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In contrast with the traditional methods applied to assessment of population diversity, high-throughput sequencing technologies have a wider application in clinical practice with greater potential to find novel disease-causing variants for multifactorial disorders. Widely used test panels may not meet their goal to diagnose the patient’s condition with a full reliability since this method often does not take into account the population frequencies of analyzed genetic markers. Here, we analyzed 57 male individuals of five ethnic groups from Russia and Tajikistan using the whole exome sequencing technique (Ion AmpliSeq Exome), which resulted in detecting more than 299,000 single nucleotide polymorphisms. Samples formed clusters on the PCA plot according to the geographical location of the corresponding populations. Thereby, the methodology of whole-exome sequencing, in general, and the Ion AmpliSeq Exome panel, in particular, could be positively applied for the purposes of population genetics and for detection of the novel clinically relevant variants.

We conducted the first genetic analysis of a wide a range of rural Russian populations in European Russia with a panel of common DNA markers commonly used in criminalistics genetic identification. We examined a total of 647 samples from indigenous ethnic Russian populations in Arkhangelsk, Belgorod, Voronezh, Kursk, Rostov, Ryazan, and Orel regions. We employed a multiplex genotyping kit, COrDIS Plus, to genotype Short Tandem Repeat (STR) loci, which included the genetic marker panel officially recommended for DNA identification in the Russian Federation, the United States, and the European Union. In the course of our study, we created a database of allelic frequencies, examined the distribution of alleles and genotypes in seven rural Russian populations, and defined the genetic relationships between these populations. We found that, although multidimensional analysis indicated a difference between the Northern gene pool and the rest of the Russian European populations, a pairwise comparison using 19 STR markers among all populations did not reveal significant differences. This is in concordance with previous studies, which examined up to 12 STR markers of urban Russian populations. Therefore, the database of allelic frequencies created in this study can be applied for forensic examinations and DNA identification among the ethnic Russian population over European Russia. We also noted a decrease in the levels of heterozygosity in the northern Russian population compared to ethnic populations in southern and central Russia, which is consistent with trends identified previously using classical gene markers and analysis of mitochondrial DNA.

The origins of the First Americans remain contentious. Although Native Americans seem to be genetically most closely related to east Asians1–3, there is no consensus with regard to which specific Old World populations they are closest to4–8. Here we sequence the draft genome of an approximately 24,000-year-old individual (MA-1), from Mal’ta in south-central Siberia9, to an average depth of 13. To our knowledge this is the oldest anatomically modern human genome reported to date. The MA-1 mitochondrial genome belongs to haplogroup U, which has also been found at high frequency among Upper Palaeolithic and Mesolithic European hunter-gatherers10–12, and the Y chromosome of MA-1 is basal to modern-day western Eurasians and near the root of most Native American lineages5. Similarly, we find autosomal evidence that MA-1 is basal to modern-day western Eurasians and genetically closely related to modern-day Native Americans, with no close affinity to east Asians. This suggests that populations related to contemporary western Eurasians had a more north-easterly distribution 24,000 years ago than commonly thought. Furthermore, we estimate that 14 to 38% of Native American ancestry may originate through gene flow from this ancient population. This is likely to have occurred after the divergence of Native American ancestors from east Asian ancestors, but before the diversification of Native American populations in the New World. Gene flow from the MA-1 lineage into Native American ancestors could explain why several crania from the First Americans have been reported as bearing morphological characteristics that do not resemble those of east Asians2,13. Sequencing of another south-central Siberian, Afontova Gora-2 dating to approximately 17,000 years ago14, revealed similar autosomal genetic signatures as MA-1, suggesting that the region was continuously occupied by humans throughout the Last Glacial Maximum. Our findings reveal that western Eurasian genetic signatures in modern-day Native Americans derive not only from post-Columbian admixture, as commonly thought, but also from a mixed ancestry of the First Americans.

The area of what is now the Ukraine has been the arena of large-scale demographic processes that may have left their traces in the contemporary gene pool of Ukrainians. In this study, we present new mitochondrial DNA data for 607 Ukrainians (hypervariable segment I sequences and coding region polymorphisms). To study the maternal affinities of Ukrainians at the level of separate mitochondrial haplotypes, we apply an original technique, the haplotype co-occurrence analysis. About 20% of the Ukrainian maternal gene pool is represented by lineages highly specific to Ukrainians, but is scarcely found in other populations. About 9% of Ukrainian mtDNA lineages are typical for peoples of the Volga region. We also identified minor gene pool strata (1.6-3.3%), each of which is common in Lithuanians, Estonians, Saami, Nenets, Cornish, and the populations of the North Caucasus.

Nature Communications 5: Article number: 3513 (2014); Published: 29 April 2016; Updated: 31 October 2016 This article was published without any competing financial interests statement. A revised declaration that lists potentially competing financial interests is provided below: A.D.M., M.M. and M.A.are affiliated with Bcs Biotech S.

Here we report the Simons Genome Diversity Project data set: high quality genomes from 300 individuals from 142 diverse populations. These genomes include at least 5.8 million base pairs that are not present in the human reference genome. Our analysis reveals key features of the landscape of human genome variation, including that the rate of accumulation of mutations has accelerated by about 5% in non-Africans compared to Africans since divergence. We show that the ancestors of some pairs of present-day human populations were substantially separated by 100,000 years ago, well before the archaeologically attested onset of behavioural modernity. We also demonstrate that indigenous Australians, New Guineans and Andamanese do not derive substantial ancestry from an early dispersal of modern humans; instead, their modern human ancestry is consistent with coming from the same source as that of other non-Africans., Facultad de Ciencias Naturales y Museo

High-coverage whole-genome sequence studies have so far focused on a limited number1 of geographically restricted populations2, 3, 4, 5, or been targeted at specific diseases, such as cancer6. Nevertheless, the availability of high- resolution genomic data has led to the development of new methodologies for inferring population history7, 8, 9 and refuelled the debate on the mutation rate in humans10. Here we present the Estonian Biocentre Human Genome Diversity Panel (EGDP), a dataset of 483 high-coverage human genomes from 148 populations worldwide, including 379 new genomes from 125 populations, which we group into diversity and selection sets. We analyse this dataset to refine estimates of continent-wide patterns of heterozygosity, long- and short-distance gene flow, archaic admixture, and changes in effective population size through time as well as for signals of positive or balancing selection. We find a genetic signature in present-day Papuans that suggests that at least 2% of their genome originates from an early and largely extinct expansion of anatomically modern humans (AMHs) out of Africa. Together with evidence from the western Asian fossil record11, and admixture between AMHs and Neanderthals predating the main Eurasian expansion12, our results contribute to the mounting evidence for the presence of AMHs out of Africa earlier than 75, 000 years ago.

We have analyzed Y-chromosomal variation in populations from Transoxiana, a historical region covering the southwestern part of Central Asia. We studied 780 samples from 10 regional populations of Kazakhs, Uzbeks, Turkmens, Dungans, and Karakalpaks using 35 SNP and 17 STR markers. Analysis of haplogroup frequencies using multidimensional scaling and principal component plots, supported by an analysis of molecular variance, showed that the geographic landscape of Transoxiana, despite its distinctiveness and diversity (deserts, fertile river basins, foothills and plains) had no strong influence on the genetic landscape. The main factor structuring the gene pool was the mode of subsistence: settled agriculture or nomadic pastoralism. Investigation of STR-based clusters of haplotypes and their ages revealed that cultural and demic expansions of Transoxiana were not closely connected with each other. The Arab cultural expansion introduced Islam to the region but did not leave a significant mark on the pool of paternal lineages. The Mongol expansion, in contrast, had enormous demic success, but did not impact cultural elements like language and religion. The genealogy of Muslim missionaries within the settled agricultural communities of Transoxiana was based on spiritual succession passed from teacher to disciple. However, among Transoxianan nomads, spiritual and biological succession became merged.

Y-chromosomal variation in West Asian populations has so far been studied in less detail than in the neighboring Europe. Here, we analyzed 598 Y-chromosomes from two West Asian subregions-Transcaucasia and the Armenian plateau-using 40 Y-SNPs and 17 Y-STRs and combined them with previously published data from the region. The West Asian populations fell into two clusters: upland populations from the Anatolian, Armenian and Iranian plateaus, and lowland populations from the Levant, Mesopotamia and the Arabian Peninsula. This geographic subdivision corresponds with the linguistic difference between Indo-European and Turkic speakers, on the one hand, and Semitic speakers, on the other. This subdivision could be traced back to the Neolithic epoch, when upland populations from the Anatolian and Iranian plateaus carried similar haplogroup spectra but did not overlap with lowland populations from the Levant. We also found that the initial gene pool of the Armenian motherland population has been well preserved in most groups of the Armenian Diaspora. In view of the contribution of West Asians to the autosomal gene pool of the steppe Yamnaya archaeological culture, we sequenced a large portion of the Y-chromosome in haplogroup R1b samples from present-day East European steppe populations. The ancient Yamnaya samples are located on the "eastern" R-GG400 branch of haplogroup R1b-L23, showing that the paternal descendants of the Yamnaya still live in the Pontic steppe and that the ancient Yamnaya population was not an important source of paternal lineages in present-day West Europeans.

The paternal haplogroup (hg) N is distributed from southeast Asia to eastern Europe. The demographic processes that have shaped the vast extent of this major Y chromosome lineage across numerous linguistically and autosomally divergent populations have previously been unresolved. On the basis of 94 high-coverage re-sequenced Y chromosomes, we establish and date a detailed hg N phylogeny. We evaluate geographic structure by using 16 distinguishing binary markers in 1,631 hg N Y chromosomes from a collection of 6,521 samples from 56 populations. The more southerly distributed sub-clade N4 emerged before N2a1 and N3, found mostly in the north, but the latter two display more elaborate branching patterns, indicative of regional contrasts in recent expansions. In particular, a number of prominent and well-defined clades with common N3a3'6 ancestry occur in regionally dissimilar northern Eurasian populations, indicating almost simultaneous regional diversification and expansion within the last 5,000 years. This patrilineal genetic affinity is decoupled from the associated higher degree of language diversity.

Yu.P. Altukhov suggested that heterozygosity is an indicator of the state of the gene pool. The idea and a linked concept of genetic ecological monitoring were applied to a new dataset on mtDNA variation in East European ethnic groups. Haplotype diversity (an analog of the average heterozygosity) was shown to gradually decrease northwards. Since a similar trend is known for population density, interlinked changes were assumed for a set of parameters, which were ordered to form a causative chain: latitude increases, land productivity decreases, population density decreases, effective population size decreases, isolation of subpopulations increases, genetic drift increases, and mtDNA haplotype diversity decreases. An increase in genetic drift increases the random inbreeding rate and, consequently, the genetic load. This was confirmed by a significant correlation observed between the incidence of autosomal recessive hereditary diseases and mtDNA haplotype diversity. Based on the findings, mtDNA was assumed to provide an informative genetic system for genetic ecological monitoring; e.g., analyzing the ecology-driven changes in the gene pool.

Population origins and ancestry have previously been found to be important determinants of coronary artery disease (CAD). This study investigates associations of Lebanese mitochondrial DNA lineages with CAD and studies their correlation with other populations, exploring population structures that may infer mitochondria functional associations and reveal population movements and origins. Sequencing the mitochondrial hypervariable sequence 1 (HVS-1) of 363 controls and 448 cases revealed that haplogroup W was more frequent (P = 0.013) in cases compared to controls, and was associated with increased risk of CAD (OR = 5.50, 95% CI = 1.50-35.30, P = 0.026) among Lebanese samples. Haplogroup A was only found in controls (P = 0.029). We have detected stronger geographic correlation between haplogroup W and CAD (Pearson's r = 0.316, P < 0.001) than between haplogroup A and CAD (r = 0.149, P < 0.001). HVS-1 phylogenetic network of haplogroup W shows controls are restricted to European clusters while cases belong mostly to Middle Eastern natives. The network of haplogroup A shows that the controls belong to a cluster dominated by Central Asians. Our results show evidence of a gene flow into Lebanon, creating CAD-associated population structures that are similar to those in the source populations, maintained by limited admixture, and probably encompassing variations on the nuclear and/or the mitochondrial genome that are correlated with the disease.

Population genetics successfully applies surnames as quasi-genetic markers when estimating similarity between populations and calculating the level of random inbreeding. These calculations are based on the isonymy coefficient, which assumes that every surname is monophyletic, i.e., it originated from a single common ancestor and all namesakes are therefore relatives. On the other hand, there is a general opinion that a typical Russian surname is polyphyletic: it originated multiple times and most namesakes are, therefore, not related to each other. Combined studies of Y chromosomes and surnames now allow us to address this issue. This study discusses approaches to statistical evaluation of Y chromosome haplogroup frequencies in groups of people bearing the same surname (namesakes). The proposed index of accumulated haplogroup frequency eliminates the artifactual effect of a randomly increased haplogroup frequency in namesakes by subtracting its population (expected) frequency from the observed value, while the expected frequency is calculated as the weighted average of the frequencies of this haplogroup in the populations where the surname carriers come from. From the total sample (comprising 1244 persons from 13 populations of the historical Russian area), 123 individuals carrying 14 most frequent surnames were chosen. A comparison of the haplogroup frequencies in these 14 namesake groups and in 14 respective population control groups compiled from the total sample showed that accumulation of certain Y chromosome haplogroups was nonrandom even in carriers of widespread surnames. An analysis of Y-STR haplotypes rather than Y-SNP haplogroups could provide a better insight into relationships between namesakes and will be the subject of further research.

We analyzed 40 single nucleotide polymorphism and 19 short tandem repeat Y-chromosomal markers in a large sample of 1,525 indigenous individuals from 14 populations in the Caucasus and 254 additional individuals representing potential source populations. We also employed a lexicostatistical approach to reconstruct the history of the languages of the North Caucasian family spoken by the Caucasus populations. We found a different major haplogroup to be prevalent in each of four sets of populations that occupy distinct geographic regions and belong to different linguistic branches. The haplogroup frequencies correlated with geography and, even more strongly, with language. Within haplogroups, a number of haplotype clusters were shown to be specific to individual populations and languages. The data suggested a direct origin of Caucasus male lineages from the Near East, followed by high levels of isolation, differentiation, and genetic drift in situ. Comparison of genetic and linguistic reconstructions covering the last few millennia showed striking correspondences between the topology and dates of the respective gene and language trees and with documented historical events. Overall, in the Caucasus region, unmatched levels of gene-language coevolution occurred within geographically isolated populations, probably due to its mountainous terrain.

For the first time, an analysis of five Alu insertion loci (ACE, APOA1, B65, PV92, TPA25) has been carried out in 10 Russian populations (1088 individuals) covering the whole historical area of the Russian ethnos. Depending on the locus, Russian populations exhibit similarity to their Western (European populations) or Eastern (populations of the Ural region) neighbors. Considering the frequencies of the studied Alu-insertions, the Russian gene pool exhibits low variation: average interpopulation variation (d) was 0.007, whereas on classical markers, mtDNA and Y chromosome, heterogeneity of the Russian gene pool is essentially higher (0.013, 0.033, 0.142, respectively). Therefore, on the intra-ethnic level, this set of five Alu insertions has low variation. However, a clear pattern was obtained in inter-ethnic comparison of 13 East European ethnic groups, which formed three clusters in accordance with their historical and geographical position: East Slavic, Caucasian and South Ural clusters. The obtained data confirm the efficiency of using Alu insertions for studying genetic differentiation and gene pool history of East European populations.

Human Y chromosome haplogroup structure is largely circumscribed by continental boundaries. One notable exception to this general pattern is the young haplogroup R1a that exhibits post-Glacial coalescent times and relates the paternal ancestry of more than 10% of men in a wide geographic area extending from South Asia to Central-East Europe and South Siberia. Its origin and dispersal patterns are poorly understood as no marker has yet been described that would distinguish European R1a chromosomes from Asian. Here we present frequency and haplotype diversity estimates for more than 2, 000 R1a chromosomes assessed for several newly discovered SNP markers that introduce the onset of informative R1a subdivisions by geography. Marker M434 has a low frequency and a late origin in West Asia bearing witness to recent gene flow over the Arabian Sea. Conversely, marker M458 has a significant frequency in Europe, exceeding 30% in its core area in Eastern Europe and comprising up to 70% of all M17 chromosomes present there. The diversity and frequency profiles of M458 suggest its origin during the early Holocene and a subsequent expansion likely related to a number of prehistoric cultural developments in the region. Its primary frequency and diversity distribution correlates well with some of the major Central and East European river basins where settled farming was established before its spread further eastwards. Importantly, the virtual absence of M458 chromosomes outside Europe speaks against substantial patrilineal gene flow from East Europe to Asia, including to India, at least since the mid-Holocene.

Data on the frequencies of all (50412) surnames in a total population of 849399 people have been treated by various methods of multivariate statistics (cluster analysis, multidimensional scaling, and factor analysis) to show that 22 district populations of the Central Chernozem region of Russia form a definite, ordered system of population groups. All raions (administrative districts) of Belgorod oblast (administrative region) have been grouped into four clusters corresponding to the actual geographic locations of the populations. Districts of the eastern cluster are characterized by very specific spectrum and frequencies of surnames; districts of the western cluster differ in a high proportion of Ukrainian surnames

The mean distance between birthplaces of spouses (σ, σ′), the proportion of medium migrations (k), and the effective migration pressure (Me) have considerably increased, and the linear systematic pressure coefficient (b) has decreased in the human population of the Central Chernozem region during the past 50 years. However, the local inbreeding level (a), which is determined by both an increase in the migration intensity and a decrease in the effective population size (Ne), has remained practically unchanged. A change in the regional administrative structure has affected the genetic structure of populations. In the 1950s, raions (administrative districts) of Kursk and Voronezh oblasts (regions) were similar with respect differentiation parameters, whereas the oblasts considerably differed from each other. At present, some Malecot’s isolation-by-distance parameters for the populations of the districts that were included to Belgorod oblast in 1954 are lower and similar to those for the districts that remain in Kursk and Voronezh oblasts.

Changes in the endogamy indices of district populations of the Central Chernozem region of Russia during the past 100 years were studied. The size of an elementary population in this region increased from that of a rural municipality in the mid-20th century to that of an administrative district in the late 20th century.

The frequencies and spectra of surnames have been analyzed in groups of raions (districts) of the Belgorod oblast (region) with different degrees of population subdivision. The “family name portraits” of districts with low (0.00003 < < f*r < 0.00022, \(\overline {f_r^ * } \) = 0.00015) and moderate (0.00023 < f*r < 0.00042, \(\overline {f_r^ * } \) = 0.00029) inbreeding levels are similar both to each other and to the “family name portrait” of the Belgorod oblast as a whole. Districts with high subdivision levels (0.00043 < f*r < 0.00125, \(\overline {f_r^ * } \) = 0.00072) had very distinctive surname spectra and the highest surname frequencies. Intense immigration to the Belgorod oblast significantly affects its population genetic structure, decreasing the population subdivision.

It is commonly thought that human genetic diversity in non-African populations was primarily shaped by a recent out-of-Africa dispersal. Here we present a large geographical Y chromosome study using 459 high coverage sequences, including 302 newly reported here. We date the Y chromosomal Most Recent Common Ancestor (MRCA) in Africa at 254 (95% CI 192- 307) kya and differentiation of African and non-African lineages 52-121 kya. The age estimates for major non-African founder haplogroups cluster closely in a narrow time interval at 47-52 kya, consistent with a rapid initial colonization model of Eurasia and Oceania after the out-of-Africa bottleneck. We find that the highest basal Y chromosome diversity outside Africa has been preserved in South and Southeast Asians while extant Y chromosome diversity in Europe and the Near East stems from a small number of mid-Holocene founders. In contrast to demographic reconstructions based on mtDNA, we infer a second strong bottleneck, followed by a fast recovery in Old World populations dating to the last 10 ky. We hypothesize that this bottleneck is caused by cultural changes affecting variance of reproductive success among males.

The Turkic peoples represent a diverse collection of ethnic groups defined by the Turkic languages. These groups have dispersed across a vast area, including Siberia, Northwest China, Central Asia, East Europe, the Caucasus, Anatolia, the Middle East, and Afghanistan. The origin and early dispersal history of the Turkic peoples is disputed, with candidates for their ancient homeland ranging from the Transcaspian steppe to Manchuria in Northeast Asia. Previous genetic studies have not identified a clear-cut unifying genetic signal for the Turkic peoples, which lends support for language replacement rather than demic diffusion as the model for the Turkic language’s expansion. We addressed the genetic origin of 373 individuals from 22 Turkic-speaking populations, representing their current geographic range, by analyzing genome-wide high-density genotype data. In agreement with the elite dominance model of language expansion most of the Turkic peoples studied genetically resemble their geographic neighbors. However, western Turkic peoples sampled across West Eurasia shared an excess of long chromosomal tracts that are identical by descent (IBD) with populations from present-day South Siberia and Mongolia (SSM), an area where historians center a series of early Turkic and non-Turkic steppe polities. While SSM matching IBD tracts (> 1cM) are also observed in non-Turkic populations, Turkic peoples demonstrate a higher percentage of such tracts (p-values ≤ 0.01) compared to their non-Turkic neighbors. Finally, we used the ALDER method and inferred admixture dates (~9th–17th centuries) that overlap with the Turkic migrations of the 5th–16th centuries. Thus, our results indicate historical admixture among Turkic peoples, and the recent shared ancestry with modern populations in SSM supports one of the hypothesized homelands for their nomadic Turkic and related Mongolic ancestors., Author Summary Centuries of nomadic migrations have ultimately resulted in the distribution of Turkic languages over a large area ranging from Siberia, across Central Asia to Eastern Europe and the Middle East. Despite the profound cultural impact left by these nomadic peoples, little is known about their prehistoric origins. Moreover, because contemporary Turkic speakers tend to genetically resemble their geographic neighbors, it is not clear whether their nomadic ancestors left an identifiable genetic trace. In this study, we show that Turkic-speaking peoples sampled across the Middle East, Caucasus, East Europe, and Central Asia share varying proportions of Asian ancestry that originate in a single area, southern Siberia and Mongolia. Mongolic- and Turkic-speaking populations from this area bear an unusually high number of long chromosomal tracts that are identical by descent with Turkic peoples from across west Eurasia. Admixture induced linkage disequilibrium decay across chromosomes in these populations indicates that admixture occurred during the 9th–17th centuries, in agreement with the historically recorded Turkic nomadic migrations and later Mongol expansion. Thus, our findings reveal genetic traces of recent large-scale nomadic migrations and map their source to a previously hypothesized area of Mongolia and southern Siberia.

How and when the Americas were populated remains contentious. Using ancient and modern genome-wide data, we find that the ancestors of all present-day Native Americans, including Athabascans and Amerindians, entered the Americas as a single migration wave from Siberia no earlier than 23 thousand years ago (KYA), and after no more than 8,000-year isolation period in Beringia. Following their arrival to the Americas, ancestral Native Americans diversified into two basal genetic branches around 13 KYA, one that is now dispersed across North and South America and the other is restricted to North America. Subsequent gene flow resulted in some Native Americans sharing ancestry with present-day East Asians (including Siberians) and, more distantly, Australo-Melanesians. Putative ‘Paleoamerican’ relict populations, including the historical Mexican Pericúes and South American Fuego-Patagonians, are not directly related to modern Australo-Melanesians as suggested by the Paleoamerican Model.

It has been often stated that the overall pattern of human maternal lineages in Europe is largely uniform. Yet this uniformity may also result from an insufficient depth and width of the phylogenetic analysis, in particular of the predominant western Eurasian haplogroup H that comprises nearly a half of the European mitochondrial DNA (mtDNA) pool. Making use of the coding sequence information from 267 mtDNA haplogroup (Hg) H sequences, we have analyzed 830 mtDNA genomes, from 11 European, Near and Middle Eastern, Central Asian and Altaian populations. In addition to the seven previously specified sub-haplogroups, we define fifteen novel sub-clades of Hg H present in the extant human populations of western Eurasia. The refinement of the phylogenetic resolution has allowed us to resolve a large number of homoplasies in phylogenetic trees of Hg H based on the first hypervariable segment (HVS-I) of mtDNA. As many as 50 out of 125 polymorphic positions in HVS-I were found to be mutated in more than one sub-cluster of Hg H. The phylogeographic analysis revealed that sub-Hgs H1(*), H1b, H1f, H2a, H3, H6a, H6b and H8 demonstrate distinct phylogeographic patterns. The monophyletic sub-haplogroups of Hg H provide means for further progress in the understanding of the (pre)historic movements of women in Eurasia and for the understanding of the present-day genetic diversity of western Eurasians in general.

Y-chromosomal haplogroup G1 is a minor component of the overall gene pool of South-West and Central Asia but reaches up to 80% frequency in some populations scattered within this area. We have genotyped the G1-defining marker M285 in 27 Eurasian populations (n= 5,346), analyzed 367 M285-positive samples using 17 Y-STRs, and sequenced ~11 Mb of the Y-chromosome in 20 of these samples to an average coverage of 67X. This allowed detailed phylogenetic reconstruction. We identified five branches, all with high geographical specificity: G1-L1323 in Kazakhs, the closely related G1-GG1 in Mongols, G1-GG265 in Armenians and its distant brother clade G1-GG162 in Bashkirs, and G1-GG362 in West Indians. The haplotype diversity, which decreased from West Iran to Central Asia, allows us to hypothesize that this rare haplogroup could have been carried by the expansion of Iranic speakers northwards to the Eurasian steppe and via founder effects became a predominant genetic component of some populations, including the Argyn tribe of the Kazakhs. The remarkable agreement between genetic and genealogical trees of Argyns allowed us to calibrate the molecular clock using a historical date (1405 AD) of the most recent common genealogical ancestor. The mutation rate for Y-chromosomal sequence data obtained was 0.78×10-9 per bp per year, falling within the range of published rates. The mutation rate for Y-chromosomal STRs was 0.0022 per locus per generation, very close to the so-called genealogical rate. The "clan-based" approach to estimating the mutation rate provides a third, middle way between direct farther-to-son comparisons and using archeologically known migrations, whose dates are subject to revision and of uncertain relationship to genetic events.

We sequenced the genomes of a ∼7,000-year-old farmer from Germany and eight ∼8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes1,2,3,4 with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians3, who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations’ deep relationships and show that early European farmers had ∼44% ancestry from a ‘basal Eurasian’ population that split before the diversification of other non-African lineages., Instituto Multidisciplinario de Biología Celular

The area of what is now the Ukraine has been the arena of large-scale demographic processes that may have left their traces in the contemporary gene pool of Ukrainians. In this study, we present new mitochondrial DNA data for 607 Ukrainians (hypervariable segment I sequences and coding region polymorphisms). To study the maternal affinities of Ukrainians at the level of separate mitochondrial haplotypes, we apply an original technique, the haplotype co-occurrence analysis. About 20% of the Ukrainian maternal gene pool is represented by lineages highly specific to Ukrainians, but is scarcely found in other populations. About 9% of Ukrainian mtDNA lineages are typical for peoples of the Volga region. We also identified minor gene pool strata (1.6-3.3%), each of which is common in Lithuanians, Estonians, Saami, Nenets, Cornish, and the populations of the North Caucasus.

North East Europe harbors a high diversity of cultures and languages, suggesting a complex genetic history. Archaeological, anthropological, and genetic research has revealed a series of influences from Western and Eastern Eurasia in the past. While genetic data from modern-day populations is commonly used to make inferences about their origins and past migrations, ancient DNA provides a powerful test of such hypotheses by giving a snapshot of the past genetic diversity. In order to better understand the dynamics that have shaped the gene pool of North East Europeans, we generated and analyzed 34 mitochondrial genotypes from the skeletal remains of three archaeological sites in northwest Russia. These sites were dated to the Mesolithic and the Early Metal Age (7,500 and 3,500 uncalibrated years Before Present). We applied a suite of population genetic analyses (principal component analysis, genetic distance mapping, haplotype sharing analyses) and compared past demographic models through coalescent simulations using Bayesian Serial SimCoal and Approximate Bayesian Computation. Comparisons of genetic data from ancient and modern-day populations revealed significant changes in the mitochondrial makeup of North East Europeans through time. Mesolithic foragers showed high frequencies and diversity of haplogroups U (U2e, U4, U5a), a pattern observed previously in European hunter-gatherers from Iberia to Scandinavia. In contrast, the presence of mitochondrial DNA haplogroups C, D, and Z in Early Metal Age individuals suggested discontinuity with Mesolithic hunter-gatherers and genetic influx from central/eastern Siberia. We identified remarkable genetic dissimilarities between prehistoric and modern-day North East Europeans/Saami, which suggests an important role of post-Mesolithic migrations from Western Europe and subsequent population replacement/extinctions. This work demonstrates how ancient DNA can improve our understanding of human population movements across Eurasia. It contributes to the description of the spatio-temporal distribution of mitochondrial diversity and will be of significance for future reconstructions of the history of Europeans., Author Summary The history of human populations can be retraced by studying the archaeological and anthropological record, but also by examining the current distribution of genetic markers, such as the maternally inherited mitochondrial DNA. Ancient DNA research allows the retrieval of DNA from ancient skeletal remains and contributes to the reconstruction of the human population history through the comparison of ancient and present-day genetic data. Here, we analysed the mitochondrial DNA of prehistoric remains from archaeological sites dated to 7,500 and 3,500 years Before Present. These sites are located in North East Europe, a region that displays a significant cultural and linguistic diversity today but for which no ancient human DNA was available before. We show that prehistoric hunter-gatherers of North East Europe were genetically similar to other European foragers. We also detected a prehistoric genetic input from Siberia, followed by migrations from Western Europe into North East Europe. Our research contributes to the understanding of the origins and past dynamics of human population in Europe.

International audience; Haplogroup G, together with J2 clades, has been associated with the spread of agriculture, especially in the European context. However, interpretations based on simple haplogroup frequency clines do not recognize underlying patterns of genetic diversification. Although progress has been recently made in resolving the haplogroup G phylogeny, a comprehensive survey of the geographic distribution patterns of the significant sub-clades of this haplogroup has not been conducted yet. Here we present the haplogroup frequency distribution and STR variation of 16 informative G sub-clades by evaluating 1472 haplogroup G chromosomes belonging to 98 populations ranging from Europe to Pakistan. Although no basal G-M201* chromosomes were detected in our data set, the homeland of this haplogroup has been estimated to be somewhere nearby eastern Anatolia, Armenia or western Iran, the only areas characterized by the co-presence of deep basal branches as well as the occurrence of high sub-haplogroup diversity. The P303 SNP defines the most frequent and widespread G sub-haplogroup. However, its sub-clades have more localized distribution with the U1-defined branch largely restricted to Near/Middle Eastern and the Caucasus, whereas L497 lineages essentially occur in Europe where they likely originated. In contrast, the only U1 representative in Europe is the G-M527 lineage whose distribution pattern is consistent with regions of Greek colonization. No clinal patterns were detected suggesting that the distributions are rather indicative of isolation by distance and demographic complexities.

Melé, Marta et al.-- The Genographic Consortium, The information left by recombination in our genomes can be used to make inferences on our recent evolutionary history. Specifically, the number of past recombination events in a population sample is a function of its effective population size (Ne). We have applied a method, IRiS, to detect specific past recombination events in 30 Old World populations to infer their Ne. We have found that Sub-Saharan African populations have an Ne that is ∼ 4 times greater than those of non-African populations and that outside of Africa, South Asian populations had the largest Ne. We also observe that the patterns of recombinational diversity of these populations correlate with distance out of Africa if that distance is measured along a path crossing South Arabia. No such correlation is found through a Sinai route, suggesting that anatomically modern humans first left Africa through the Bab-el-Mandeb strait rather than through present Egypt., Funding for this project was provided by National Geographic and IBM within the Genographic Project initiative and by the Spanish Ministry of Science and Innovation project BFU2010-19443 (subprogram BMC). M.M. was supported by grant AP2006-03268. Genotyping and bioinformatic services were provided respectively by CEGEN (Centro Nacional de Genotipado) and INB (National Bioinformatics Insitute), Spain.

13 páginas.-- Javed, Asif et al., We have analyzed human genetic diversity in 33 Old World populations including 23 populations obtained through Genographic Project studies. A set of 1,536 SNPs in five X chromosome regions were genotyped in 1,288 individuals (mostly males). We use a novel analysis employing subARG network construction with recombining chromosomal segments. Here, a subARG is constructed independently for each of five gene-free regions across the X chromosome, and the results are aggregated across them. For PCA, MDS and ancestry inference with STRUCTURE, the subARG is processed to obtain feature vectors of samples and pairwise distances between samples. The observed population structure, estimated from the five short X chromosomal segments, supports genome-wide frequency-based analyses: African populations show higher genetic diversity, and the general trend of shared variation is seen across the globe from Africa through Middle East, Europe, Central Asia, Southeast Asia, and East Asia in broad patterns. The recombinational analysis was also compared with established methods based on SNPs and haplotypes. For haplotypes, we also employed a fixed-length approach based on information-content optimization. Our recombinational analysis suggested a southern migration route out of Africa, and it also supports a single, rapid human expansion from Africa to East Asia through South Asia., This research is part of the Genographic Project, funded by National Geographic and IBM. Additional funding was provided by the Spanish Ministry of Science and Innovation projects BFU2007-63657, BFU2007-63171, and BFU2010-19443; MM was supported by grant AP2006-03268, Generalitat de Catalunya; OB was supported by Russian Foundation for Basic Research (grants 10-06-00451, 10-04-01603) and by the Presidium RAS Programme “Molecular and Cell Biology”.

Population origins and ancestry have previously been found to be important determinants of coronary artery disease (CAD). This study investigates associations of Lebanese mitochondrial DNA lineages with CAD and studies their correlation with other populations, exploring population structures that may infer mitochondria functional associations and reveal population movements and origins. Sequencing the mitochondrial hypervariable sequence 1 (HVS-1) of 363 controls and 448 cases revealed that haplogroup W was more frequent (P = 0.013) in cases compared to controls, and was associated with increased risk of CAD (OR = 5.50, 95% CI = 1.50-35.30, P = 0.026) among Lebanese samples. Haplogroup A was only found in controls (P = 0.029). We have detected stronger geographic correlation between haplogroup W and CAD (Pearson's r = 0.316, P0.001) than between haplogroup A and CAD (r = 0.149, P0.001). HVS-1 phylogenetic network of haplogroup W shows controls are restricted to European clusters while cases belong mostly to Middle Eastern natives. The network of haplogroup A shows that the controls belong to a cluster dominated by Central Asians. Our results show evidence of a gene flow into Lebanon, creating CAD-associated population structures that are similar to those in the source populations, maintained by limited admixture, and probably encompassing variations on the nuclear and/or the mitochondrial genome that are correlated with the disease.

Y-chromosome Haplogroup O is the dominant lineage of East Asians, comprising more than a quarter of all males on the world; however, its internal phylogeny remains insufficiently investigated. In this study, we determined the phylogenetic position of recently defined markers (L127, KL1, KL2, P164, and PK4) in the background of Haplogroup O. In the revised tree, subgroup O3a-M324 is divided into two main subclades, O3a1-L127 and O3a2-P201, covering about 20 and 35% of Han Chinese people, respectively. The marker P164 is corrected from a downstream site of M7 to upstream of M134 and parallel to M7 and M159. The marker PK4 is also relocated from downstream of M88 to upstream of M95, separating the former O2(*) into two parts. This revision evidently improved the resolving power of Y-chromosome phylogeny in East Asia.

International audience; The phylogenetic relationships of numerous branches within the core Y-chromosome haplogroup R-M207 support a West Asian origin of haplogroup R1b, its initial differentiation there followed by a rapid spread of one of its sub-clades carrying the M269 mutation to Europe. Here, we present phylogeographically resolved data for 2043 M269-derived Y-chromosomes from 118 West Asian and European populations assessed for the M412 SNP that largely separates the majority of Central and West European R1b lineages from those observed in Eastern Europe, the Circum-Uralic region, the Near East, the Caucasus and Pakistan. Within the M412 dichotomy, the major S116 sub-clade shows a frequency peak in the upper Danube basin and Paris area with declining frequency toward Italy, Iberia, Southern France and British Isles. Although this frequency pattern closely approximates the spread of the Linearbandkeramik (LBK), Neolithic culture, an advent leading to a number of pre-historic cultural developments during the past ≤10 thousand years, more complex pre-Neolithic scenarios remain possible for the L23(xM412) components in Southeast Europe and elsewhere.

Progress in the mapping of population genetic substructure provides a core source of data for the reconstruction of the demographic history of our species and for the discovery of common signals relevant to disease research: These two aspects of enquiry overlap in their empirical data content and are especially informative at continental and subcontinental levels. In the present study of the variation of the Y chromosome pool of ethnic Russians, we show that the patrilineages within the pre-Ivan the Terrible historic borders of Russia have two main distinct sources. One of these antedates the linguistic split between West and East Slavonic-speaking people and is common for the two groups; the other is genetically highlighted by the pre-eminence of haplogroup (hg) N3 and is most parsimoniously explained by extensive assimilation of (or language change in) northeastern indigenous Finno-Ugric tribes. Although hg N3 is common for both East European and Siberian Y chromosomes, other typically Siberian or Mongolian hgs (Q and C) have negligible influence within the studied Russian Y chromosome pool. The distribution of all frequent Y chromosome haplogroups (which account for 95% of the Y chromosomal spectrum in Russians) follows a similar north-south clinal pattern among autosomal markers, apparent from synthetic maps. Multidimensional scaling (MDS) plots comparing intra ethnic and interethnic variation of Y chromosome in Europe show that although well detectable, intraethnic variation signals do not cross interethnic borders, except between Poles, Ukrainians, and central-southern Russians, thereby revealing their overwhelmingly shared patrilineal ancestry.

The Saami are regarded as extreme genetic outliers among European populations. In this study, a high-resolution phylogenetic analysis of Saami genetic heritage was undertaken in a comprehensive context, through use of maternally inherited mitochondrial DNA (mtDNA) and paternally inherited Y-chromosomal variation. DNA variants present in the Saami were compared with those found in Europe and Siberia, through use of both new and previously published data from 445 Saami and 17, 096 western Eurasian and Siberian mtDNA samples, as well as 127 Saami and 2, 840 western Eurasian and Siberian Y-chromosome samples. It was shown that the "Saami motif" variant of mtDNA haplogroup U5b is present in a large area outside Scandinavia. A detailed phylogeographic analysis of one of the predominant Saami mtDNA haplogroups, U5b1b, which also includes the lineages of the "Saami motif, " was undertaken in 31 populations. The results indicate that the origin of U5b1b, as for the other predominant Saami haplogroup, V, is most likely in western, rather than eastern, Europe. Furthermore, an additional haplogroup (H1) spread among the Saami was virtually absent in 781 Samoyed and Ob-Ugric Siberians but was present in western and central European populations. The Y-chromosomal variety in the Saami is also consistent with their European ancestry. It suggests that the large genetic separation of the Saami from other Europeans is best explained by assuming that the Saami are descendants of a narrow, distinctive subset of Europeans. In particular, no evidence of a significant directional gene flow from extant aboriginal Siberian populations into the haploid gene pools of the Saami was found.

To investigate which aspects of contemporary human Y-chromosome variation in Europe are characteristic of primary colonization, late-glacial expansions from refuge areas, Neolithic dispersals, or more recent events of gene flow, we have analyzed, in detail, haplogroup I (Hg I), the only major clade of the Y phylogeny that is widespread over Europe but virtually absent elsewhere. The analysis of 1,104 Hg I Y chromosomes, which were identified in the survey of 7,574 males from 60 population samples, revealed several subclades with distinct geographic distributions. Subclade I1a accounts for most of Hg I in Scandinavia, with a rapidly decreasing frequency toward both the East European Plain and the Atlantic fringe, but microsatellite diversity reveals that France could be the source region of the early spread of both I1a and the less common I1c. Also, I1b*, which extends from the eastern Adriatic to eastern Europe and declines noticeably toward the southern Balkans and abruptly toward the periphery of northern Italy, probably diffused after the Last Glacial Maximum from a homeland in eastern Europe or the Balkans. In contrast, I1b2 most likely arose in southern France/Iberia. Similarly to the other subclades, it underwent a postglacial expansion and marked the human colonization of Sardinia approximately 9,000 years ago.

The Slavic branch of the Balto-Slavic sub- family of Indo-European languages underwent rapid divergence as a result of the spatial expansion of its speakers from Central-East Europe, in early medieval times. This expansion–mainly to East Europe and the northern Balkans–resulted in the incorporation of genetic components from numerous autochthonous populations into the Slavic gene pools. Here, we characterize genetic variation in all extant ethnic groups speaking Balto- Slavic languages by analyzing mitochondrial DNA (n = 6, 876), Y-chromosomes (n = 6, 079) and genome-wide SNP profiles (n = 296), within the context of other European populations. We also reassess the phylogeny of Slavic languages within the Balto-Slavic branch of Indo- European. We find that genetic distances among Balto-Slavic populations, based on autosomal and Y-chromosomal loci, show a high correlation (0.9) both with each other and with geography, but a slightly lower correlation (0.7) with mitochondrial DNA and linguistic affiliation. The data suggest that genetic diversity of the present-day Slavs was predominantly shaped in situ, and we detect two different substrata: ‘central-east European’ for West and East Slavs, and ‘south-east European’ for South Slavs. A pattern of distribution of segments identical by descent between groups of East- West and South Slavs suggests shared ancestry or a modest gene flow between those two groups, which might derive from the historic spread of Slavic people.

The model of the Belgorod oblast population has been used to demonstrate different effects of administrative reforms on microevolution in human populations. For the populations that formerly belonged to Kursk oblast, changes in the regional administrative structure (after which some of them remained in Kursk oblast and others were included into Belgorod oblast) have lead to an increase in the genetic distances between them. However, other populations (formerly belonging to Voronezh oblast) have become genetically closer to one another, although these populations now belong to different administrative regions (Belgorod and Voronezh oblasts).

Behar, Doron M. et al.-- The Genographic Consortium, Different lines of evidence point to the resettlement of much of western and central Europe by populations from the Franco-Cantabrian region during the Late Glacial and Postglacial periods. In this context, the study of the genetic diversity of contemporary Basques, a population located at the epicenter of the Franco-Cantabrian region, is particularly useful because they speak a non-Indo-European language that is considered to be a linguistic isolate. In contrast with genome-wide analysis and Y chromosome data, where the problem of poor time estimates remains, a new timescale has been established for the human mtDNA and makes this genome the most informative marker for studying European prehistory. Here, we aim to increase knowledge of the origins of the Basque people and, more generally, of the role of the Franco-Cantabrian refuge in the postglacial repopulation of Europe. We thus characterize the maternal ancestry of 908 Basque and non-Basque individuals from the Basque Country and immediate adjacent regions and, by sequencing 420 complete mtDNA genomes, we focused on haplogroup H. We identified six mtDNA haplogroups, H1j1, H1t1, H2a5a1, H1av1, H3c2a, and H1e1a1, which are autochthonous to the Franco-Cantabrian region and, more specifically, to Basque-speaking populations. We detected signals of the expansion of these haplogroups at ∼4,000 years before present (YBP) and estimated their separation from the pan-European gene pool at ∼8,000 YBP, antedating the Indo-European arrival to the region. Our results clearly support the hypothesis of a partial genetic continuity of contemporary Basques with the preceding Paleolithic/Mesolithic settlers of their homeland., This work was supported by the Institut Pasteur, National Geographic, and the Histoire des populations et variation linguistique dans les Pyrénées de l'Ouest project, which received funding from the Conseil Régional d'Aquitaine, the Conseil Général des Pyrénées-Atlantiques, the Conseil des Elus du Pays-Basque, and the Centre National de la Recherche Scientifique interdisciplinary program Origine de l'Homme, des Langues et du Langage. This study also benefited from the support of Department of Hematology, Centre Hospitalier de la Côte Basque, in Bayonne, and Association Sang 64.

International audience; The study of recently admixed populations provides unique tools for understanding recent population dynamics, socio-cultural factors associated with the founding of emerging populations, and the genetic basis of disease by means of admixture mapping. Historical records and recent autosomal data indicate that the South African Coloured population forms a unique highly admixed population, resulting from the encounter of different peoples from Africa, Europe, and Asia. However, little is known about the mode by which this admixed population was recently founded. Here we show, through detailed phylogeographic analyses of mitochondrial DNA and Y-chromosome variation in a large sample of South African Coloured individuals, that this population derives from at least five different parental populations (Khoisan, Bantus, Europeans, Indians, and Southeast Asians), who have differently contributed to the foundation of the South African Coloured. In addition, our analyses reveal extraordinarily unbalanced gender-specific contributions of the various population genetic components, the most striking being the massive maternal contribution of Khoisan peoples (more than 60%) and the almost negligible maternal contribution of Europeans with respect to their paternal counterparts. The overall picture of gender-biased admixture depicted in this study indicates that the modern South African Coloured population results mainly from the early encounter of European and African males with autochthonous Khoisan females of the Cape of Good Hope around 350 years ago.