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.     

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.     

Mitochondrial DNA variability in Russians and Ukrainians: Implication to the origin of the Eastern Slavs

In order to investigate the origin of the Eastern Slavs, mitochondrial DNA (mtDNA) sequence variation was examined in Russians and Ukrainians by hypervariable segment I (HVS I) sequencing and restriction analysis of the haplogroup-specific sites. No significant differences were found for Russians and Ukrainians when compared to other Europeans – in fact, they fall within the range of gene diversity seen throughout Europe and exhibit the unimodal pattern of pairwise sequence differences. Moreover, HVS I sequences in the Russians and Ukrainians are similar or identical to those found in eastern and western European populations. Despite the small genetic distances between Europeans, phylogenetic analysis reveals a considerable heterogeneity of Eastern Slavonic populations – they do not cluster together onto a phylogenetic tree. Analysis of distribution of rare HVS I types shared between populations of Eastern Slavs and other West Eurasians has shown that Russians share rare haplotypes mainly with Germans and Finno–Ugric populations. Of these, subhaplogroup H1 sequence types, which are defined by different combinations of nucleotides 16192T, 16294T, 16304C, 16311C and 16320T, are found predominantly in common between Russians and German-speaking populations. The data obtained allow us to conclude that the Slavonic migrations in early Middle Ages from their putative homeland in central Europe to the east of Europe were accompanied mostly by the same mtDNA types characteristic for the pre-Slavonic populations of eastern Europe.     

Maternal Genetic Heritage of Southeastern Europe Reveals a New Croatian Isolate and a Novel,Local Sub‐Branching in the X2 Haplogroup

High mtDNA variation in Southeastern Europe (SEE) is a reflection of the turbulent and complex demographic history of this area, influenced by gene flow from various parts of Eurasia and a long history of intermixing. Our results of 1035 samples (488 from Croatia, 239 from Bosnia and 130 from Herzegovina, reported earlier, and 97 Slovenians and 81 individuals from ?umberak, reported here for the first time) show that the SEE maternal genetic diversity fits within a broader European maternal genetic landscape. The study also shows that the population of ?umberak, located in the continental part of Croatia, developed some unique mtDNA haplotypes and elevated haplogroup frequencies due to distinctive demographic history and can be considered a moderate genetic isolate. We also report seven samples from the Bosnian population and one Herzegovinian sample designated as X2* individuals that could not be assigned to any of its sublineages (X2a'o) according to the existing X2 phylogeny. In an attempt to clarify the phylogeny of our X2 samples, their mitochondrial DNA has been completely sequenced. We suppose that these lineages are signs of local microdifferentiation processes that occurred in the recent demographic past in this area and could possibly be marked as SEE‐specific X2 sublineages.     

Diversity of Mitochondrial DNA Lineages in South Siberia

To investigate the origin and evolution of aboriginal populations of South Siberia, a comprehensive mitochondrial DNA (mtDNA) analysis (HVR1 sequencing combined with RFLP typing) of 480 individuals, representing seven Altaic‐speaking populations (Altaians, Khakassians, Buryats, Sojots, Tuvinians, Todjins and Tofalars), was performed. Additionally, HVR2 sequence information was obtained for 110 Altaians, providing, in particular, some novel details of the East Asian mtDNA phylogeny. The total sample revealed 81% East Asian (M*, M7, M8, M9, M10, C, D, G, Z, A, B, F, N9a, Y) and 17% West Eurasian (H, U, J, T, I, N1a, X) matrilineal genetic contribution, but with regional differences within South Siberia. The highest influx of West Eurasian mtDNAs was observed in populations from the East Sayan and Altai regions (from 12.5% to 34.5%), whereas in populations from the Baikal region this contribution was markedly lower (less than 10%). The considerable substructure within South Siberian haplogroups B, F, and G, together with the high degree of haplogroup C and D diversity revealed there, allows us to conclude that South Siberians carry the genetic imprint of early‐colonization phase of Eurasia. Statistical analyses revealed that South Siberian populations contain high levels of mtDNA diversity and high heterogeneity of mtDNA sequences among populations (Fst = 5.05%) that might be due to geography but not due to language and anthropological features.     

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.     

Joining the Pillars of Hercules: mtDNA Sequences Show Multidirectional Gene Flow in the Western Mediterranean

Phylogenetic analysis of mitochondrial DNA (mtDNA) performed in Western Mediterranean populations has shown that both shores share a common set of mtDNA haplogroups already found in Europe and the Middle East. Principal co‐ordinates of genetic distances and principal components analyses based on the haplotype frequencies show that the main genetic difference is attributed to the higher frequency of sub‐Saharan L haplogroups in NW Africa, showing some gene flow across the Sahara desert, with a major impact in the southern populations of NW Africa. The AMOVA demonstrates that SW European populations are highly homogeneous whereas NW African populations display a more heterogeneous genetic pattern, due to an east‐west differentiation as a result of gene flow coming from the East. Despite the shared haplogroups found in both areas, the European V and the NW African U6 haplogroups reveal the traces of the Mediterranean Sea permeability to female migrations, and allowed for determination and quantification of the genetic contribution of both shores to the genetic landscape of the geographic area. Comparison of mtDNA data with autosomal markers and Y‐chromosome lineages, analysed in the same populations, shows a congruent pattern, although female‐mediated gene flow seems to have been more intense than male‐mediated gene flow.     

Pattern of mtDNA Variation in Three Populations from São Tomé e Príncipe

We have analysed the matrilineal genetic composition of three self‐reported ethnic groups from São Tomé e Príncipe (Gulf of Guinea), an African archipelago whose settlement begun in the late fifteenth century. Sequence data from the hypervariable segments I (HVS‐I) and II (HVS‐II) were obtained for 30 Angolares, 35 Forros and 38 Tongas. The repertory of mtDNA lineages in São Tomé e Príncipe denoted a fully African maternal pool, primarily arisen from a Central/Southwestern substratum. The absence of any lineages of putative European descent means that the European impact at the mitochondrial pool was virtually nil. Angolares showed a clear reduction of mtDNA diversity and a slight genetic differentiation relative to Tongas or Forros, whereas the latter two groups did not present any signs of genetic boundaries between each other. The data obtained here reinforce the depiction of genetic substructuring in São Tomé e Príncipe previously derived from Y‐chromosome STRs. In addition, the crossing of mtDNA and Y‐STR information led to the inference that the female mediated gene flow within the archipelago was less restricted than the male, a pattern that could be framed in the cultural traditions and socio‐historical interactions among the groups.     

Northwest Siberian Khanty and Mansi in the junction of West and East Eurasian gene pools as revealed by uniparental markers

Northwest Siberia is geographically remote territory, which has been settled by indigenous human populations probably since the Upper Paleolithic. To investigate the genetic landscape of Northwest Siberians, we have analyzed mitochondrial and Y chromosome DNA polymorphisms of 169 unrelated individuals from Khanty and Mansi ethnic groups in Northwest Siberia. In addition, HVS-I sequences (N = 3522) and Y chromosome SNP data (N = 2175), obtained from the literature, were used to elucidate the genetic relationships among the North Eurasian populations. The results show clinal distributions of mtDNA and Y chromosome haplogroups along East-West axis of Northern Eurasia. In this context, the Ugric-speaking Khanty and Mansi appear as unique intermediate populations carrying Upper Paleolithic and more recent haplotypes typical for both West and East Eurasian gene pools. This admixture indicates that the Khanty and Mansi populations have resided in the contact zone of genetically distinguishable eastern and western Eurasia.     

Analysis of mtDNA HVRII in several human populations using an immobilised SSO probe hybridisation assay.

Several populations were typed for the hypervariable region II (HVRII) of the mitochondrial DNA (mtDNA) control region using immobilised sequence-specific oligonucleotide (SSO) probes. A total of 16 SSO probes was used to type 1081 individuals from eight different ethnic groups (African Americans, Somali, US Europeans, US Hispanics, Bosnians, Finns, Saami and Japanese). Data was compared with already published sequence data by analysis of principal components, genetic distances and analysis of the molecular variance (AMOVA). The analyses performed group the samples in several clusters according to their geographical origins. Most of the variability detected is assigned to differences between individuals and only 7% is assigned to differences among groups of populations within and between geographical regions. Several features are patent in the samples studied: Somali, as a representative East African population, seem to have experienced a detectable amount of Caucasoid maternal influence; different degrees of admixture in the US samples studied are detected; Finns and Saami belong to the European genetic landscape, although Saami present an outlier position attributable to a strong maternal founder effect. The technique used is a rapid and simple method to detect human variation in the mtDNA HVRII in a large number of samples, which might be useful in forensic and population genetic studies.     

Mitochondrial DNA Portrait of Latvians: Towards the Understanding of the Genetic Structure of Baltic-Speaking Populations

Mitochondrial DNA (mtDNA) variation was investigated in a sample of 299 Latvians, a Baltic-speaking population from Eastern Europe. Sequencing of the first hypervariable segment (HVS-I) in combination with analysis of informative coding region markers revealed that the vast majority of observed mtDNAs belong to haplogroups (hgs) common to most European populations. Analysis of the spatial distribution of mtDNA haplotypes found in Latvians, as well as in Baltic-speaking populations in general, revealed that they share haplotypes with all neighbouring populations irrespective of their linguistic affiliation. Hence, the results of our mtDNA analysis show that the previously described sharp difference between the Y-chromosomal hg N3 distribution in the paternally inherited gene pool of Baltic-speaking populations and of other European Indo-European speakers does not have a corresponding maternal counterpart.     

Admixture, migrations, and dispersals in Central Asia: evidence from maternal DNA lineages

Mitochondrial DNA (mtDNA) lineages of 232 individuals from 12 Central Asian populations were sequenced for both control region hypervariable segments, and additional informative sites in the coding region were also determined. Most of the mtDNA lineages belong to branches of the haplogroups with an eastern Eurasian (A, B, C, D, F, G, Y, and M haplogroups) or a western Eurasian (HV, JT, UK, I, W, and N haplogroups) origin, with a small fraction of Indian M lineages. This suggests that the extant genetic variation found in Central Asia is the result of admixture of already differentiated populations from eastern and western Eurasia. Nonetheless, two groups of lineages, D4c and G2a, seem to have expanded from Central Asia and might have their Y-chromosome counterpart in lineages belonging to haplotype P(xR1a). The present results suggest that the mtDNA found out of Africa might be the result of a maturation phase, presumably in the Middle East or eastern Africa, that led to haplogroups M and N, and subsequently expanded into Eurasia, yielding a geographically structured group of external branches of these two haplogroups in western and eastern Eurasia, Central Asia being a contact zone between two differentiated groups of peoples.     

Site 73 in hypervariable region II of the human mitochondrial genome and the origin of European populations

The majority of published human mitochondrial DNA sequence data are confined to hypervariable region I in the control region. By contrast, this paper focusses on a nucleotide site in hypervariable region II. Unlike most non-European populations whose mtDNA sequences have been studied in the literature, the British 'white Caucasian' population has a high level of variation at site 73 (following the site numbering by Anderson et al. 1981). This variation appears to have its origin largely in a mutation from guanine to adenine at that site with an estimated minimum age between 15000 and 25000 years. The data of Piercy et al. (1993) suggest that roughly half of the British 'white Caucasian' mitochondrial gene pool is descended from a common maternal ancestor who carried this mutation at site 73. This site also plays a central role in distinguishing the five major European mtDNA clusters identified in Richards et al. (1996). We suggest that the lineages carrying an A at site 73, together with some other lineages, may have their origins in a small founder population which expanded after the last glacial maximum about 20000 years ago. We conclude that, in addition to region I sequences, site 73 is worth determining in studies of Caucasian populations.     

Mitochondrial haplogroup C in ancient mitochondrial DNA from Ukraine extends the presence of East Eurasian genetic lineages in Neolithic Central and Eastern Europe

Recent studies of ancient mitochondrial DNA (mtDNA) lineages have revealed the presence of East Eurasian mtDNA haplogroups in the Central European Neolithic. Here we report the finding of East Eurasian lineages in ancient mtDNA from two Neolithic cemeteries of the North Pontic Region (NPR) in Ukraine. In our study, comprehensive haplotyping information was obtained for 7 out of 18 specimens. Although the majority of identified mtDNA haplogroups belonged to the traditional West Eurasian lineages of H and U, three specimens were determined to belong to the lineages of mtDNA haplogroup C. This find extends the presence of East Eurasian lineages in Neolithic Europe from the Carpathian Mountains to the northern shores of the Black Sea and provides the first genetic account of Neolithic mtDNA lineages from the NPR.     

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.     

Mitochondrial DNA analysis reveals diverse histories of tribal populations from India

We analyzed 370 bp of the first hypervariable region of the mitochondrial DNA (mtDNA) control region in 752 individuals from 17 tribal and four nontribal groups from the Indian subcontinent, to address questions concerning the origins, genetic structure and relationships of these groups. Southern Indian tribes showed reduced diversity and large genetic distances, both among themselves and when compared with other groups, and no signal of prehistoric demographic expansions. These results probably reflect enhanced genetic drift because of small population sizes and/or bottlenecks in these groups. By contrast, northern groups exhibited more diversity and signals of prehistoric demographic expansions. Phylogenetic analyses revealed that southern and northern groups (except northeastern ones) have related mtDNA sequences albeit at different frequencies, further supporting the larger impact of drift on the genetic structure of southern groups. The Indian mtDNA gene pool appears to be more closely related to the east Eurasian gene pool (including central, east and southeast Asian populations) than the west Eurasian one (including European and Caucasian populations). Within India, northeastern tribes are quite distinct from other groups; they are more closely related to east Asians than to other Indians. This is consistent with linguistic evidence in that these populations speak Tibeto-Burman languages of east Asian origin. Otherwise, analyses of molecular variance suggested that caste and tribal groups are genetically similar with respect to mtDNA variation.     

Review of Croatian genetic heritage as revealed by mitochondrial DNA and Y chromosomal lineages

The aim of this review is to summarize the existing data collected in high-resolution phylogenetic studies of mitochondrial DNA and Y chromosome variation in mainland and insular Croatian populations. Mitochondrial DNA polymorphisms were explored in 721 individuals by sequencing mtDNA HVS-1 region and screening a selection of 24 restriction fragment length polymorphisms (RFLPs), diagnostic for main Eurasian mtDNA haplogroups. Whereas Y chromosome variation was analyzed in 451 men by using 19 single nucleotide polymorphism (SNP)/indel and 8 short tandem repeat (STR) loci. The phylogeography of mtDNA and Y chromosome variants of Croatians can be adequately explained within typical European maternal and paternal genetic landscape, with the exception of mtDNA haplogroup F and Y-chromosomal haplogroup P* which indicate a connection to Asian populations. Similar to other European and Near Eastern populations, the most frequent mtDNA haplogroups in Croatians were H (41.1%), U5 (10.3%), and J (9.7%). The most frequent Y chromosomal haplogroups in Croatians, I-P37 (41.7%) and R1a-SRY1532 (25%), as well as the observed structuring of Y chromosomal variance reveal a clearly evident Slavic component in the paternal gene pool of contemporary Croatian men. Even though each population and groups of populations are well characterized by maternal and paternal haplogroup distribution, it is important to keep in mind that linking phylogeography of various haplogroups with known historic and prehistoric scenarios should be cautiously performed.     

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.     

Association between mitochondrial DNA haplogroup and myelodysplastic syndromes

Polymorphisms in mitochondrial DNA (mtDNA) are used to group individuals into haplogroups reflecting human global migration and are associated with multiple diseases, including cancer. Here, we evaluate the association between mtDNA haplogroup and risk of myelodysplastic syndromes (MDS). Cases were identified by the Minnesota Cancer Surveillance System. Controls were identified through the Minnesota State driver's license/identification card list. Because haplogroup frequencies vary by race and ethnicity, we restricted analyses to non‐Hispanic whites. We genotyped 15 mtSNPs that capture common European mitochondrial haplogroup variation. We used SAS v.9.3 (SAS Institute, Cary, NC) to calculate odds ratios (OR) and 95% confidence intervals (CI) overall and stratified by MDS subtype and IPSS‐R risk category. We were able to classify 215 cases with confirmed MDS and 522 controls into one of the 11 common European haplogroups. Due to small sample sizes in some subgroups, we combined mt haplogroups into larger bins based on the haplogroup evolutionary tree, including HV (H + V), JT (J + T), IWX (I + W + X), UK (U + K), and Z for comparisons of cases and controls. Using haplogroup HV as the reference group, we found a statistically significant association between haplogroup JT and MDS (OR = 0.58, 95% CI 0.36, 0.92, P = 0.02). No statistically significant heterogeneity was observed in subgroup analyses. In this population‐based study of MDS, we observed an association between mtDNA haplogroup JT and risk of MDS. While previously published studies provide biological plausibility for the observed association, further studies of the relationship between mtDNA variation and MDS are warranted in larger sample sizes. © 2016 Wiley Periodicals, Inc.     

Immunoglobulin allotypes in Southwest Asia: Populations at the Crossroads

Southwest Asia has a long history of contact with Central Asian and with Sub‐Saharan African populations. Is the genetic structure of these populations reflective of these historical facts? To study this, data was generated on the immunoglobulin heavy chain (GM) and light chain (KM) allotypes from seven Arab and three non‐Arab populations in SW Asia to examine the relationship of these populations to SE European, NW Indian, Sub‐Saharan African, and Central Asian populations. Like mtDNA and Y chromosome markers, the GM haplotypes are largely continent specific making them an excellent tool for the detection of gene flow whereas the KM markers are less informative. Six of the nine GM haplotypes detected in SW Asians are Indo‐European, Sub‐Saharan African, or East Asian specific. The allotype results indicate variable but significantly higher Sub‐Saharan African gene flow in Arab populations (average 26.9%; 15.0–61.6%) vs. the non‐Arab populations (average 7.3%; 9.0–13.4%), but higher levels of Central Asian gene flow in the non‐Arab populations (average 28.8%; 10.5–48.8%) vs. the Arab populations (average 9.0%; 0.0–26.4%). Principal components analysis and hierarchical cluster analysis based on the immunoglobulin allotypes are consistent with the historical population contacts of this part of the world and reflect the power of the GM haplotypes in dissecting population relationships. However, the KM*1 frequencies were only correlated with the degree of African gene flow (Pearson r = 0.69, P = 0.026) in SW Asian populations. Am. J. Hum. Biol., 2008. © 2008 Wiley‐Liss, Inc.