −MboII, 13,262 (13,263AG) +AluI, 13,366 guage family (Bashkirs, Tatars, Chuvash). Anthropo- (13,368GA) +BamHI, 13,704 (13,708GA) ÐBstI, logically, these ethnic groups are Caucasian and have 14,068 (14,070AG) +TaqI, 14,766 (14,766TC) +MseI, a varying Mongoloid component [12]. The region and 15,904 (15,904CT) +MseI. Transition or transver- includes various geographic zones, from taiga, tundra sion resulting in a gain or loss of a restriction site is (Komi-Zyryans) and Central Volga plains (Mordvin- indicated in parentheses. Mutations in mtDNA were ians, Mari, Chuvash, Tatars) to the Southern Urals and identified according to the Cambridge reference Trans-Ural steppe (Bashkirs) (Fig. 2). sequence (CRS) [13]. To establish the phylogenetic relationships among haplotypes, median networks We sequenced the 377-bp region (16,024Ð16,400) were constructed with the combined data on polymor- of mtDNA HVSI in 979 people of the eight ethnic phisms of the mtDNA coding region and HVSI for the groups of the VolgaÐUral region. Haplogroups were total sample of the VolgaÐUral region. identified by RFLP analysis of 26 polymorphic sites of the mtDNA coding region and analysis of the dele- Genetic heterogeneity was calculated as tion from a region between the COII and tRNALys genes. Genetic heterogeneity was relatively low (0.96) 2 H = (1 – ∑xi )N/(N – 1), in Komi-Zyryans and Udmurts, and high (0.99) in Bashkirs. Mean heterogeneity of the Turkic ethnic where xi is the frequency of an mtDNA haplotype in a groups (0.98) was higher than in the Finno-Ugric eth- population and N is the sample size [14]. nic groups (0.96).

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VII

7.1

IV VIII 3.2 8.1 III 4.1 V 5.1 The Urals 5.2 3.1 VI 2.1 IX 2.2 9.1 II 6.1

1.5

1.3 1.6 1.4 I

1.2

1.1

Fig. 2. Geographic regions occupied by (1.1) Trans-Ural, (1.2) Southwestern, (1.3) Northwestern, and (1.4) Northeastern Bashkirs and (1.5) Udmurts of (I) Bashkortostan; (2.1) Kazan and (2.2) Mishari Tatars of (II) Tatarstan; (3.1) Low and (3.2) Mid-Low Chu- vash of (III) Chuvashia; (4.1) Meadow Mari of (IV) Marii El; (5.1) Erzya and (5.2) Moksha Mordvinians of (V) Mordovia; (6.1) Southern Udmurts of (VI) Udmurtia; (7.1) Komi-Zyryans of (VII) the Komi Republic; and (8.1) Komi-Permyak of (VIII) the Komi-Permyak Autonomous District.

Haplogroup-determining HVSI motifs found in the This cluster had a stellate phylogenetic tree with the VolgaÐUral populations are shown in Table 1. On evi- center occupied by the Cambridge sequence [13], dence of cluster analysis, most mtDNA types were which represents the mtDNA type most common in assigned to haplogroups specific for West Eurasian Europe [4, 5]. populations (Table 2). Haplogroup H has a sister haplogroup V. As Specific mtDNA types have already been estab- assumed from its geographic frequency distribution lished for most race groups in the early 1990s [2, 4]. and genetic diversity, haplogroup V arose in South- More than 80% mtDNA types of the West Eurasian western Europe about 16,000 years ago and spread populations belong to haplogroups H, I, J, T, U, V, W, throughout Europe in the postglacial period [16]. We and X, which are considered originating from the observed mtDNA types of this haplogroup in Bash- Upper Paleolithic European gene pool. According to kirs, Tatars, Chuvash, Mordvinians, and Mari (Table published data, the population frequency of haplo- 2). Although its frequency was relatively high (about group H is maximal (40Ð50%) in Western and North- 11%) in the European Mari population, haplogroup V ern Europe; intermediate (20Ð40%) in Southern, was represented by only one mtDNA type (a substitu- Southwestern, and Eastern Europe, Northern Africa, tion in position 16,298), suggesting a recent founder and Turkey; and low (less than 20%) in the Middle effect. East, India, and Central [6]. This haplogroup is thought to originate in the Middle East [15]. Cluster U was the second frequent in the VolgaÐ Ural populations (Table 2). This cluster is considered Haplogroup H was among the most common hap- as one of the most ancient clusters, its evolutionary logroups of most VolgaÐUral populations (Table 2). age being estimated at 50,000 years [5, 7]. Cluster U The frequency of this haplogroup was maximal in includes several subclusters (U1ÐU8), each having a Mordvinians (about 42%) and Mari (about 40%) and specific geographic distribution. Thus only haplo- lowest (about 12%) in Bashkirs. The diversity of the groups U1ÐU5 have been found in West European mtDNA variants of haplogroup H is shown in Fig. 3. populations. Subcluster U6 has been observed in

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Africa, while U7 is typical in the populations of Jor- Table 1. Haplogroup-determining mutations in mtDNA HVSI dan, Kuwait, , and Saudi Arabia. In addition, clus- ter U includes haplogroup K [4]. Cluster HVSI motif Haplogroups U5 and U4 were the most common in HV the VolgaÐUral region. The former is prevalent H (53.0%) in Saami and is also present in other North V 16,298 European populations [17Ð20]. In our sample, haplo- group U5 was not only observed in the Finno-Ugric K 16,224Ð16,311 populations, it also occurred at a high frequency in U1 16,249 Bashkirs, Tatars, and Chuvash. As Fig. 4 shows, hap- U2 16,051Ð(16,129CÐ16,189) logroup U5 had several founder types. One of these, U3 16,343 so-called Saami motif (16,144Ð16,189Ð16,270) has U4 16,356 earlier been detected in Saami (37%), Finns (2%), and the Karelian population (6%) [20]. We found this U5 16,270 motif in Mari, Mordvinians, and Bashkirs. U8 16,342 Of all cluster U haplogroups, U4 was the most J 16,069Ð16,126 common in Trans-Ural Bashkirs and Komi-Zyryans T 16,126Ð16,294 (16 and 24%, respectively). While haplogroup U5 is I 16,129Ð16,223Ð16,391 common in Western Europe and Mediterranean coun- tries and occurs also in the Middle East and Central W 16,223Ð16,292 Asia, haplogroup U4 is characteristic of the northeast- N1a 16,147AÐ16,223 ern populations of Western Europe. Haplogroup U4 N1b 16,145Ð16,176GÐ16,223Ð16,390 was observed at a low frequency in Mordvinians (2%) N9 16,257AÐ16,223Ð16,261 and Udmurts (4%). We detected several founder vari- B 16,189 ants with substitutions in positions 16,356, 16,356Ð 16,261, 16,356Ð16,362Ð16,242AÐ16,288, and Y 16,126Ð16,231Ð16,266 16,356Ð16,134. Subcluster U4a (16,356Ð16,134) had F 16,304 a distinct stellate phylogenetic tree. The period of its A 16,223Ð16,290Ð16,319Ð16,362 divergence in the VolgaÐUral region was estimated at M 16,223 17,800 ± 2900 years (ρ = 0.88). C 16,223Ð16,298Ð16,327 The populations of the VolgaÐUral region proved Z 16,129Ð16,185Ð16,223Ð(16,224)Ð16,260Ð16,298 to be heterogeneous with respect to haplogroup U2. This haplogroup is known to include two major vari- D 16,223Ð16,362 ants. One (HVSI motif 16,051G, 16,129C, 16,189C) G 16,223Ð16,362 is specific for Europe, whereas the other is restricted to India [21]. European U2 lines were found in Bash- kirs, Tatars, Mordvinians, and Udmurts. higher in the Finno-Ugric populations and maximal Haplogroup U3 is rare in Europe [5] and absent (24%) in Udmurts. The phylogenetic tree of this hap- from [22]. A high genetic diversity of this logroup was rather complex (Fig. 5), including several haplogroup has been observed in the Caucasus (Ose- major variants (16,126Ð16,294, 16,126Ð16,294Ð tia, Georgia, Armenia) and in Turkey [4, 23]. In our 16,296Ð16,304) and subcluster T1 (16,126Ð16,294Ð sample, Tatars and Chuvash had two variants, which 16,163Ð16,186Ð16,189). have earlier been detected in Turks, Armenians, and Haplogroup J includes several founder types in Nogaians [23]. Europe [24]. Variants of this haplogroup were Variants of haplogroup U8 were rarely observed in observed at a frequency of 2Ð10% in all ethnic groups Gaininsk Bashkirs, Komi-Zyryans, and Chuvash. examined. The phylogenetic tree of this haplogroup is shown in Fig. 5. The distribution of haplogroup K in the popula- tions of the VolgaÐUral region is also interesting Haplogroup I occurs predominantly in Northwest- (Table 2). This haplogroup, which includes several ern Europe [5]. Its distribution in the populations of mtDNA variants, was relatively frequent in the Turkic the VolgaÐUral region was nonuniform. A single ethnic groups and was rarely, if at all, observed in the mtDNA variant of haplogroup I was relatively fre- Finno-Ugrian populations. quent (6%) in Mordvinians. A similar variant was observed in Bashkirs, Tatars, and Chuvash, but not in Haplogroups T and J originate from the Middle Mari, Udmurts, and Komi-Zyryans (Fig. 5). East [5, 7]. The former accounts for about 8% mtDNA lineages in Europe and includes two subclusters [5, The mitochondrial gene pool of the East Eurasian 24]. In our sample, the frequency of haplogroup T was population includes haplogroups M, A, F, B, and Y.

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pre-V NlaIII 298 4577 00073 HV 00072 V R MseI 126 14766 5B 4C 15M 4T 2O 311 pre-HV O B 2M T T 153 O í 217 2O T 129 319 223 183 82 169 Ç í 184A M 2í AluI í 7025 í B

93 ä H ë 240 ëä

Çí 4 P 2K í 316 T 222 ä 362 265 265 O 325 140 O ä O O O í 92 114 300 2í í 265T 278 240C 294 136 272 246 í 293 192 O 3T 2U é T 2O 3K 5P 3B P 3C B 8T 8M O U T 2U 7M 295 129 93 217

362 ë U 311 B 318 368 í 2B 2K 193 294 T M 355 í 304 2T M 354 P 3O 124 14O 25T 9U 28M 9P ë 296 í C 2M 2O 189 2BA 2P 2T 3C 9B 8K 80 261 C B 4T B 319 3M 2O í 356 í 299 80 327 274 325 é í 240 2O 274T 126 61 221 í é 69 111 00073G 249 K 4M U 311 362 é 111G 114A 193 B 192 ë 162 é 259 168 136 K B 278 190A 2B P 234 ë 2O B O í T O B C M 83 2U 344 é 304 51 2B í 311 209 í 266 P é ë 4U

Fig. 3. Median network of haplogroup H in ethnic groups of the VolgaÐUral region. Here and in Figs. 4–6: Circle size reflects the haplotype frequency. Mutations in HVSI were identified against the Cambridge reference sequence [13]. Their positions are indi- cated as the actual position minus 16,000; i.e., 233 corresponds to position 16,233. The ethnic groups were (T) Tatars, (C) Chuvash, (M) Mari, (O) Mordvinians, (K) Komi-Zyryans, (P) Komi-Permyaks, and (U) Udmurts.

Supercluster M and its derivatives C, D, G, and Z haplogroup M is rare, occurring at a frequency of less account for about 50% mtDNA lineages of East Eur- than 2%. By and large, haplogroups of the European asian ethnic groups. In Western and Central Europe, and Asian populations do not mix together, having an

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T

M O C O C 2T T 256 C 5B 311 2M T 189 93 234 C 93 390 T 129 O O T 261 215 311 2T 76 284 8M 4T 136 T B C 6M 294 P 2C 2T 114A B 129 291 234 311 B 362 O 304 U T 362 192 134 311 C O 264 304 5M B 2M 3B 2B T 2B 2O 4K C 9B 2O 3T 113C 184 6B C 7T 311 356 154 B 8U 2K M 2P 2K 144 362 B 5O 134 147 258 319 2O 356 4B 5C 2T B T 256 145 261 362 129 189 T 311 4M O 2K K T 93 192 129 221 2B 93 C O 3B P 270 U4 K 4M 186 2T P 7K 3B P P U5 283 3T 242A 217 93 2T P 235 311 234 3B K U8 356 P U1 K 288 K P 2T 111 146 224 U2 B 355 187 214A 51 342 311 2C U 249 2B 4T C B T K 2P 327 U3 3Ç 6T 2T 129C 2C M 189 343 368 B C M T 86 189 3T 93 T 294 362 256 189 P M 311 O 390 2T 168 O 92 T 2O 260 258 261 291 2T T 234 362 K 356 153 O 362 261 248 173 2O T 5U C 311 260

C 365 362

T 5U

Fig. 4. Median network of haplogroup U in ethnic groups of the VolgaÐUral region. overlap of no more than 5%. The only exception is the The distribution of East Eurasian haplogroups (A, Central Asian contact region with mtDNA lineages B, Y, F, M, C, Z, D, G) substantially varied in the eth- that are characteristic of both Western and Eastern nic populations under study (Fig. 6). The frequency of Eurasia. Asian mtDNA variants was lower in the Finno-Ugric

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3P T 272 3B 242 189 I 6U T O C 319 B 2O N1a 172 O 2P 391 T 86 355 311 278 320 172 4T 248 147A 129 B W 325 192 K N1b DdeI 3T B O 4T 10394 292 P 305 390 176G HaeIII P T 284 273 U 145 8994 R2 B B 93 162 239 216C 146 T N1 U 311 O 4T 3M B P P 241C 126 K 4O 189 T DdeI T 171 1715 6U T O T U 2T 93 236 P 136184 T M 78 T T N 222 260 2U 172 209 O 230 172 93 O L3 189 223 T 7B T 2U 71 172 U 301 296 MboII 231 37 296 304 292 12704 J T T 2U 324 2B U B U 325 T 2P U R 261 T 4K 192 T HV 290 291 93 186 NlaIII 245 294 4216 145 189 319 209 243 B T 311 BamHI 172 177 163 13366 126 B T T 148 B 4P 2K B 3U BstOI 69 362 13704 8M 9T 3O 2M 5T 2C 11U 2B 2C 2P 6K 193 187 T 278 2M 2O U 324 C O 92 189 189 390 294 352 T 126 U 366 M U T O O M

Fig. 5. Median network of several West Eurasian haplogroups in ethnic groups of the VolgaÐUral region. ethnic groups and maximal in Bashkirs (Table 2). Bashkirs. Only one variant, 16,223Ð16,298Ð16,327 Bashkirs displayed a higher frequency (42%) and mapping to the center of the phylogenetic tree, was higher genetic diversity of Mongoloid mtDNA vari- found in Udmurts, Tatars, Bashkirs, Chuvash, and ants as compared with Tatars (12%), who live in the Komi-Permyaks. neighboring region, and with Chuvash (9%), who live to the west of Bashkirs and belong to the same lan- Since the frequency of Asian haplogroups is no guage group. more than 2% in Balto-Finnish populations (Estonia, Haplogroups C and Z have a common origin and Finland) [20, 27], we think that the distribution of are widespread in Asian populations and especially in mtDNA variants in the ethnoses of the VolgaÐUral the indigenous population of Northern and Eastern region mostly depends on geographic distances rather Siberia. The frequency of haplogroup C reaches 50% than on linguistic barriers. In other words, the Finno- in and Yukagirs, is about 30% in North Siberian Ugric populations of the region are more similar to ethnic groups, and gradually decreases to no more their Turkic geographic neighbors than to the linguis- than 10% in Chukcha, , and Itelmen to the tically related Balto-Finnish populations. east, in and to the south, and in Selkups and Kets to the west [25, 26]. In Southern and The frequency of East Eurasian mtDNA variants Western Europe, haplogroup C occurs at a frequency was 21% in Udmurts, who belong to the Perm branch of no more than 1%, if at all. Similar data were of the Finno-Ugric language family. Haplogroups Z obtained for the Finno-Ugric populations of the (5%) and D (12%) were most common, each being VolgaÐUral region: the frequency of haplogroup C represented by a limited number of variants (Fig. 6). was 0% in Komi-Zyryans and less than 3% in Aside from Udmurts, haplogroup Z was found in four Udmurts. The only exception was the Komi-Permyak Mari, two Bashkirs, one Tatar, and one Komi-Zyryan. population with the frequency reaching 8%. The high- This haplogroup is characteristic of Tungus-Manchu- est (12%) frequency of haplogroup C was observed in rian populations of Northern Siberia [29], and is

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O B 278 G 265C 2P K B 4U 293C B B 294 266 D Z 274 309 262 3B 290 8U 2U 2T 2B 4B 169 M 235 93 2B 129 243 196 3B 234 189 3U 4M 239 T K 2B 3B T 390 173 344 164 227 274 T 260 319 92 111 B 3B B 2T B 156 4B 311 224 B 171 278 P 2T 362 3U M 189 290 C 239 U 185 189 C 3B 129 B 256 B B AluI B 325 129 129 HaeII 93 357 311 5176 4830 258 274 184 294 245 P B AluI U 13262 311 2U 327 M B 286 4T 3B 362 C 3B T C 4P 298 C T B 287 147 126 2O B M B 129 298 297 266 Y 93 2B B 391 T DdeI 231 4B 192 10394 93 B T T 223 T N9 M7b 172 L3 126 261 MnlI 257A 129 10871 291 TasI 3B 5416 2B 2P N HaeIII 663 311 280 II F 189 172 T Mbo 2B 290 12704 232A 293C B 304 319 129 221 242 223 249 358 249del 227C 311 230 R 2C B 172 4T M 67 362 227 B 293 172 360 317T 2B –9bp 162 M 4B 311 8B 189 189 B B A T U K P 243 F1a F1b 274 B 2B

Fig. 6. Median network of East Eurasian haplogroups in ethnic groups of the VolgaÐUral region. present in Mongols [28], Turkic populations of Cen- European populations and far rarer in the ethnic tral Asia [22], and, interestingly, in Saami [18, 20]. groups of the VolgaÐUral region. Likewise, a low genetic diversity of Udmurts has been inferred from It should be noted that Udmurts had a lower the data on Y-chromosomal polymorphisms (diallelic mtDNA diversity and relatively high frequencies of loci, STR) [30]. These findings suggest the founder haplogroups U2 and T, which are characteristic of effect and gene drift for the ethnic history of Udmurts.

MOLECULAR BIOLOGY Vol. 36 No. 6 2002 810 BERMISHEVA et al. % n % n % n % n % = 979) of the VolgaÐUral region n N % n % n % Bashkirs Tatars Chuvash Mordvinians Komi-Permyaks Komi-Zyryans Mari Udmurts n Frequency distribution of mtDNA haplogroups in the populations ( Haplogroup HpV, VpHV, HVUKU* 0U1 1 27 7 00U2 0 12.2 0U3 0.5 3.2 00 0 0U4 63 20.90 70 00U5 2 9 3 28.5 00 U8 0 30.7J 0.9 3.9 1.4 67T 15 0 1T1 0 29.4 0 4 13 28 27.3I 0.5 0 30W 5 24 0 12.7 5.7 00 0 7.3 43N1a 0 1 13.6 2 0 43.6N1b 00 2.2 0 16 42.2 4 0 7R 41.80 5 0.5 5 12 24 0.9 00 1 27M 1 24 9 7.0 00 7.3 3.2M* 10.5 2.2 4.9 5.4 26.5 0 0 1.0 3C 32.4 4.1 9 1.8 1 17 8Z 8 1 0 0 13 21 0 0 21 0 1.4D 16.4 0.5 6 2 7.5 3.6 14.5G 17.6 0 9.2 1.8 0 33.9 0N9 0 1 61 2 2.6 2 2.0 3 7 4 23 16Y 3 2 1 55 0 0 1 27.6 0F 0 0 0.9 26 1.8 15.7 0 37.1 2 2.0 1 6.9 1.8 0B 00 5.5 1.4 40.4 0.4 0 3.6 0 20 0 2 11.8A 1.4 0 1 00 20 0 4 36 1 7 0 0 0 0 0 0 0 3.6Others 1.4 0 22 1 0 10 0 8 5 8.8 0.9 10.500 0 8Sample size 1 00 26.5 9.0 0 4 0 3 00 146.300 1.8 0.4 21.8 0 5.4 0 9.5 15 0 0 00 0 4.5 00 0 2 7.8 2.2 1.8 4 20.900 2 7.9 0 1 25 1.8 1.4 00 0 1.6 0 11.0 6 0 15 6 221 6 2.0 00 0 0 3 1 0 4 10 24.8 1.5 0 7.3 0 0.4 1 3 00 24.2 2.6 2 8 3 5.9 0 0 9.7 0 5 13.5 1.8 0 4.1 1.8 0 0 0 0 0 1.4 0 3 14 1.8 2 0.9 3.6 2.2 2 0 19 228 8 0 0 6.8 6 1 10.3 0 0 1 0 2.9 0 7 1 0 0 14.0 3.6 0 2 7 0 2.7 12.9 2 1.0 0 9.7 0 12 4 0 0.4 1.6 9.5 0 2.0 0 0 3.1 0 9 0 2 1 0 7 2 16.2 3.2 55 10 4.0 0 0 0 0 0 6 0 1 8.9 2.0 1.0 0 10 1 0 5.1 0 2 7.4 2.7 2 0 0 0 0 0 8.1 4 1.8 9.9 0 24 1.6 0 0 0 3.2 1.5 2 1 102 0 23.8 0 2 5.4 0 0 0 0 0 0 0 15 2.0 0 0.7 0 8 0 0 0 2.7 0 0 14.9 0 0 0 5.9 0 1 0 0 74 1 0 1 0 1 20 0 1 0 0 1.6 0 0 1.6 19.8 0.7 1.4 0.7 2 0 0 0 4 0 7 62 0 1 1.5 3 0 0 2.9 6.9 0 0 3.0 12 1.6 0 5 0 11.9 0 136 2 0 5.0 0 1.5 0 0 0 0 1 101 0 1.0 Table 2.

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Haplogroup M was well represented in all three and F in several Turkic (Bashkirs) and Finno-Ugric ethnographic groups of Bashkirs. Its frequency was (Udmurts, Komi-Permyaks) ethnic groups suggest a 28% on average, suggesting a substantial role of the substantial role of the Siberian and Central Asian Asian component for the Bashkir ethnogenesis. This components for the ethnogenesis of the VolgaÐUral is consistent with the early ethnic history of Bashkirs, populations. Mordvinians, Komi-Zyryans, and Mari since the ethnos is believed to originate from Turkic had low (3, 3, and 6%, respectively) frequencies of tribal confederations of the Altai, where ancient Bash- East Eurasian variants. Thus, the frequency and diver- kir and Mongolian tribes mixed together [12]. sity of Siberian and Central Asian mtDNA types sub- stantially increase in ethnic groups living at the Haplogroup A occurs at the highest frequency in boundary between Europe and Asia. It should also be Siberian populations and rarely, if at all, in the indig- noted that linguistically related populations geneti- enous populations of Southeastern Asia [2]. Thus the cally differ from each other. frequency of this haplogroup in Chukcha and Eskimo is 80%, higher than in all other world populations examined [25, 26]. We observed several variants of REFERENCES haplogroup A in Trans-Ural Bashkirs (6%); one of 1. Cann, R., Stoneking, M., and Wilson, A., Nature, 1987, these was also found in Chuvash, Tatars, and Mari. vol. 325, pp. 31Ð36. Haplogroups B and Y were detected only in Bash- 2. Wallace, D.C., Brown, M.D., and Lott, M.T., Gene, kirs. The former has been observed in , Tuvin- 1999, vol. 238, pp. 211Ð230. ians, and Altaians of Southern Siberia, and occurs at a 3. Denaro, M., Blanc, H., Johnson, M.J., et al., Proc. Natl. high (48%) frequency in Mongolia [28]. The common Acad. Sci. USA, 1981, vol. 78, pp. 5768Ð5772. ancestor of these ethnic groups has been assumed to provide haplogroup B to native Americans. We 4. Macaulay, V., Richards, M., Hickey, E., et al., Am. J. Hum. Genet., 1999, vol. 58, pp. 1309Ð1322. observed the variants of this haplogroup at the eastern boundary of Europe (Table 2). 5. Richards, M., Macaulay, V., and Bandelt, H.J., Ann. Hum. Genet., 1998, vol. 62, pp. 241Ð260. Haplogroup Y has first been identified in Eastern 6. Torroni, A., Huoponen, K., Francalacci, P., et al., Genet- Asia [25]. This haplogroup is absent from most Sibe- ics, 1996, vol. 144, pp. 1835Ð1850. rian populations, and occur at a high frequency in the populations of Kamchatka, , and Korea. Pre- 7. Richards, M., Corte-Real, H., et al., Am. J. Hum. Genet., sumably, haplogroup Y arose in ethnic groups of the 1996, vol. 59, pp. 185Ð203. Amur river basin [25] and was spread westwards by 8. Torroni, A., Lott, M., Cabell, M., et al., Am. J. Hum. ethnic groups of the Altaian language family [22]. Genet., 1994, vol. 55, pp. 760Ð776. This family includes Bashkirs, who had one variant 9. Torroni, A., Schurr, T., Yang, C., et al., Genetics, 1992, (16,126Ð16,231Ð16,266) of this haplogroup. vol. 130, pp. 153Ð162. An interesting distribution of haplogroup F (6%) 10. Torroni, A., Schurr, T., Cabell, M., et al., Am. J. Hum. was observed in Bashkirs. Variants of this cluster Genet., 1993, vol. 53, pp. 563Ð590. (subgroup F1b) showed a high frequency and low 11. Cavalli-Sforza, L., Menozzi, P., and Piazza, A., The His- diversity in Gaininsk Bashkirs (Fig. 6). Possibly, eth- tory and Geography of Human Genes, Princeton: Princ- nogenesis of this group of Bashkirs was substantially eton Univ. Press, 1994. affected by migrants from Central Asia, because sim- 12. Kuzeev, R.G., Narody srednego Povolzh’ya i Yuzhnogo ilar mtDNA variants have earlier been observed in Urala (Ethnic Groups of the Central Volga Region and Kazakhs, Uigurs, and Mongols [22, 28]. In addition, Southern Urals), Moscow: Nauka, 1992. our finding suggest a long-term isolation of this Bash- 13. Anderson, S., Bankier, A.T., Barrell, B.G., et al., Nature, kir group from its nearest neighbors, since haplogroup 1981, vol. 290, pp. 457Ð465. F was not found in any other ethnic group of the 14. Nei, M., Molecular Evolutionary Genetics, New York: VolgaÐUral region. Columbia Univ. Press, 1988. Cluster analysis showed that most mtDNA variants 15. Richards, M., Macaulay, V., Hickey, E., et al., Am. J. found in the ethnic groups of the VolgaÐUral region Hum. Genet., 2000, vol. 67, pp. 1251Ð1276. represent haplogroups characteristic of Western Eur- 16. Torroni, A., Bandelt, H.J., Macaulay, V., et al., Am. J. asia, testifying to a common origin of mtDNA lin- Hum. Genet., 2001, vol. 69, pp. 844Ð852. eages of West and East European populations. In our sample, the highest frequency of European mtDNA 17. Lahermo, P., Sajantila, A., Sistonen, P., et al., Am. J. types was observed in Mordvinians, Mari, and Komi- Hum. Genet., 1996, vol. 58, pp. 1309Ð1322. Zyryans. On the other hand, the frequencies of the 18. Lahermo, P., Sajantila, A., Sistonen, P., et al., Am. J. East Eurasian mtDNA variants were also high in the Hum. Genet., 1999, vol. 64, pp. 232Ð249. VolgaÐUral region in contrast to Western and Central 19. Sajantila, A., Lahermo, P., Anttinen, T., et al., Genome Europe. High frequencies of haplogroups G, D, C, Z, Res., 1995, vol. 5, pp. 42Ð52.

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20. Meinilä, M., Finillä, S., and Majamaa, K., Hum. Hered., 26. Starikovskaya, Y., Sukernik, R., Schurr, T., et al., Am. J. 2001, vol. 52, pp. 160Ð170. Hum. Genet., 1998, vol. 63, pp. 1473Ð1491. 21. Kivisild, T., Kaldma, K., Metspalu, M., et al., in 27. Villems, R., Adojaan, M., Kivisild, T., et al., The Roots Genomic Diversity, Kluwer Academic, 1999, pp. 135Ð of Peoples and Languages of Northern Eurasia, vol. 1, 152. Wiik, K. and Julku, K., Eds., Turku: Societas Historiae Fenno-Ugricae, 1998. 22. Comas, D., Calafell, F., Mateu, E., et al., Am. J. Hum. Genet., 1998, vol. 63, pp. 1824Ð1838. 28. Kolman, C. and Sambuughin, N., Genetics, 1996, vol. 142, pp. 1321Ð1334. 23. Metspalu, E., Kivisild, T., Kaldma, K., et al., in Genomic 29. Torroni, A., Sukernik, R.I., Schurr, T.G., et al., Am. J. Diversity, Kluwer Academic, 1999, pp. 121Ð134. Hum. Genet., 1993, vol. 53, pp. 591Ð608. 24. Finillä, S. and Majamaa, K., J. Hum. Genet., 2001, 30. Bermisheva, M.A., Viktorova, T.V., and Khusnutdi- vol. 46, pp. 64Ð69. nova, E.K., Genetika, 2001, vol. 37, pp. 1002Ð1007. 25. Schurr, T., Sukernik, R., Starikovskaya, Y., et al., Am. J. 31. Derenko, M., Malyarchuk, B., Dambueva, I., et al., Phys. Anthropol., 1999, vol. 108, pp. 1Ð39. Hum. Biol., 2000, vol. 72, pp. 945Ð973.

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