Mitochondrial DNA Variability in Bosnians and Slovenians

Mitochondrial DNA variability in two Slavonic‐speaking populations of the northwestern Balkan peninsula, Bosnians (N = 144) and Slovenians (N = 104), was studied by hypervariable segments I and II (HVS I and II) sequencing and restriction fragment‐length polymorphism (RFLP) analysis of the mtDNA coding region. The majority of the mtDNA detected in Southern Slavonic populations falls into the common West Eurasian mitochondrial haplogroups (e.g., H, pre‐V, J, T, U, K, I, W, and X). About 2% of the Bosnian mtDNAs encompass East Eurasian and African lineages (e.g., M and L1b, respectively). The distribution of mtDNA subclusters in Bosnians, Slovenians and the neighbouring European populations reveals that the common genetic substratum characteristic for Central and Eastern European populations (such as Germans, Poles, Russians and Finns) penetrates also South European territories as far as the Western Balkans. However, the observed differentiation between Bosnian and Slovenian mtDNAs suggests that at least two different migration waves of the Slavs may have reached the Balkans in the early Middle Ages.     

Molecular instability of the mitochondrial haplogroup T sequences at nucleotide positions 16292 and 16296

The mitochondrial haplogroup T, characterized by the nucleotide motif 16126C–16294T in the hypervariable segment I (HVS I), is one of the most frequent among Europeans. It has been shown that this haplogroup includes the only well-resolved subgroup, T1, but that other HVS I sequences cannot be differentiated into subgroups due to possible homoplasies at nucleotide positions 16292, 16296 and 16304, leading to the reticulations in the topology of phylogenetic networks. To study the problem of molecular instability at these positions, we have performed an analysis of 159 previously published West Eurasian HVS I sequences belonging to haplogroup T, together with 12 new HVS I sequences of Eastern Slavs. These 12 sequences represent 16.9% of a total of 71 samples analysed and identified as haplogroup T mtDNAs by RFLP analysis in this study. A search for rare point mutations associated with different combinations of nucleotides 16292T, 16296T and 16304C within the haplogroup T sequences, and specific to certain populations or a group of closely related-by-descent populations, was performed. This analysis revealed 11 marker mutations, each of which was characteristic for a certain group of linguistically or geographically close individuals – the Adygei, Germans, Kazakhs and linguistic isolates of the Eastern Italian Alps. The occurrence of these rare population-specific polymorphisms in association with various combinations of mutations at positions 16292 and 16296 on the haplogroup T background provides evidence of molecular instability at these nucleotide positions. Molecular instability in the haplogroup T HVS I sequences is also suggested by multiple independent losses of the haplogroup T diagnostic nucleotide variants in different populations. The results of the present study suggest that identical haplogroup T HVS I sequence types might have arisen independently in different human populations.     

Reconstructing the phylogeny of African mitochondrial DNA lineages in Slavs

To elucidate the origin of African-specific mtDNA lineages, revealed previously in Slavonic populations (at frequency of about 0.4%), we completely sequenced eight African genomes belonging to haplogroups L1b, L2a, L3b, L3d and M1 gathered from Russians, Czechs, Slovaks and Poles. Results of phylogeographic analysis suggest that at least part of the African mtDNA lineages found in Slavs (such as L1b, L3b1, L3d) appears to be of West African origin, testifying to an opportunity of their occurrence as a result of migrations to Eastern Europe through Iberia. However, a prehistoric introgression of African mtDNA lineages into Eastern Europe (approximately 10 000 years ago) seems to be probable only for European-specific subclade L2a1a, defined by coding region mutations at positions 6722 and 12903 and detected in Czechs and Slovaks. Further studies of the nature of African admixture in gene pools of Europeans require the essential enlargement of databases of African complete mitochondrial genomes.European Journal of Human Genetics (2008) 16, 1091-1096; doi:10.1038/ejhg.2008.70; published online 9 April 2008.     

Mitochondrial DNA Variability in Slovaks, with Application to the Roma Origin

To gain insight into the mitochondrial gene pool diversity of European populations, we studied mitochondrial DNA (mtDNA) variability in 207 subjects from western and eastern areas of Slovakia. Sequencing of two hypervariable segments, HVS I and HVS II, in combination with screening of coding region haplogroup-specific RFLP-markers, revealed that the majority of Slovak mtDNAs belong to the common West Eurasian mitochondrial haplogroups (HV, J, T, U, N1, W, and X). However, a few sub-Saharan African (L2a) mtDNAs were detected in a population from eastern part of Slovakia. In addition, about 3% of mtDNAs from eastern Slovakia encompass Roma-specific lineages. By means of complete mtDNA sequencing we demonstrate here that the Roma-specific M-lineages observed in gene pools of different Slavonic populations (Slovaks, Poles and Russians), belong to Indian-specific haplogroups M5a1 and M35. Moreover, we show that haplogroup J lineages found in gene pools of the Roma and some Slavonic populations (Czechs and Slovaks) belong to new subhaplogroup J1a, which is defined by coding region mutation at position 8460.     

Polymorphisms at locus D1S80 and other hypervariable regions in the analysis of Eastern European ethnic group relationships

BACKGROUND: It has been hypothesized that, whereas many loci are used to generate phylogenetic relationships, the utilization of those that yield the most information could increase the accuracy of any multilocus phylogenetic reconstruction. Among these is the D1S80 hypervariable minisatellite region, which has been shown to be highly polymorphic globally, and it was of interest to compare the nearest neighbours and distant populations of Eastern Europe using the D1S80 polymorphism. AIM: The study evaluated the capacity of the D1S80 locus to discriminate between populations from different ethnic groups in Russia and the Republic of Belarus, revealing the polymorphism parameters of the populations studied. SUBJECTS AND METHODS: Hypervariable D1S80 minisatellite polymorphism was studied in 15 populations, belonging to six distinct ethnic groups from the Russian Federation (Russians, Komis, Maris, Udmurts, Kalmyks, and Yakuts) and the Republic of Belarus (Byelorussians). The data were analysed with other results reported for D1S80 polymorphism among Eastern Europeans, and were analysed together with those previously reported for Eastern European populations for the 3'ApoB, DMPK, DRPLA, and SCA1 hypervariable loci. Genetic diversity analysis was carried out using multidimensional scaling (MDS) of Nei's genetic distances. RESULTS: The Eastern Slavonic populations (Russians, Ukrainians, and Byelorussians) are closely associated, and outermost from populations of Asian origin (Kalmyks and Yakuts). The populations that inhabit the Volga-Ural region (Udmurt, Komi, Mari, and Bashkir ethnic groups) revealed intermediate characteristics. CONCLUSION: The clustering of populations demonstrated here using D1S80 alone coincides with the analysis of five hypervariable region (HVR) loci, and is consistent with linguistic, geographic, and ethnohistorical data. These results are in agreement with most studies of mtDNA, Y-chromosomal, and autosomal DNA diversity in Eastern Europe. The D1S80 locus is convenient for population analyses, and may be used as part of a set of similar markers, which should allow the easy resolution of small differences in population structures.     

Polymorphisms at locus D1S80 and other hypervariable regions in the analysis of Eastern European ethnic group relationships

Background: It has been hypothesized that, whereas many loci are used to generate phylogenetic relationships, the utilization of those that yield the most information could increase the accuracy of any multilocus phylogenetic reconstruction. Among these is the D1S80 hypervariable minisatellite region, which has been shown to be highly polymorphic globally, and it was of interest to compare the nearest neighbours and distant populations of Eastern Europe using the D1S80 polymorphism.

Aim: The study evaluated the capacity of the D1S80 locus to discriminate between populations from different ethnic groups in Russia and the Republic of Belarus, revealing the polymorphism parameters of the populations studied.

Subjects and methods: Hypervariable D1S80 minisatellite polymorphism was studied in 15 populations, belonging to six distinct ethnic groups from the Russian Federation (Russians, Komis, Maris, Udmurts, Kalmyks, and Yakuts) and the Republic of Belarus (Byelorussians). The data were analysed with other results reported for D1S80 polymorphism among Eastern Europeans, and were analysed together with those previously reported for Eastern European populations for the 3′ApoB, DMPK, DRPLA, and SCA1 hypervariable loci. Genetic diversity analysis was carried out using multidimensional scaling (MDS) of Nei's genetic distances.

Results: The Eastern Slavonic populations (Russians, Ukrainians, and Byelorussians) are closely associated, and outermost from populations of Asian origin (Kalmyks and Yakuts). The populations that inhabit the Volga–Ural region (Udmurt, Komi, Mari, and Bashkir ethnic groups) revealed intermediate characteristics.

Conclusion: The clustering of populations demonstrated here using D1S80 alone coincides with the analysis of five hypervariable region (HVR) loci, and is consistent with linguistic, geographic, and ethnohistorical data. These results are in agreement with most studies of mtDNA, Y-chromosomal, and autosomal DNA diversity in Eastern Europe. The D1S80 locus is convenient for population analyses, and may be used as part of a set of similar markers, which should allow the easy resolution of small differences in population structures.     

Mitochondrial DNA variability in Poles and Russians

Mitochondrial DNA (mtDNA) sequence variation was examined in Poles (from the Pomerania-Kujawy region; n = 436) and Russians (from three different regions of the European part of Russia; n = 201), for which the two hypervariable segments (HVS I and HVS II) and haplogroup-specific coding region sites were analyzed. The use of mtDNA coding region RFLP analysis made it possible to distinguish parallel mutations that occurred at particular sites in the HVS I and II regions during mtDNA evolution. In total, parallel mutations were identified at 73 nucleotide sites in HVS I (17.8%) and 31 sites in HVS II (7.73%). The classification of mitochondrial haplotypes revealed the presence of all major European haplogroups, which were characterized by similar patterns of distribution in Poles and Russians. An analysis of the distribution of the control region haplotypes did not reveal any specific combinations of unique mtDNA haplotypes and their subclusters that clearly distinguish both Poles and Russians from the neighbouring European populations. The only exception is a novel subcluster U4a within subhaplogroup U4, defined by a diagnostic mutation at nucleotide position 310 in HVS II. This subcluster was found in common predominantly between Poles and Russians (at a frequency of 2.3% and 2.0%, respectively) and may therefore have a central-eastern European origin.     

Mitochondrial super-haplogroup U diversity in Serbians

Abstract

Background: Available mitochondrial (mtDNA) data demonstrate genetic differentiation among South Slavs inhabiting the Balkan Peninsula. However, their resolution is insufficient to elucidate the female-specific aspects of the genetic history of South Slavs, including the genetic impact of various migrations which were rather common within the Balkans, a region having a turbulent demographic history.

Aim: The aim was to thoroughly study complete mitogenomes of Serbians, a population linking westward and eastward South Slavs.

Subjects and methods: Forty-six predominantly Serbian super-haplogroup U complete mitogenomes were analysed phylogenetically against ～4000 available complete mtDNAs of modern and ancient Western Eurasians.

Results: Serbians share a number of U mtDNA lineages with Southern, Eastern-Central and North-Western Europeans. Putative Balkan-specific lineages (e.g. U1a1c2, U4c1b1, U5b3j, K1a4l and K1a13a1) and lineages shared among Serbians (South Slavs) and West and East Slavs were detected (e.g. U2e1b1, U2e2a1d, U4a2a, U4a2c, U4a2g1, U4d2b and U5b1a1).

Conclusion: The exceptional diversity of maternal lineages found in Serbians may be associated with the genetic impact of both autochthonous pre-Slavic Balkan populations whose mtDNA gene pool was affected by migrations of various populations over time (e.g. Bronze Age pastoralists) and Slavic and Germanic newcomers in the early Middle Ages.     

A Reassessment of Genetic Diversity in Icelanders: Strong Evidence from Multiple Loci for Relative Homogeneity Caused by Genetic Drift

There has been some controversy in the literature concerning whether Icelanders are genetically homogenous or heterogeneous relative to other European populations. We reassess this question in the light of large data sets spanning 83 autosomal SNP loci, 14 serogenetic loci, 6622 Y‐chromosomes and 3214 sequences from mtDNA hypervariable segments 1 and 2 (HVS1 and HVS2). Our results strongly support the hypothesis that genetic drift, with a consequent loss of variation, has had a greater impact on Icelanders than most other Europeans. We also analyse 7245 HVS1 sequences from 25 European populations. In line with other studies, we observe a deficit of rare HVS1 haplotypes and an excess of intermediate frequency haplotypes in Icelanders compared to most European populations, with some measures of genetic diversity indicating relative heterogeneity and others indicating relative homogeneity of Icelanders. Simulations indicate that genetic drift, and not admixture (as proposed by Árnason, 2003 ) is the most likely cause of the atypical Icelandic HVS1 frequency spectrum. These simulations reveal that gene diversity (heterozygosity) and mean pairwise differences are largely insensitive to events in recent population history, while statistics based on the number of haplotypes or segregating sites are much more sensitive. Overall, our analyses strongly indicate that the Icelandic gene pool is less heterogeneous than those of most other European populations.     

Apolipoprotein B 3'-VNTR polymorphism in Eastern European populations

Apolipoprotein B 3' (3' ApoB) minisatellite polymorphism was studied in healthy unrelated individuals from the Russian Federation and the Republic of Belarus, in 10 populations from five ethnic groups: Russians, Byelorussians, Adygeis, Kalmyks and Yakuts. The analysis was carried out using PCR and electrophoresis followed by silver staining. Overall, 25 alleles of the 3' ApoB minisatellite, ranging from 25 to 55 repeats, were detected. Heterozygosity indices were high and varied from 0.73 to 0.84. The distributions of alleles of this minisatellite in the Caucasoid populations (Russians, Byelorussians and Adygeis) had a bimodal character, whereas that for Mongoloid populations (Kalmyks and Yakuts) had a unimodal distribution. Nei's genetic distances between the populations studied and some reference populations of Europe and Asia were estimated. Despite their allele distribution homogeneity, different East Slavonic ethnic groups were clearly resolved by multidimensional analyses. The East Slavonic and Adygei populations revealed a high similarity with European Caucasoids. The Mongoloid populations (Kalmyks and Yakuts) were considerably different from those of the European Caucasoid populations, but were similar to other Asian Mongoloid populations. The results demonstrate the variability of 3' ApoB minisatellite polymorphism not only in distant populations but also, to a certain extent, in genetically relative ones.     

Mutagenesis by Transient Misalignment in the Human Mitochondrial DNA Control Region

To study spontaneous base substitutions in human mitochondrial DNA (mtDNA), we reconstructed the mutation spectra of the hypervariable segments I and II (HVS I and II) using published data on polymorphisms from various human populations. Classification analysis revealed numerous mutation hotspots in HVS I and II mutation spectra. Statistical analysis suggested that strand dislocation mutagenesis, operating in monotonous runs of nucleotides, plays an important role in generating base substitutions in the mtDNA control region. The frequency of mutations compatible with the primer strand dislocation in the HVS I region was almost twice as high as that for template strand dislocation. Frequencies of mutations compatible with the primer and template strand dislocation models are almost equal in the HVS II region. Further analysis of strand dislocation models suggested that an excess of pyrimidine transitions in mutation spectra, reconstructed on the basis of the L‐strand sequence, is caused by an excess of both L‐strand pyrimidine transitions and H‐strand purine transitions. In general, no significant bias toward parent H‐strand‐specific dislocation mutagenesis was found in the HVS I and II regions.     

Different genetic components in the Norwegian population revealed by the analysis of mtDNA and Y chromosome polymorphisms

The genetic composition of the Norwegian population was investigated by analysing polymorphisms associated with both the mitochondrial DNA (mtDNA) and Y chromosome loci in a sample of 74 Norwegian males. The combination of their uniparental mode of inheritance and the absence of recombination make these haplotypic stretches of DNA the tools of choice in evaluating the different components of a population's gene pool. The sequencing of the Dloop and two diagnostic RFLPs (AluI 7025 and HinfI at 12 308) allowed us to classify the mtDNA molecules in 10 previously described groups. As for the Y chromosome the combination of binary markers and microsatellites allowed us to compare our results to those obtained elsewhere in Europe. Both mtDNA and Y chromosome polymorphisms showed a noticeable genetic affinity between Norwegians and central Europeans, especially Germans. When the phylogeographic analysis of the Y chromosome haplotypes was attempted some interesting clues on the peopling of Norway emerged. Although Y chromosome binary and microsatellite data indicate that 80% of the haplotypes are closely related to Central and western Europeans, the remainder share a unique binary marker (M17) common in eastern Europeans with informative microsatellite haplotypes suggesting a different demographic history. Other minor genetic influences on the Norwegian population from Uralic speakers and Mediterranean populations were also highlighted.     

A survey for 32 nucleotide deletion in the CCR-5 chemokine receptor gene (Δccr-5) conferring resistance to human immunodeficiency virus type 1 in different ethnic groups and in chimpanzees

The 32 nucleotide deletion in the CCR-5 chemokine receptor gene referred to as Δccr-5 has been shown to confer resistance to HIV-1. Using PCR, 1,105 human subjects and 33 common chimpanzees were genotyped attributing them to one of the three possible genotypes: wild-type homozygote (w/w); Δccr-5 homozygote (Δccr-5/Δccr-5) and Δccr-5/wild-type heterozygotes (Δccr-5/w). The ethnic groups investigated included different Middle Eastern nationalities (mainly Arab) and Russians. Carriers of the Δccr-5 mutation were found among Arabs, Iranians and Russians. The highest frequency of the mutation was seen in Russians (24.4% of the Δccr-5 heterozygotes, allele frequency–0.1221). Surprisingly, the only Δccr-5 homozygote identified in our study was an Egyptian. The origin of the Δccr-5 mutation in the Middle Eastern populations, both Arab and non-Arab, is most probably due to a gene flow from the Europeans. The frequency of the Δccr-5 mutation in Russians is one of the highest known. It might be one of the factors contributing to a relatively slow pace of increase in the incidence of sexually acquired HIV infection in Russia. None of the chimpanzees tested was positive for Δccr-5. Interestingly, the DNA sequence of the chimpanzee CCR-5 gene in the region including the site of the Δccr-5 mutation, and flanking areas, was virtually identical to the homologous human sequence, only two mismatches (silent substitutions) were found. J. Med. Virol. 55:147–151, 1998. © 1998 Wiley-Liss, Inc.     

Prehistoric and historic traces in the mtDNA of Mozambique: insights into the Bantu expansions and the slave trade

A sample of mitochondrial DNA (mtDNA) from the southeastern African population of Mozambique has been shown to have affinities with populations both to its north and south. From the north came sequences that may have been involved in the Bantu expansion (from western, through eastern, to southern Africa), such as members of haplogroups L3b, L3e1a and a subset of L1a. The dating of the major component of Mozambican mtDNAs, the subset L2a of haplogroup L2, displayed an age range compatible with the Bantu expansion. The southern influence was traced by the presence of sequence types from haplogroup L1d, a probable relict of Khoisan-speaking populations that inhabited the region prior to their displacement by the Bantu-speaking incomers. Within historical times, the forced displacement of Mozambicans as part of the slave trade, mainly documented as being to the Americas, generated a differential input of eastern African sequences into the mtDNA pools of the Americas and of Europe, as testified to by the greater number of sequence matches between Mozambique and the Americas, compared to those between Mozambique and Europe.     

Mitochondrial DNA Diversity in the Polish Roma

Mitochondrial DNA variability in the Polish Roma population has been studied by means of hypervariable segment I and II (HVS I and II) sequencing and restriction fragment‐length polymorphism analysis of the mtDNA coding region. The mtDNA haplotypes detected in the Polish Roma fall into the common Eurasian mitochondrial haplogroups (H, U3, K, J1, X, I, W, and M*). The results of complete mtDNA sequencing clearly indicate that the Romani M*‐lineage belongs to the Indian‐specific haplogroup M5, which is characterized by three transitions in the coding region, at sites 12477, 3921 and 709. Molecular variance analysis inferred from mtDNA data reveals that genetic distances between the Roma groups are considerably larger than those between the surrounding European populations. Also, there are significant differences between the Bulgarian Roma (Balkan and Vlax groups) and West European Roma (Polish, Lithuanian and Spanish groups). Comparative analysis of mtDNA haplotypes in the Roma populations shows that different haplotypes appear to demonstrate impressive founder effects: M5 and H (16261–16304) in all Romani groups; U3, I and J1 in some Romani groups. Interestingly, haplogroup K (with HVS I motif 16224‐16234‐16311) found in the Polish Roma sample seems to be specific for Ashkenazi Jewish populations.     

MtDNA evidence for a genetic bottleneck in the early history of the Ashkenazi Jewish population

The relative roles of natural selection and accentuated genetic drift as explanations for the high frequency of more than 20 Ashkenazi Jewish disease alleles remain controversial. To test for the effects of a maternal bottleneck on the Ashkenazi Jewish population, we performed an extensive analysis of mitochondrial DNA (mtDNA) hypervariable segment 1 (HVS-1) sequence and restriction site polymorphisms in 565 Ashkenazi Jews from different parts of Europe. These patterns of variation were compared with those of five Near Eastern (n=327) and 10 host European (n=849) non-Jewish populations. Only four mtDNA haplogroups (Hgs) (defined on the basis of diagnostic coding region RFLPs and HVS-1 sequence variants) account for approximately 70% of Ashkenazi mtDNA variation. While several Ashkenazi Jewish mtDNA Hgs appear to derive from the Near East, there is also evidence for a low level of introgression from host European non-Jewish populations. HVS-1 sequence analysis revealed increased frequencies of Ashkenazi Jewish haplotypes that are rare or absent in other populations, and a reduced number of singletons in the Ashkenazi Jewish sample. These diversity patterns provide evidence for a prolonged period of low effective size in the history of the Ashkenazi population. The data best fit a model of an early bottleneck (approximately 100 generations ago), perhaps corresponding to initial migrations of ancestral Ashkenazim in the Near East or to Europe. A genetic bottleneck followed by the recent phenomenon of rapid population growth are likely to have produced the conditions that led to the high frequency of many genetic disease alleles in the Ashkenazi population.     

Mitochondrial DNA sequences in prehistoric human remains from the Alps

The spread of agriculture that started in the Near East about 10 000 years ago caused a dramatic change in the European archaeological record. It is still unclear if that change was caused mostly by movement of people or by cultural transformations. In particular, there is disagreement on what proportion of the current European gene pool is derived either from the pre-agricultural, paleolithic and mesolithic people, or from neolithic farmers immigrating from the south-east. To begin to characterise the mtDNA gene pool of prehistoric Europe we examined five human remains from the Eastern Italian Alps, dated between 14 000 and 3000 years ago. Three of them yielded sufficient amount of mtDNA for analysis. DNA extracts were prepared in two independent laboratories, and PCR products from the first hypervariable segment of the mtDNA control region were cloned and sequenced. Together with the 5200 year old 'ice man', these DNA sequences show that European mtDNA diversity was already high at the beginning of the neolithic period. All the neolithic sequences have been observed in contemporary Europeans, suggesting genealogical continuity between the neolithic and present-day European mtDNA gene pool. The mtDNA sequence from a 14 000 year-old specimen was not observed in any contemporary Europeans, raising the possibility of a lack of continuity between the mesolithic and present-day European gene pools.     

Y-STR variation among Slavs: evidence for the Slavic homeland in the middle Dnieper basin

A set of 18 Y-chromosomal microsatellite loci was analysed in 568 males from Poland, Slovakia and three regions of Belarus. The results were compared to data available for 2,937 Y chromosome samples from 20 other Slavic populations. Lack of relationship between linguistic, geographic and historical relations between Slavic populations and Y-short tandem repeat (STR) haplotype distribution was observed. Two genetically distant groups of Slavic populations were revealed: one encompassing all Western-Slavic, Eastern-Slavic, and two Southern-Slavic populations, and one encompassing all remaining Southern Slavs. An analysis of molecular variance (AMOVA) based on Y-chromosomal STRs showed that the variation observed between the two population groups was 4.3%, and was higher than the level of genetic variance among populations within the groups (1.2%). Homogeneity of northern Slavic paternal lineages in Europe was shown to stretch from the Alps to the upper Volga and involve ethnicities speaking completely different branches of Slavic languages. The central position of the population of Ukraine in the network of insignificant AMOVA comparisons, and the lack of traces of significant contribution of ancient tribes inhabiting present-day Poland to the gene pool of Eastern and Southern Slavs, support hypothesis placing the earliest known homeland of Slavs in the middle Dnieper basin.     

Y-Chromosome distribution within the geo-linguistic landscape of northwestern Russia

Populations of northeastern Europe and the Uralic mountain range are found in close geographic proximity, but they have been subject to different demographic histories. The current study attempts to better understand the genetic paternal relationships of ethnic groups residing in these regions. We have performed high-resolution haplotyping of 236 Y-chromosomes from populations in northwestern Russia and the Uralic mountains, and compared them to relevant previously published data. Haplotype variation and age estimation analyses using 15 Y-STR loci were conducted for samples within the N1b, N1c1 and R1a1 single-nucleotide polymorphism backgrounds. Our results suggest that although most genetic relationships throughout Eurasia are dependent on geographic proximity, members of the Uralic and Slavic linguistic families and subfamilies, yield significant correlations at both levels of comparison making it difficult to denote either linguistics or geographic proximity as the basis for their genetic substrata. Expansion times for haplogroup R1a1 date approximately to 18 000 YBP, and age estimates along with Network topology of populations found at opposite poles of its range (Eastern Europe and South Asia) indicate that two separate haplotypic foci exist within this haplogroup. Data based on haplogroup N1b challenge earlier findings and suggest that the mutation may have occurred in the Uralic range rather than in Siberia and much earlier than has been proposed (12.9±4.1 instead of 5.2±2.7 kya). In addition, age and variance estimates for haplogroup N1c1 suggest that populations from the western Urals may have been genetically influenced by a dispersal from northeastern Europe (eg, eastern Slavs) rather than the converse.