Fedorova 2003 Analysis of Mtdna Lineages in Yakuts.Molbiol

Home , Haplogroup A (mtDNA), Haplogroup C (mtDNA), Haplogroup D (mtDNA), Haplogroup F (mtDNA), Haplogroup G (mtDNA), Yakuts

Molecular Biology, Vol. 37, No. 4, 2003, pp. 544Ð553. Translated from Molekulyarnaya Biologiya, Vol. 37, No. 4, 2003, pp. 643Ð653. Original Russian Text Copyright © 2003 by Fedorova, Bermisheva, Villems, Maksimova, Khusnutdinova.

GENOMICS. TRANSCRIPTOMICS. PROTEOMICS UDC 575.174.599.9:943.87 Analysis of Mitochondrial DNA Lineages in Yakuts S. A. Fedorova1, M. A. Bermisheva2, R. Villems3, N. R. Maksimova1, and E. K. Khusnutdinova2 1Yakut Research Center, Russian Academy of Medical Sciences and Government of the Sakha Republic (Yakutia), Yakutsk, 677019 Russia; E-mail: [email protected] 2Institute of Biochemistry and Genetics, Ufa Research Center, Russian Academy of Sciences, Ufa, 540054 Russia 3Estonian Biocentre, Tartu, 51010 Estonia Received January 27, 2003

Abstract—To study the mitochondrial gene pool structure in Yakuts, polymorphism of mtDNA hypervariable segment I (16,024Ð16,390) was analyzed in 191 people sampled from the indigenous population of the Sakha Republic. In total, 67 haplotypes of 14 haplogroups were detected. Most (91.6%) haplotypes belonged to haplogroups A, B, C, D, F, G, M*, and Y, which are speciﬁc for East Eurasian ethnic groups; 8.4% haplotypes represented Caucasian haplogroups H, HV1, J, T, U, and W. A high frequency of mtDNA types belonging to Asian supercluster M was peculiar for Yakuts: mtDNA types belonging to haplogroup C, D, or G and undifferentiated mtDNA types of haplogroup M (M*) accounted for 81% of all haplotypes. The highest diversity was observed for haplogroups C and D, which comprised respectively 22 (44%) and 18 (30%) haplotypes. Yakuts showed the lowest genetic diversity (H = 0.964) among all Turkic ethnic groups. Phylogenetic analysis testiﬁed to common genetic substrate of Yakuts, Mongols, and Central Asian (Kazakh, Kyrgyz, Uighur) populations. Yakuts proved to share 21 (55.5%) mtDNA haplotypes with the Central Asian ethnic groups and Mongols. Comparisons with modern Paleoasian populations (Chukcha, Itelmen, Koryaks) revealed three (8.9%) haplotypes common for Yakuts and Koryaks. The results of mtDNA analysis disagree with the hypothesis of an appreciable Paleoasian contribution to the modern Yakut gene pool.

Key words: mitochondrial DNA, Yakut gene pool, haplotypes, median networks, phylogenetic analysis

INTRODUCTION Yakuts with Central Asian ethnic groups, Mongols, and Paleoasian indigenous populations. The molecular genetic approach is of importance for studying the evolutionary history of human populations and for estimating the contribution of individ- EXPERIMENTAL ual ethnic components to the gene pools of modern ethnic groups. Mitochondrial DNA is among the most Subjects. We tested DNA specimens of 191 Yakuts informative genetic systems suitable for characteriz- from the indigenous population of the Sakha Republic ing the structure of a gene pool. Owing to the maternal (Yakutia). The specimens were obtained from the inheritance, absence of recombination, and mutation DNA bank (Department of Molecular Genetics, Yakut rate higher than in nuclear DNA, mtDNA may be used Research Center), which contained the material col- as a major subject to study the origin of modern ethnic lected from 2001 to 2002 in the course of routine med- groups [1]. In the 1990s, extensive population-genetic ical examination or sampled at the Blood Transfusion studies have made it possible to identify and to clas- Department, National Medical Center of the Sakha sify the mtDNA types specific for individual races or Republic. Blood was obtained from adults who filled populations [1Ð3], as well as to trace the major human a questionnaire and gave their informed consent to migrations leading to colonization of Europe and participation in the study. The sample included unre- America. Yet the origin of most individual ethnic lated subjects; the ethnicity was recorded for three groups, including Yakuts, is still poorly understood. Only generations of maternal lineage. two publications on Yakuts are available: Derenko and Genomic DNA was isolated from peripheral blood Shields [4, 5] have analyzed the mtDNA nucleotide lymphocytes by proteinase K treatment and subse- diversity with a small sample of 22 individuals. quent phenolÐchloroform extraction [6]. In this work, we for the first time used a vast mate- A fragment of the mtDNA control region con- rial to characterize the Yakut mitochondrial gene pool. taining the hypervariable segment I (HVSI) was The mtDNA haplotypes were phylogenetically ana- amplified and purified with an ExoSAP-IT kit lyzed in order to elucidate the genetic relationships of (Applied Biosystems). HVSI (16,024Ð16,390) was

ANALYSIS OF MITOCHONDRIAL DNA LINEAGES IN YAKUTS 545

N = 2 N = 1

N = 1

N = 1 N = 1 N = 1 N = 2 N = 1

N = 2 N = 4 N = 7 N = 6 N = 2 N = 1 N = 51 N = 8 N = 2 N = 2 N = 26 N = 3 N = 1 N = 5 N = 19 N = 29 N = 10 N = 4

Yakutia

Fig. 1. Administrative map of the Sakha Republic (Yakutia). The number of specimens collected is indicated for each corresponding district (ulus). sequenced with a DYEnamic ET terminator cycle RESULTS AND DISCUSSION sequencing premix kit (Amersham Pharmacia Bio- Our sample included 191 Yakuts from various dis- tech) in an ABI 377 DNA Sequencer. Nucleotide tricts (uluses) of the Sakha Republic (Fig. 1). Analysis sequence alignment and analysis employed the Wiskon- of the 367-bp HVSI (16,024Ð16,390) revealed 67 hap- sin software package. lotypes with 65 variable nucleotide positions (Table 1). Haplogroups were identified against the Cam- The mtDNA haplotypes were classified; the assignment to a particular haplogroup was verified by bridge reference sequence [7, 8] and verified by RFLP RFLP analysis of 13 polymorphic sites of the mtDNA analysis of 13 restriction sites in the mtDNA coding coding region and analysis of deletion of region V region. located between the COII and tRNALys genes. The mtDNA haplotypes of Yakuts proved to belong to Median networks were constructed from the data 14 haplogroups. A median network of mtDNA haplo- on RFLPs and HVSI polymorphisms according to the types is shown in Fig. 2. median-joining algorithm [9]. An advantage of this method is that several equally possible phylogenetic The vast majority (91.6%) of the Yakut mtDNA haplotypes belonged to haplogroups specific for East trees are simultaneously present in one scheme. Eurasian ethnic groups. Asian mtDNA haplotypes Genetic diversity of mtDNA types was obtained as represented haplogroups A, B, C, D, F, G, M*, and Y. Peculiar of Yakuts, a high frequency was observed for mtDNA haplotypes representing Asian superclus- ()2 () H = 1 Ð ∑xi NNÐ 1 , ter M: in total, mtDNA types belonging to haplogroup C, D, or G and nondifferentiated mtDNA types of hap- where xi is the population frequency of a particular logroup M (M*) accounted for 81% of all haplotypes. mtDNA haplotype and N is the sample size [10]. The greatest diversity was characteristic of haplo-

MOLECULAR BIOLOGY Vol. 37 No. 4 2003

546 FEDOROVA et al.

Table 1. Diversity of mtDNA HVSI haplotypes in Yakuts (n = 191) Haplotype Haplogroup Haplogroup RFLP site no. Haplotype* n frequency frequency A HaeIII663+ 1 223, 242, 290, 319 1 0.0052 0.0209 2 39, 189, 223, 290, 319, 356, 362 1 0.0052 3 179, 223, 290, 311, 319, 362 1 0.0052 4 179, 223, 260, 290, 311, 319, 362 1 0.0052 B 9-bp deletion 5 86, 136, 189, 217 1 0.0052 0.0052 C AluI13262+ 6 129, 223, 235, 298, 327 1 0.0052 0.4398 7 129, 150, 223, 298, 327 2 0.0105 8 129, 223, 298, 327 6 0.0314 9 129, 223, 327 1 0.0052 10 148, 164, 223, 288, 298, 327 9 0.0471 11 148, 223, 288, 298, 327 2 0.0105 12 167, 171, 223, 298, 327, 344, 357 1 0.0052 13 171, 223, 256, 298, 327, 344, 357 1 0.0052 14 171, 223, 295, 298, 327, 344, 357 1 0.0052 15 171, 223, 298, 327, 344, 357 12 0.0628 16 189, 223, 298, 327 1 0.0052 17 223, 260.1A**, 294, 298, 327 1 0.0052 18 223, 260.1A**, 298, 327 3 0.0157 19 223, 298, 311, 327 8 0.0419 20 223, 298, 327 10 0.0524 21 223, 298, 327, 344, 357 1 0.0052 22 223, 291, 298, 327 1 0.0052 23 93, 129, 223, 298, 327 6 0.0314 24 93, 129, 223, 327 13 0.0681 25 93, 129, 223, 327, 335 1 0.0052 26 93, 214, 223, 261, 288, 298 1 0.0052 27 93, 223, 261, 288, 298 2 0.0105 D AluI5176Ð 28 129, 189, 223, 362 1 0.0052 0.3037 29 129, 223, 294, 362 1 0.0052 30 172, 189, 223, 266, 362 2 0.0105 31 180, 223, 294, 362 1 0.0052 32 223, 245, 362 2 0.0105 33 223, 291, 362 12 0.0628 34 223, 319, 320, 362 1 0.0052 35 223, 319, 362 4 0.0209 36 223, 362, 368 1 0.0052 37 42, 93, 214, 223, 362 1 0.0052 38 92, 129, 223, 271, 362 2 0.0105 39 92, 172, 189, 223, 266, 362 23 0.1204 40 92, 172, 189, 223, 362 2 0.0105 41 92, 172, 189, 223, 266, 305, 362 1 0.0052 42 93, 192, 223, 232, 362 1 0.0052 43 93, 223, 232, 261, 290, 362 1 0.0052 44 93, 223, 232, 290, 362 1 0.0052 45 93, 223, 232, 362 1 0.0052

MOLECULAR BIOLOGY Vol. 37 No. 4 2003

ANALYSIS OF MITOCHONDRIAL DNA LINEAGES IN YAKUTS 547

Table 1. (Contd.) Haplotype Haplogroup Haplogroup RFLP site no. Haplotype n frequency frequency F HincII12406Ð 46 189, 232ëA, 249, 304, 311 4 0.0209 0.0628 47 189, 232ëA, 304, 311 1 0.0052 48 92íA, 291, 304 3 0.0157 49 172, 189, 232ëA, 249, 304, 311 4 0.0209 G HaeII4830+ 50 223, 227, 278, 362 3 0.0157 0.0419 51 189, 223, 227, 234, 278, 362 2 0.0105 52 223, 227, 274, 278, 362 2 0.0105 53 223, 227, 234, 278, 362 1 0.0052 H AluI7025Ð 54 CRS 3 0.0157 0.0262 55 291 2 0.0105 HV1 Tru1I14766Ð 56 67, 260, 355 2 0.0105 0.0105 J MvaI13704Ð 57 69, 126 2 0.0105 0.0105 M AluI10397+ 58 145, 148, 188, 189, 223, 381 2 0.0105 0.0262 59 145, 148, 162, 188, 189, 223, 381 1 0.0052 60 93, 129, 223, 311 1 0.0052 61 145, 223, 295, 304 1 0.0052 T BamHI13366+ 62 126, 294, 296, 362 2 0.0105 0.0105 U HinfI12308+ 63 144, 189, 270 1 0.0052 0.0105 64 189, 356 1 0.0052 W HaeIII8994Ð 65 223, 292 3 0.0157 0.0157 Y MboI7933+ 66 126, 231, 266, 342 1 0.0052 0.0157 67 126, 231, 266 2 0.0105 Notes: * Haplotypes are described as HVSI nucleotides differing from those in the Cambridge reference sequence [7, 8]. Only the position is indicated in the case of transition; transversions are fully described. ** Single-nucleotide insertion is indicated. groups C and D, which comprised 22 (44%) and 18 found in North-East Asian ethnic groups of Kam- (30%) haplotypes, respectively. chatka (Koryaks, Itelmen) and the Chukotka Penin- sula (Chukcha, Eskimo) [13, 14]. In addition to Mongoloid mtDNA haplotypes, the Yakut gene pool included haplotypes of groups H, HV1, The gene pools of Turkic ethnic groups have a high J, T, U, and W, which are widespread in European and genetic diversity (H), which is maximal in Kazakhs Middle Eastern populations. In total, Caucasian mtDNA and Kyrgyz. Yakuts have the lowest genetic diversity haplotypes accounted for 8.4% of all haplotypes. among the Turkic populations. Small populations of Northeastern Asia have even a lower diversity, as char- For comparison, we used the published data on acteristic of ethnic groups originating from a small genetic diversity and frequencies of Caucasian and ancestral population and being to some extent isolated Mongoloid mtDNA haplotypes in Turkic ethnic for a prolonged period. groups, Mongols, and North-East Asian populations (Table 2). Generally, there is certainly a west-east We analyzed the frequencies of individual mtDNA cline in frequencies of race-speciﬁc haplotypes. The haplogroups in Yakuts; in Turkic ethnic groups of the highest (89%) frequency of the Caucasian component VolgaÐUral region, Central Asia, and the AltaiÐSayan has been observed in the gene pools of Chuvash and Highlands; in Mongols; and in the indigenous popula- Tatars, indigenous populations of the VolgaÐUral tions of Northeastern Asia (Table 3). region located at the boundary between Europe and The highest (44%) frequency in the Yakut mito- Asia [11]. The Mongoloid component increases up to chondrial gene pool was observed for haplogroup C, 68% (in Kyrgyz) in Central Asian ethnic groups which is widespread in Asian ethnic groups and espe- (Kazakhs, Kyrgyz, Uighurs) [12]. Only Mongoloid cially in the indigenous populations of Siberia. Fre- mtDNA haplotypes (frequency 100%) have been quency of this haplogroup is high in Evenks (84.3%)

MOLECULAR BIOLOGY Vol. 37 No. 4 2003

548 FEDOROVA et al.

93 2

335 266

298 23

214 6 2 235 2 93 327 2 G 150 189 92 93 2 261 6 2 93 3 234 274 9 164 172 2 148 129 260.1Ä 291 3 288 2 189 227 320 266 8 311 10 271 344 92 357 4 287278 167 171 327 189 C 319 12 129 180 368 295 M7c +AluI 13262 10 304 294 +HaeII 4830 145 –AluI5176– II 4830 256 Alu 93 292192 125129 298 291 245 232 295 290 93 368362 D 42 162 311 2 2 381 189 188 148 214 261 145 M 2 +AluI 10397 L3 2 242342 268266 231 Y +DdeI 10394 W 223 356 2 120126 189 292 N 39 86 +Mbo 7933 362 A4 –HaeIII 8994 290 319 179 B 136 +HaeIII 663 242 311 217 223 260 189 9 bp del R 3 249 del 92A + HI 13366 126 304 201291 2 362 296269 Bam 294 –Tru1I 14766 –HincII 12406 F2a T +Hinfl+Hinfl 12308 12308 –Mva–MvaII 13704I 13704 189 –AluI 7025 67 69 270 356 232A 3 355 311 2 F1b J 189 291 260 249 189 4 2 2 144 172 U4 H HV1 4 U5

Fig. 2. Phylogenetic tree of the mtDNA haplotypes observed in Yakuts. Haplotypes are shown with circles, with the number of car- riers indicated. Caucasian haplotypes are shown black. Here and in Fig. 3: Distinguishing nucleotide polymorphisms of HVSI or RFLPs of the coding region are indicated on the links.

[15], Tuvinians (48.9%) [16], Koryaks (36.1%) [13], Cluster D (30%) was the second most frequent and Khakassians (35.2%) [17], and falls to 10% or Asian haplogroup in Yakuts. Compared with haplo- lower in Chukcha and Eskimo in the east, Kazakhs group C, it has much the same distribution through and Uighurs in the south, or Tatars and Chuvash in the Asian populations, being widespread in the indige- west. Haplogroup C occurs rarely or sporadically in nous populations of Siberia and in Central Asian eth- South Asian populations, which has been explained by nic groups. Haplogroup D accounts for more than their recent migration from Central Asia [18]. one-fourth of the mtDNA haplotypes observed in

MOLECULAR BIOLOGY Vol. 37 No. 4 2003

ANALYSIS OF MITOCHONDRIAL DNA LINEAGES IN YAKUTS 549

Table 2. Diversity of mtDNA haplotypes and frequencies of race-specific mtDNA haplogroups in the gene pools of Turkic ethnic groups and North-East Asian indigenous populations

Total HVSI Gene pool component, % Population n H haplotypes Caucasian Mongoloid Unidentified Yakuts 191 67 0.964 8.4 91.6 0 Turkic ethnic groups Chuvash 55 39 0.988 89.1 9.1 1.8 Tatars 174 91 0.976 89.1 10.3 0.6 Bashkirs 211 105 0.988 60.7 39.3 0 Uighurs [12] 55 46 0.993 34.5 54.5 10.9 Kazakhs [12] 55 45 0.990 40.0 56.4 3.6 Kyrgyz [12] 95 70 0.990 27.4 68.4 4.2 Altai-kizhi [17] 92 nd nd 23.9 67.4 8.7 Shorians [17] 42 nd nd 35.7 64.3 0 Khakassians [17] 54 nd nd 18.5 75.9 5.6 Soyots [17] 34 nd nd 5.9 88.2 5.9 Tuvinians [21] 36 nd nd 5.6 94.4 0 North-East Asian populations Evens [4] 65 33 0.962 0 90.8 9.2 Koryaks [13] 147 41 0.945 0 100 0 Itelmen [13] 46 19 0.931 0 100 0 Chukcha [14] 65 19 0.883 0 100 0 Eskimo [14] 77 12 0.819 0 100 0 Mongolia Mongols [19] 103 83 0.990 13.6 86.4 0 Note: The number of HVSI haplotypes has not been determined (nd) in some cases, as mtDNA haplogroups have been established by RFLP analysis without HVSI sequencing.

Mongols [19]. The highest (up to 50%) frequency of Haplogroup F originates from South Asia and this haplogroup has been reported for Soyots [17]. occurs at a high frequency in Vietnamese (32%), Interestingly, Yakuts proved to have a high (12%) fre- Malays (28%), Koreans (15%), and in Chinese popu- quency of haplotype 16,092-16,172-16,189-16,223- lations [18]. Possibly, this haplogroup spread from 16,266-16,362, which belongs to subcluster D5a. This Southeastern to Central Asia. The HVSI motif 16,172- frequency was far greater than that of any other 16,304, which is characteristic of haplogroup F, has mtDNA haplotype in our sample. Subcluster D5a is been found in Mongols [19], Kazakhs, Kyrgyz, and speciﬁc for populations of North China and is Uighurs [12]. Yakuts (6.3%) also proved to possess the extremely rare in Central Asia or Siberia [20]. mtDNA haplotypes of this group. In the Yakut mitochondrial gene pool, haplogroup F is represented by Haplogroup A, which is common for virtually all two subclusters F1b and F2a. The former (Fig. 2) is Siberian ethnic groups examined, occurred at a fre- most common in Central Asia, Mongolia, Korea, and quency 2.1% in Yakuts. This haplogroup is the major Japan [20]. Subcluster F2a lacks speciﬁcity to a par- component of the mitochondrial gene pool in ticular geographic region and occurs at a low fre- Chukcha and Eskimo (68 and 77%, respectively) [14]. quency in numerous Asian populations. Haplogroup G contains two subclusters: G1, which South Asian haplogroup B, which is similar in dis- is characteristic of North-East Siberian populations tribution to haplogroup F, occurred at an extremely and occurs at the maximal frequency in Koryaks low (0.5%) frequency in Yakuts. (42%) and Itelmen (68%), and G2a, the highest (8.8%) frequency of which has been detected in Cen- A low (1.6%) frequency was also observed for hap- tral Asia [20]. In Yakuts, haplotypes of subcluster G2a logroup Y, which has recently been characterized [13] were found at a relatively low (4.2%) frequency. and is thought to originate from the Far East.

MOLECULAR BIOLOGY Vol. 37 No. 4 2003

550 FEDOROVA et al.

Table 3. Haplogroup frequency distribution in the gene pools of Turkic ethnic groups and North-East Asian indigenous populations Haplogroup frequency, % Population n A B C D G F M* J T U H Others Yakuts 191 2.1 0.5 44.0 30.4 4.2 6.3 2.6 1.1 1.1 1.1 2.6 4.0 Turkic ethnic groups Chuvash 55 1.8 0 1.8 3.6 0 0 1.8 5.5 3.7 36.4 25.5 19.9 Tatars 174 2.3 0 1.7 2.9 1.2 0 2.3 8.1 8.1 24.7 31.6 17.1 Bashkirs 211 4.3 0 12.8 8.1 4.7 6.2 1.0 3.3 5.2 27.5 14.2 12.7 Uighurs [12] 55 7.3 7.3 1.8 16.4 0 7.3 7.3 0 1.8 16.4 20.0 14.4 Kazakhs [12] 52 9.6 5.8 7.7 19.2 5.8 1.9 5.8 0 7.7 5.7 15.4 15.4 Kyrgyz [12] 92 3.3 6.5 14.1 19.6 7.6 3.3 6.5 5.4 3.3 3.3 18.5 8.6 Altai-kizhi [17] 92 3.3 3.3 30.4 9.8 4.4 5.4 9.8 5.4 0 5.4 5.4 17.4 Shorians [17] 42 0 2.4 7.1 9.5 0 43.0 2.4 11.9 0 0 21.4 2.3 Khakassians [17] 54 3.7 5.6 35.2 9.3 0 22.0 0 1.9 1.9 11.1 3.7 5.6 Soyots [17] 34 8.8 2.9 17.6 50.0 000005.9014.8 Tuvinians [21] 36 5.6 14.0 36.1 16.7 5.6 8.3 0 0 0 2.8 2.8 8.1 Tuvinians [16] 458 3.1 3.7 48.9 9.9 nd nd nd nd nd nd nd nd North-East Asian populations Koryaks [13] 155 5.2 0 36.1 1.3 41.9 0 0 0 0 0 0 15.5 Itelmen [13] 47 6.4 0 14.9 0 68.1 0 0 0 0 0 0 10.6 Chukcha [14] 66 68.2 0 10.6 12.1 9.1 0 0 0 0 0 0 0 Eskimo [14] 79 77.2 0 2.5 20.3 00000000 Evenks [15] 51 3.9 0 84.3 9.8 0 2.0 0 0 0 0 0 0 Evens [4] 65 4.6 0 26.2 15.4 0 1.5 0 0 0 0 0 52.3 Mongolia Mongols [19] 103 3.9 9.7 14.6 30.1 2.9 5.8 11.7 0 1.0 3.9 7.8 8.6 Note: Cases when a haplogroup has not been determined (nd) are indicated. Shaded are populations with mtDNA haplotypes established by a set of HVSI mutations without performing RFLP analysis.

A relatively broad spectrum of Caucasian haplo- To assess the genetic relationships of Yakuts with groups (H, HV1, J, T, U, W) was found in Yakuts. Yet Mongols and ethnic groups of Central Asia, we used these haplogroups each occurred at a low (1Ð2.6%) fre- phylogenetic analysis of their mtDNA haplotypes. A quency, which was maximal in the case of cluster H. phylogenetic tree of mtDNA types of Yakuts, Mon- gols, and the pooled Central Asian population (Kaza- Thus, the mitochondrial gene pool of Yakuts is khs, Kyrgyz, and Uighurs) is shown in Fig. 3a. diverse and has a highly speciﬁc haplogroup spec- Branches of the tree grow away from a trunk common trum. Its peculiar feature is a great prevalence of hap- for various Asian populations. Of all mtDNA haplo- logroups C and D (total frequency 74%). In mtDNA groups found in Yakuts, those occurring at a frequency haplotype frequencies, Yakuts strikingly differ from less than 2% are not indicated in Fig. 3. Haplogroup C the Turkic populations of the VolgaÐUral region, includes seven subclusters, which diverged from the major HVSI motif 16,223-16,298-16,327 as addi- Mongols, and the indigenous populations of Chukotka tional mutations accumulated in the course of evolu- and Kamchatka. In high frequency of haplogroup C, tion. Two of the subclusters proved to be speciﬁc for Yakuts are similar to Evens and Tuvinians; yet addi- Yakuts. Of these, one has insertion of A in position tional data on HVSI polymorphism are necessary for 16,260 and the other, transition in position 16,291. elucidating their phylogenetic relationships. The The other subclusters of haplogroup C are common mtDNA haplotypes characteristic of the populations for Yakuts, Mongols, and Central Asian ethnic groups. living to the south of Yakuts testify to the southern In haplogroup D, most mtDNA haplotypes observed contribution to the Yakut gene pool. in Yakuts cluster with those characteristic of Mongols

MOLECULAR BIOLOGY Vol. 37 No. 4 2003

ANALYSIS OF MITOCHONDRIAL DNA LINEAGES IN YAKUTS 551 ecting ﬂ 92 Yakuts Koryaks Itelmen Chukcha 266 264 366 214 180 290 92 42 192 271 356 232 172 172 260 162 266 39 129 245 93 294 173 179 320 249 93 189 189 265 381 245 292 319 176 311 111 D 93 192 368 129 342 311 189 207 85 5176 93 304 I 232A 311 362 293 188 93 129 hs, Kyrgyz, Uighurs) or (b) Yakuts, Uighurs) or (b) hs, Kyrgyz, 242 4830 Alu 265 119 II – 172 145 G 189 148 129 290 311 93 92A 93 406 69 Hae 319 2 + 278 1 261 295 291 273 145 311 207 II 227 362 172 291 290 asian ethnic groups), with the area re 362 311 262 A 234 –Hinc F 291 274 13 189 M I 298 265 C 304 663 327 352 Alu 93 III + R 260.A 10397 189 129 766 I 93 4 150 Hae 357 1 311 + Alu 288 I 93 223 124 + I10394 344 N 235 7025 223 298 –Tru1 93 Dde I 318 + 148 93 H 357 171 –Alu 261 335 164 93 L3 327 311 291 256 295 167 298 260 18 189 214 93 197 311 261 266 92 261 259 265 260 111 362 93 271 249 179 188 184 171 214 180 92 Yakuts Central Asian populations Mongols 290 164 42 256 111 192 290 271 179 356 172 294 232 228 172 209 86 266 223 164 39 311 92 249 104 256 294 129 93 220 283 311 145 295 278 249 129 320 335 254 189 278 291 D 274 215 173 193 172 399 319 239 51 239 172 242 245 311 294 311 243 324 368 368 362 295 248 92 290 93 286 203 126 242 189 297 111 192 86 93 326 86 223 232A 325 5176 5176 192

189 86 93 309 357 I I 102 319 179 223 93 92A 362 311 304 274 152 209 189 278 145 189 162 129 129 406 145 189 –Alu –Alu G 172 129 114 227 234 378 290 II 4830 311 294 156 297 362 II12 274 129 293C 295 169 319 262 291 390 248 A M 294 209 +Hae 111 129 311 93 318 –Hinc 298 214 193 223 289 357 F 126 291 145 126 237 234 274 242 III663 148 C 189 188 93 319 269 304 189 I 13262 327 260 397 394 189 266 +Hae 316 R 381 249 271 2601A 766 172 293C 10 +Alu 129 I 10 223 N 192 274 357 184 162 311 I14 263 261 362 93 175 304 93 260 288 +Alu 324 +Ddel 248 357 134 129 I7025 235 –Tru1 344 150 298 93 93 189 184 265T 234 148 93 325 213 –Alu 263A 86 129 320 294 171 51 L3 H 286 111 356 335 184 93 174 234 356 189 304 189 362 164 309 261 354 311 256 145 93 311 295 167 176 188 291 56 327 172 193 293 311 266 (a) (b) 278 93 214 224 Phylogenetic trees of mtDNA haplotypes found in (a) Yakuts, Mongols, and the pooled sample of Central Asian populations (Kazak Mongols, and the pooled sample of Central Yakuts, haplotypes found in (a) trees of mtDNA Phylogenetic Fig. 3. Fig. Koryaks, Itelmen, and Chukcha. Haplotypes are shown with circles (Yakuts, Central Asian populations, Mongols) or squares (Paleo Central with circles (Yakuts, Itelmen, and Chukcha. Haplotypes are shown Koryaks, the haplotype frequency.

MOLECULAR BIOLOGY Vol. 37 No. 4 2003

552 FEDOROVA et al.

Table 4. Common mtDNA haplotypes in Yakuts, Central Asian populations, Mongols, and Paleoasian ethnic groups

Haplo- no. Haplotype group Yakuts Kazakhs [12, 22] Kyrgyz [12] Uighurs [12, 22] Mongols [19] Chukcha [14] Eskimo [14] Koryaks [13] Itelmen [13] 191 82 92 100 103 65 77 147 46 A 1 223, 242, 290, 319 1 4 B 2 86, 136, 189, 217 1 2 C 3 129, 150, 223, 298, 327 2 4 129, 223, 298, 327 6 1 1 1 1 5 148, 164, 223, 288, 298, 327 9 1 6 148, 223, 288, 298, 327 2 2 7 167, 171, 223, 298, 327, 344, 357 1 1 8 171, 223, 298, 327, 344, 357 12 1 1 9 189, 223, 298, 327 1 10 223, 298, 311, 327 8 1 11 223, 298, 327 10 1 1 1 6 12 223, 291, 298, 327 1 13 93, 129, 223, 298, 327 6 2 1 D 14 223, 245, 362 2 1 15 223, 319, 362 4 1 16 223, 362, 368 1 2 17 92, 172, 189, 223, 266, 362 23 1 18 93, 223, 232, 290, 362 1 4 F 19 189, 232A, 249, 304, 311 4 2 1 3 20 172, 189, 232A, 249, 304, 311 4 1 G 21 223, 227, 278, 362 3 2 1 22 223, 227, 234, 278, 362 1 1 H23CRS 34531 24 223, 292 3 1 3 Y 25 126, 231, 266 2 1 and the pooled Central Asian sample. The only excep- agrees with the hypothesis of the southern origin of tion is a branch with nucleotide substitution in posi- Yakuts. tion 16,294. Similar results were obtained with other Comparison of the mitochondrial gene pool for haplogroups, which are represented by a few haplo- Yakuts and modern Paleoasian ethnic groups types in the Yakut mitochondrial gene pool. This (Chukcha, Itelmen, Koryaks) revealed three (8.9%) structure of the tree suggests a common genetic sub- haplotypes common for Yakuts and Koryaks. None of strate, which was formed before the ethnic groups the Chukcha or Itelmen mtDNA haplotypes was found separated. Another evidence for this assumption is in Yakuts. On a phylogenetic tree, Paleoasian mtDNA that the ethnic groups share many mtDNA haplotypes haplotype cluster separately to form Paleoasian-spe- (Table 4). Of the 67 mtDNA haplotypes observed in ciﬁc branches (Fig. 3b). The branches developed and Yakuts, 16 are present in the mitochondrial gene pool diverged in isolation, having virtually no overlap with of the Central Asian population; their total frequency the mtDNA haplotypes of Yakuts, Mongols, or Central in Yakuts is 37.7%. Mongols and Yakuts share Asian populations. Thus, our results are contradictory 11 mtDNA haplotypes, the total frequency of which is to the hypothesis of a substantial Paleoasian contribu- 37.7% in the latter. In total, 55.5% (21) of the Yakut tion to the modern Yakut gene pool. To clarify this mtDNA haplotypes have been found in the gene pools issue, it is necessary to analyze the mtDNA gene pool of the Central Asian and Mongol populations, which in Yukaghirs.

MOLECULAR BIOLOGY Vol. 37 No. 4 2003 ANALYSIS OF MITOCHONDRIAL DNA LINEAGES IN YAKUTS 553

ACKNOWLEDGMENTS 11. Bermisheva M., Tambets K., Villems R., Khusnutdinova E. 2002. Diversity of mitochondrial DNA haplogroups in We are grateful to M.I. Tomskii, Physician-In- ethnic populations of the VolgaÐUral region. Mol. Biol. Chief of Hospital no. 1, Ministry of Health of the 36, 990Ð1001. Sakha Republic; V.I. Kirillina, Head of the Depart- 12. Comas D., Calafell F., Mateu E. et al. 1998. Trading ment of Gene Pool Preservation in Ethnic Groups of genes along the silk road: mtDNA sequences and the ori- the Sakha Republic; and A.N. Nogovitsina, Head of gin of the Central Asian populations. Am. J. Hum. Genet. MGK RB no. 1 for help in collection of the material. 63, 1824Ð1838. This work was supported by the Republican program 13. Schurr T., Sukernik R., Starikovskaya Y. et al. 1999. Development of Human Gene Diagnostics in the Mitochondrial DNA variation in Koryaks and Itelmen: Sakha Republic as part of the collaboration agreement population replacement in the Okhotsk SeaÐBering Sea between the Yakut Research Center and the Estonian region during the neolithic. Am. J. Phys. Anthropol. 108, Biocenter (Tartu). 1Ð39. 14. Starikovskaya Y., Sukernik R., Schurr T. et al. 1998. mtDNA diversity in Chukchi and Siberian Eskimos: REFERENCES implications for the genetic history of Ancient Beringia and the peopling of the New World. Am. J. Hum. Genet. 1. Wallace D.C., Brown M.D., Lott M.T. 1999. Mitochon- 63, 1473Ð1491. drial DNA variation in human evolution and disease. 15. Torroni A., Schurr T., Cabell M. et al. 1993. Asian affini- Gene. 238, 211Ð230. ties and continental radiation of the four founding Native 2. Torroni A., Huoponen K., Francalacci P. et al. 1996. American mtDNAs. Am. J. Hum. Genet. 53, 563Ð590. Classification of European mtDNAs from an analysis of 16. Golubenko M.V., Puzyrev V.P., Salyukov V.B., et al. three European populations. Genetics. 144, 1835Ð1850. 2001. Analysis of the distribution of “Mongoloid” mito- 3. Richards M., Corte-Real H., Forster P. et al. 1996. Pale- chondrial DNA haplotypes in the indigenous population olithic and neolithic lineages in the European mitochon- of the Tuva Republic. Genetika. 37, 831Ð839. drial gene pool. Am. J. Hum. Genet. 59, 185Ð203. 17. Derenko M.V., Denisova G.A., Malyarchuk B.A., et al. 4. Derenko M.V., Shields G.F. 1997. Mitochondrial DNA 2001. The gene pool structure of ethnic groups of the sequence diversity in three North Asian aboriginal pop- AltaiÐSayan Highlands, as inferred from mitochondrial ulation groups. Mol. Biol. 31, 784Ð789. DNA polymorphism. Genetika. 37, 1402Ð1410. 5. Derenko M.V., Shields G.F. 1998. Polymorphism of 18. Ballinger S.W., Schurr T.G., Torroni A. et al. 1992. mitochondrial DNA region V in the indigenous popula- Southeast asian mitochondrial DNA analysis reveals tions of Northern Asia. Genetika. 34, 411Ð415. genetic continuity of ancient mongoloid migration. Genetics. 138, 139Ð152. 6. Meditsinkie laboratornye tekhnologii: spravochnik (Medical Laboratory Techniques: A Handbook). 1999. 19. Kolman C.J., Sambuughin N., Bermingham E. 1996. Ed. Karpishchenko A.I. St. Petersburg: Intermedica. Mitochondrial DNA analysis of mongolian populations and implications for the origin of New World founders. 7. Anderson S., Bankier A.T., Barrell B.G. et al. 1981. Genetics. 142, 1321Ð1334. Sequence and organization of the human mitochondrial genome. Nature. 290, 457Ð465. 20. Kivisild T., Tolk H.-V., Parik J. et al. 2002. The emerging limbs and twigs of the east Asian mtDNA tree. Mol. Biol. 8. Andrews R.M., Kubacka I., Chinnery P.F. et al. 1999. Evol. 19, 1737Ð1751. Reanalysis and revision of the Cambridge reference 21. Derenko M., Malyarchuk B., Dambueva I. et al. 2000. sequence for human mitochondrial DNA. Nature Genet. Mitochondrial DNA variation in two south Siberian 23, 147. aboriginal populations: Implications for the Genetic His- 9. Bandelt H.J., Forster P., Rohl A. 1999. Median-joining tory of North Asia. Human Biol. 72, 945Ð973. networks for inferring intraspecific phylogenies. Mol. 22. Yao Y.-G., Lu X.-M., Luo H.-R. et al. 2000. Gene admix- Biol. Evol. 16, 37Ð48. ture in the Silk Road region of China Ð evidence from 10. Nei M. 1987. Molecular Evolutionary Genetics. NY: mtDNA and melanocortin 1 receptor polymorphism. Columbia Univ. Press. Genes Genet. Syst. 75, 173Ð178.

MOLECULAR BIOLOGY Vol. 37 No. 4 2003