To address this question, we chose to survey the remnants of the Mansi, a tribal group of sedentary fishers and hunters who, for ages, inhabited the pine-birch boreal forests on the eastern slope of the Ural Mountains, the provisional geographic barrier separating Asia and Europe. The Mansi speak a dialect of the Finno-Ugric language of the Uralic linguistic family, to which the Saami language also belongs (Fedorova et al. ¹⁹⁹⁴).

Blood samples were collected from 59 Mansi in the villages of Shaim, Chantarya, Polovinka, and Shugur, which are scattered along the Konda River and its tributaries. An additional 39 samples were collected from the tiny settlements of Shshekurya, Lombovozh, and Sos’va, in the northern Sos’va River/Lyamin River basin (fig. 1).

Figure 1 A map of northwestern Siberia, indicating the locations of the two Mansi populations sampled.

mtDNA variation was surveyed by digestion with 19 restriction endonucleases, sequencing of hypervariable segments I and II (HVS-I and HVS-II, respectively) of the control region, and sequence detection of diagnostic polymorphic sites at nucleotide positions 7600, 12308, and 12705 (Torroni et al. ¹⁹⁹⁸). The 98 Mansi mtDNA samples proved to be a novel mixture of 63% European mtDNA samples and 37% Asian-Siberian mtDNA samples. Of 62 European mtDNA samples, 28 harbored the characteristic 12308G coding-region mutation, indicating that they belong to haplogroup U; of the haplogroup U mtDNA samples, 16 harbored the diagnostic markers of subhaplogroup U4, including the RsaI-site gain at nucleotide position 4643 (i.e., 4643 RsaI+), 11329 AluI+, and the control-region 16356C mutation. An additional four mtDNA samples were assigned to the U5a subcluster, which is characterized by the 16256T and 16270T control-region motif, and five belonged to the U7 subcluster, which is characterized by the 16309G transition and the 16318T transversion. However, the Mansi lacked the U5b1 subcluster defined by the “Saami motif” of 16144C, 16189C, and 16270T control-region variants. Only three mtDNA samples belonged to subhaplogroup K of haplogroup U (tables 1 and 2).

Table 1 mtDNA Diversity in the Mansi[Note]

Table 2 Frequencies (%) of mtDNA Types in the Mansi in Comparison with the Saami and Finns[Note]

The mtDNA samples that belonged to haplogroup TJ were also well represented in the Mansi and encompassed 7 and 12 mtDNA samples, respectively. The ancestral 4216 NlaIII+ and 16126C variants of haplogroup T (fig. 2) were found in the Mansi and also in the Finnish TJ phylogeny (Finnila et al. ²⁰⁰¹). Two individuals of sublineage T and one individual of sublineage T1 appeared to have novel mtDNA haplotypes, including a previously undescribed site loss, 13704 BstNI−. Haplogroup J was confined to two sublineages, J2 and the rare J1b1 sublineage. The J2 mtDNA samples were found in 10.2% of the Mansi, even though they are rarely observed in other European populations, including the Saami and Finns (table 2). J1b1 was observed in two individuals.

Figure 2 Schematic phylogenetic representation of mtDNA lineages found in the Mansi. The sizes of the circles, which denote lineages, are proportional to the number of sampled individuals. Mutations are transitions unless otherwise specified. Squares denote the (more ...)

Haplogroup H, found in >40% of western Europeans, was present in only 14.3% of the Mansi mtDNA samples. Still, several sublineages of haplogroup H were observed, including six mtDNA samples of haplogroup H3, characterized by the 7025 AluI−, 14766 MseI− coding plus the 16189C and 16356C or 16189C control-region variants. An additional three Mansi mtDNA samples belonged to haplogroup H2, as indicated by the 4769 AluI+ variant and an HVS-I sequence identical to the Cambridge reference sequence (Andrews et al. ¹⁹⁹⁹). Two of these three mtDNA samples also had the 8858 HhaI+. Finally, five of the haplogroup H mtDNA samples belonged to a unique, previously unreported variant (haplogroup H*) distinguished by the 16169T and 16184T control-region variants, in HVS-I, and the 73G variant, in HVS-II. Since the 73 site in HVS-II varies among the Mansi haplogroup H mtDNA samples, as well as among the Finnish mtDNA samples and other European mtDNA samples, it appears to be a hypervariable site (Finnila et al. ²⁰⁰¹; Helgason et al. ²⁰⁰¹). Therefore, we disregarded the 73 site for phylogenetic reconstruction (fig. 2). Thus, the structure of the haplogroup H mtDNA types in the Mansi is very similar to that in the Finns.

Haplogroup V was found in only one Mansi mtDNA sample. This mtDNA type was characterized by 4577 NlaIII−, 14766 MseI−, and the 16298C and 72C variants (table 1). Haplogroup V is at its highest frequency, 39.8%, among the Saami and has frequencies of 5.1% among Finns (table 2) and 2.6% among Russians from the Upper Volga River region (Malyarchuk et al. ²⁰⁰¹). Hence, this Mansi haplogroup V mtDNA type could be due to gene flow from western Uralic speakers or Russian colonizers.

Among the 36 (37%) Mansi mtDNA samples that belong to traditional Asian haplogroups, 17 Mansi mtDNA samples harbored mtDNA of haplogroup C. One haplogroup C mtDNA type found in four individuals is missing the characteristic 16223T transition, presumably because of a reverse mutation. Eight of the Mansi mtDNA samples belonged to haplogroup D. One of these lacked the classically associated 10394 DdeI+/10397 AluI+ sites, which characterize macrohaplogroup M (at the RFLP level), which encompasses haplogroups C and D. Sequencing of the segment encompassing this region revealed the expected macrohaplogroup M 10398G and 10400T transitions. However, a 10397G transition was also found that would account for the simultaneous elimination of the adjacent restriction sites. Finally, single mtDNAs of haplogroups G and F and the unclassified M (i.e., M*) haplogroup were found in the Mansi. These may also be due to recent gene flow.

Thus, this study revealed that the Mansi possess a unique combination of western European and eastern Siberian mtDNA lineages. The novel distribution and subtypes of haplogroup U make it unlikely that this is the result of recent gene flow from modern Europeans. Rather, the Mansi mtDNA pool may contain traces of the ancient proto-Eurasian hunting-gathering populations that originally colonized the trans-Ural region and adjacent part of Siberia. In this regard, the most distinctive feature of the Mansi mtDNA samples is the high frequency (16.3%) of subhaplogroup U4. Neither U4 nor U5 subhaplogroups are common in the Middle East (Macaulay et al. ¹⁹⁹⁹), and subhaplogroup U4 attains its highest frequency (28.9%) in the Ket of the Yenisey River (authors’ unpublished data). Hence, subhaplogroup U4 may be indicative of the remnants of Upper Paleolithic populations of Europeans preserved just east of the Ural Mountains.

The presence of subhaplogroup U7 in the Mansi supports the conjecture of its proto-Eurasian origin ~24,000–54,000 years ago (Richards et al. ²⁰⁰⁰). Subhaplogroup U7 is virtually absent from modern Europeans and is absent or extremely rare in western Uralic-speaking populations, such as the Finns and Saami (Helgason et al. ²⁰⁰¹; Meinila et al. ²⁰⁰¹). However, subhaplogroup U7 is present in the Middle East, although in very low frequencies (Richards et al. ²⁰⁰⁰). Thus, in the Mansi, subhaplogroup U7 could be a part of Paleolithic dispersals from the Middle East, whose traces have not been erased by subsequent migrations. This conjecture is supported by the presence in the Mansi of subhaplogroup J2, which may indicate a Neolithic phase expansion toward the Ural Mountains.

Although the core of genetic makeup of the Mansi consisted of mtDNA types that apparently were ancient European, 29% of the Mansi mtDNA samples are from three of the four haplogroups that define the migration from Siberia to the Americas (i.e., haplogroups A, C, and D). Such a novel genetic structure could represent the recent amalgamation of western and eastern populations. Alternatively, the Mansi may reflect a more ancient and uniform distribution of mtDNA lineages that subsequently became more specialized as a result of later genetic drift or environmental selection. Whichever event proves to be the case, it is clear that further surveys of trans-Ural and Siberian mtDNA will yield much information about the genetic history of northern Eurasia and the origins of Uralic-speaking populations.

We are indebted to the Mansi people who, after providing informed consent, allowed us to draw blood and provided with the family histories. We would like to thank Dr. Kari Majamaa (University School of Medicine, Oulu, Finland) for access to his paper prior to its publication and Dr. Robert S. Hoffmann (Smithsonian Institution, Washington DC) for his helpful comments on an earlier draft of the manuscript. This research received support from INTAS (the International Association for the Promotion of Cooperation with Scientists from the New Independent States of the Former Soviet Union [European Community, Brussels, Belgium]) grant 96-1766 and National Institutes of Health grants TW1175 (to R.I.S.) and NS21328, AG13154, NS41850, and HL64017 (to D.C.W.).