The peopling of modern Bosnia-Herzegovina: Y-chromosome haplogroups in the three main ethnic groups.

The variation at 28 Y-chromosome biallelic markers was analysed in 256 males (90 Croats, 81 Serbs and 85 Bosniacs) from Bosnia-Herzegovina. An important shared feature between the three ethnic groups is the high frequency of the "Palaeolithic" European-specific haplogroup (Hg) I, a likely signature of a Balkan population re-expansion after the Last Glacial Maximum. This haplogroup is almost completely represented by the sub-haplogroup I-P37 whose frequency is, however, higher in the Croats (approximately 71%) than in Bosniacs (approximately 44%) and Serbs (approximately 31%). Other rather frequent haplogroups are E (approximately 15%) and J (approximately 7%), which are considered to have arrived from the Middle East in Neolithic and post-Neolithic times, and R-M17 (approximately 14%), which probably marked several arrivals, at different times, from eastern Eurasia. Hg E, almost exclusively represented by its subclade E-M78, is more common in the Serbs (approximately 20%) than in Bosniacs (approximately 13%) and Croats (approximately 9%), and Hg J, observed in only one Croat, encompasses approximately 9% of the Serbs and approximately 12% of the Bosniacs, where it shows its highest diversification. By contrast, Hg R-M17 displays similar frequencies in all three groups. On the whole, the three main groups of Bosnia-Herzegovina, in spite of some quantitative differences, share a large fraction of the same ancient gene pool distinctive for the Balkan area.

Y-chromosome and mtDNA polymorphisms in Iraq, a crossroad of the early human dispersal and of post-Neolithic migrations.

Analyses of mtDNA and Y-chromosome variation were performed in a sample of Iraqis, a scarcely investigated population of the "Fertile Crescent." A total of 216 mtDNAs were screened for the diagnostic RFLP markers of the main Eurasian and African haplogroups. A subset of these samples, whose HVS-I sequences were previously obtained, was also examined by high-resolution restriction analysis. The Y-chromosome variation was investigated in 139 subjects by using 17 biallelic markers and the 49a,f/Taq I system. For both uniparental systems, the large majority of the haplogroups observed in the Iraqi population are those (H, J, T, and U for the mtDNA, and J(xM172) and J-M172 for the Y chromosome) considered to have originated in the Middle East and to have later spread all over Western Eurasia. However, about 9% of the mtDNAs and 30% of the Y-chromosomes most likely represent arrivals from distant geographic regions. The different proportion of long-range genetic input observed for the mtDNA and the Y chromosome appears to indicate that events of gene flow to this area might have involved mainly males rather than females.

The 49a,f haplotype 11 is a new marker of the EU19 lineage that traces migrations from northern regions of the Black Sea.

Previous studies on human Y-chromosome polymorphisms in the European populations highlighted the high frequency of the 49a,f/TaqI haplotype 11 and of the Eu19 (M17) lineage in Eastern Europe. To better understand the origin and the evolution of the Eu19, and its relationship with 49a,f Ht11, this study surveyed 2,235 individuals (mainly from Europe and the Middle East) for the 49a,f Ht11 and for many biallelic markers defining the Eu19 lineage. As previously described, the highest frequency of Eu19 was found in Eastern Europe. All the Eu19 Y-chromosomes turned out to be 49a,f Ht11 or its derivatives, the distribution of which suggests that the Eu19/49a,f Ht11 emerged in Ukraine, probably in a Palaeolithic population. Thereafter, the spread of this lineage toward Europe, Asia, and India occurred at different waves over a few thousands years. At present this seems to indicate the influence of the Ukraine Palaeolithic groups in the gene pool of modern populations. For the first time it is possible to make inferences about the evolution of some haplotypes of the 49a,f system. In spite of its unknown molecular base, this is one of the first most informative polymorphisms of the Y chromosome.

A signal, from human mtDNA, of postglacial recolonization in Europe.

Mitochondrial HVS-I sequences from 10,365 subjects belonging to 56 populations/geographical regions of western Eurasia and northern Africa were first surveyed for the presence of the T-->C transition at nucleotide position 16298, a mutation which has previously been shown to characterize haplogroup V mtDNAs. All mtDNAs with this mutation were then screened for a number of diagnostic RFLP sites, revealing two major subsets of mtDNAs. One is haplogroup V proper, and the other has been termed "pre*V," since it predates V phylogenetically. The rather uncommon pre*V tends to be scattered throughout Europe (and northwestern Africa), whereas V attains two peaks of frequency: one situated in southwestern Europe and one in the Saami of northern Scandinavia. Geographical distributions and ages support the scenario that pre*V originated in Europe before the Last Glacial Maximum (LGM), whereas the more recently derived haplogroup V arose in a southwestern European refugium soon after the LGM. The arrival of V in eastern/central Europe, however, occurred much later, possibly with (post-)Neolithic contacts. The distribution of haplogroup V mtDNAs in modern European populations would thus, at least in part, reflect the pattern of postglacial human recolonization from that refugium, affecting even the Saami. Overall, the present study shows that the dissection of mtDNA variation into small and well-defined evolutionary units is an essential step in the identification of spatial frequency patterns. Mass screening of a few markers identified using complete mtDNA sequences promises to be an efficient strategy for inferring features of human prehistory.

The genetic legacy of Paleolithic Homo sapiens sapiens in extant Europeans: a Y chromosome perspective.

A genetic perspective of human history in Europe was derived from 22 binary markers of the nonrecombining Y chromosome (NRY). Ten lineages account for >95% of the 1007 European Y chromosomes studied. Geographic distribution and age estimates of alleles are compatible with two Paleolithic and one Neolithic migratory episode that have contributed to the modern European gene pool. A significant correlation between the NRY haplotype data and principal components based on 95 protein markers was observed, indicating the effectiveness of NRY binary polymorphisms in the characterization of human population composition and history.

MtDNA and Y chromosome polymorphisms in Hungary: inferences from the palaeolithic, neolithic and Uralic influences on the modern Hungarian gene pool.

Magyars imposed their language on Hungarians but seem not to have affected their genetic structure. To better investigate this point, we analysed some mtDNA and Y chromosome polymorphisms in a sample of the Hungarian Palóc who, for historical reasons, could have retained genetic traces of Magyars more than other groups. In addition, we examined a mixed sample from Budapest. About 100 individuals were tested for the markers defining all the European and Asian mtDNA haplogroups and about 50 individuals for some Y chromosome markers, namely the 12f2 and 49a,f/TaqI RFLPs, the YAP insertion, the microsatellites YCAIIa, YCAIIb, DYS19 and the Asian 50f2/C deletion. In the mtDNA analysis only two subjects belonged to the Asian B and M haplogroups. The Y chromosome analyses showed that the Palóc differed from the Budapest sample by the absence of YAP+ allele and by the DYS19 allele distribution; that the proto-European 49a,f Ht 15 and the neolithic 12f2-8Kb were rather uncommon in both groups; that there is a high prevalence of the 49a,f Ht 11 and the YCAII a5-b1; and that the Asian 50f2/C deletion is absent. These results suggest that the influence of Magyars on the Hungarian gene pool has been very low through both females and males and the Hungarian language could be an example of cultural dominance. Alternative explanations are discussed. An expansion centred on YAP-, 49a,f Ht 11 is revealed by the median network based on compound haplotypes. 49a,f Ht 11 could represent either a paleolithic marker of eastern Europe which underwent expansion after the last glacial period, or a marker of the more recent spread of the Yamnaia culture from southern Ukraine.

Genetic evidence of an early exit of Homo sapiens sapiens from Africa through eastern Africa.

The out-of-Africa scenario has hitherto provided little evidence for the precise route by which modern humans left Africa. Two major routes of dispersal have been hypothesized: one through North Africa into the Levant, documented by fossil remains, and one through Ethiopia along South Asia, for which little, if any, evidence exists. Mitochondrial DNA (mtDNA) can be used to trace maternal ancestry. The geographic distribution and variation of mtDNAs can be highly informative in defining potential range expansions and migration routes in the distant past. The mitochondrial haplogroup M, first regarded as an ancient marker of East-Asian origin, has been found at high frequency in India and Ethiopia, raising the question of its origin. (A haplogroup is a group of haplotypes that share some sequence variations.) Its variation and geographical distribution suggest that Asian haplogroup M separated from eastern-African haplogroup M more than 50,000 years ago. Two other variants (489C and 10873C) also support a single origin of haplogroup M in Africa. These findings, together with the virtual absence of haplogroup M in the Levant and its high frequency in the South-Arabian peninsula, render M the first genetic indicator for the hypothesized exit route from Africa through eastern Africa/western India. This was possibly the only successful early dispersal event of modern humans out of Africa.

Further characteristics of proto-European y chromosomes.

We examined a set of populations mainly from Europe but also from the Middle East and North Africa for the three Y-linked microsatellites YCAII, DYS19 (about 1300 individuals) and DYS392 (about 350 individuals). Three markers (YCAII a5-b1 Ht, DYS19-190 bp and DYS392-254 bp) show decreasing gradients of frequency from western Europe towards the Middle East which parallel that of the proto-European 49a,f/TaqI Ht 15. Indeed, a strong linkage disequilibrium between these markers and the 49a,f Ht15 is observed. We therefore suggest that the 49a,f/TaqI Ht15, YCAII a5-b1 Ht, DYS19-190 bp and DYS392-254 bp Y chromosome could represent a component of the proto-European gene pool. This European specific compound haplotype distinctively characterises western Europeans and its very high incidence in these populations (particularly in the Basques) is discussed.

Y-chromosome specific YCAII, DYS19 and YAP polymorphisms in human populations: a comparative study.

Two hypervariable Y-specific markers, the YCAII and DYS19 STRs, and the more stable Y Alu Polymorphism (YAP) have been analysed in about 1400 individuals of 21 different populations, mainly from Europe but also from the Middle East, Africa and Asia. On the basis of the frequency distributions of these three Y-markers we compare, using different statistical analyses, their power in detecting population genetic structure and in distinguishing closely related groups. The pattern of populations' genetic affinities inferred from the three markers considered altogether suggests a strong genetic structure that, with a few exceptions, broadly corresponds to the linguistic relatedness and/or geographic location of the sampled populations.

Different genetic components in the Ethiopian population, identified by mtDNA and Y-chromosome polymorphisms.

Seventy-seven Ethiopians were investigated for mtDNA and Y chromosome-specific variations, in order to (1) define the different maternal and paternal components of the Ethiopian gene pool, (2) infer the origins of these maternal and paternal lineages and estimate their relative contributions, and (3) obtain information about ancient populations living in Ethiopia. The mtDNA was studied for the RFLPs relative to the six classical enzymes (HpaI, BamHI, HaeII, MspI, AvaII, and HincII) that identify the African haplogroup L and the Caucasoid haplogroups I and T. The sample was also examined at restriction sites that define the other Caucasoid haplogroups (H, U, V, W, X, J, and K) and for the simultaneous presence of the DdeI10394 and AluI10397 sites, which defines the Asian haplogroup M. Four polymorphic systems were examined on the Y chromosome: the TaqI/12f2 and the 49a,f RFLPs, the Y Alu polymorphic element (DYS287), and the sY81-A/G (DYS271) polymorphism. For comparison, the last two Y polymorphisms were also examined in 87 Senegalese previously classified for the two TaqI RFLPs. Results from these markers led to the hypothesis that the Ethiopian population (1) experienced Caucasoid gene flow mainly through males, (2) contains African components ascribable to Bantu migrations and to an in situ differentiation process from an ancestral African gene pool, and (3) exhibits some Y-chromosome affinities with the Tsumkwe San (a very ancient African group). Our finding of a high (20%) frequency of the "Asian" DdeI10394AluI10397 (++) mtDNA haplotype in Ethiopia is discussed in terms of the "out of Africa" model.

Human genetic affinities for Y-chromosome P49a,f/TaqI haplotypes show strong correspondence with linguistics.

Numerous population samples from around the world have been tested for Y chromosome-specific p49a,f/TaqI restriction polymorphisms. Here we review the literature as well as unpublished data on Y-chromosome p49a,f/TaqI haplotypes and provide a new nomenclature unifying the notations used by different laboratories. We use this large data set to study worldwide genetic variability of human populations for this paternally transmitted chromosome segment. We observe, for the Y chromosome, an important level of population genetics structure among human populations (FST = .230, P < .001), mainly due to genetic differences among distinct linguistic groups of populations (FCT = .246, P < .001). A multivariate analysis based on genetic distances between populations shows that human population structure inferred from the Y chromosome corresponds broadly to language families (r = .567, P < .001), in agreement with autosomal and mitochondrial data. Times of divergence of linguistic families, estimated from their internal level of genetic differentiation, are fairly concordant with current archaeological and linguistic hypotheses. Variability of the p49a,f/TaqI polymorphic marker is also significantly correlated with the geographic location of the populations (r = .613, P < .001), reflecting the fact that distinct linguistic groups generally also occupy distinct geographic areas. Comparison of Y-chromosome and mtDNA RFLPs in a restricted set of populations shows a globally high level of congruence, but it also allows identification of unequal maternal and paternal contributions to the gene pool of several populations.

Pre-Caucasoid and Caucasoid genetic features of the Indian population, revealed by mtDNA polymorphisms.

About 70 individuals from Punjab were examined for some mtDNA polymorphisms, namely, the RFLPs of the six classical enzymes (HpaI, BamHI, HaeII, MspI, AvaII, and Hin-cII) and for the sites AluI(7,025), DdeI(10,394), and AluI(10,397). The AluI(7,025) polymorphic site was also investigated in 96 Indians from Uttar Pradesh and Andhra Pradesh and in 163 Mediterranean Caucasoids. Moreover, 30 Indian DdeI(10,394)Alu(10,397) (++) mtDNAs were typed by the "high-resolution restriction analysis" with 14 endonucleases to estimate their divergence time. The results obtained are the following: (1) The RFLPs analysis has displayed some Caucasoid types as in Indians of Uttar Pradesh; (2) the AluI(7,025) (-) allele, which defines the most frequent Caucasoid-specific lineage (haplogroup H), ranges from 18% to 45% in the Mediterranean Caucasoids, whereas it has shown low frequencies in Punjab (6.0%) and in Uttar Pradesh (1.8%) and was not found in Andhra Pradesh; (3) the DdeI(lO,394)AluI(10,397) (+ +) haplotype, which although previously was considered an East Asian marker (haplogroup M) and was found very frequently in India, is also frequent in Punjab (27%); this frequency is, however, much lower than in Uttar Pradesh (49%) and in Andhra Pradesh (74%), and a gradient decreasing from south to north is therefore observed; (4) the divergence time of the Indian DdeI(10,394)AluI(10,397) (++) mtDNAs has been estimated to be 30,250-60,500 years, a value that is compatible with that of the homologous East Asian lineage. These results strongly support the hypothesis that the DdeI(10,394)AluI(10,397) (++) haplotype predated the Indo-European invasion and probably the split between proto-Indians and proto-Orientals. Its frequency cline well reflects the major influence of Indo-Europeans in the north and in the center of India.

mtDNA provides the first known marker distinguishing proto-Indians from the other Caucasoids; it probably predates the diversification between Indians and Orientals.

The concomitant presence of the two sites Ddel at 10,394 and Alul at 10,397 has been considered an East-Asian marker of ancient origin (it was also observed in Australians, Melanesians and Native Americans). Unexpectedly, it was found in more than 50% of Indians (133 Hindus and 30 Tribals) who had shown Caucasoid characteristics not only at nuclear DNA but also at mtDNA level. It can therefore no longer be considered an exclusively East-Asian mtDNA feature. The analysis of more than 200 Caucasoids, mainly from the Mediterranean basin, showed that it is only sporadically present in these people. Thus it represents the first known marker which distinguishes Indians from the other Caucasoids. The lack of this marker in Indian mtDNA molecules carrying Caucasoid characteristics suggests that it predates the invasion of India by speakers of an Indo-European language and, if it is valid to extrapolate from Near Eastern data, the arrival in India of the farmers who spread the Dravidian language. If this polymorphism had a common origin in both Orientals and Indians, it should also predate the diversification between ancient Indians and Mongoloids.

Global patterns of linkage disequilibrium at the CD4 locus and modern human origins.

Haplotypes consisting of alleles at a short tandem repeat polymorphism (STRP) and an Alu deletion polymorphism at the CD4 locus on chromosome 12 were analyzed in more than 1600 individuals sampled from 42 geographically dispersed populations (13 African, 2 Middle Eastern, 7 European, 9 Asian, 3 Pacific, and 8 Amerindian). Sub-Saharan African populations had more haplotypes and exhibited more variability in frequencies of haplotypes than the Northeast African or non-African populations. The Alu deletion was nearly always associated with a single STRP allele in non-African and Northeast African populations but was associated with a wide range of STRP alleles in the sub-Saharan African populations. This global pattern of haplotype variation and linkage disequilibrium suggests a common and recent African origin for all non-African human populations.

Analysis of mtDNA variation in African populations reveals the most ancient of all human continent-specific haplogroups.

mtDNA sequence variation was examined in 140 Africans, including Pygmies from Zaire and Central African Republic (C.A.R.) and Mandenkalu, Wolof, and Pular from Senegal. More than 76% of the African mtDNAs (100% of the Pygmies and 67.3% of the Senegalese) formed one major mtDNA cluster (haplogroup L) defined by an African-specific HpaI site gain at nucleotide pair (np) 3592. Additional mutations subdivided haplogroup L into two subhaplogroups, each encompassing both Pygmy and Senegalese mtDNAs. A novel 12-bp homoplasmic insertion in the intergenic region between tRNA(Tyr) and cytochrome oxidase I (COI) genes was also observed in 17.6% of the Pygmies from C.A.R. This insertion is one of the largest observed in human mtDNAs. Another 25% of the Pygmy mtDNAs harbored a 9-bp deletion between the cytochrome oxidase II (COII) and tRNA(Lys) genes, a length polymorphism previously reported in non-African populations. In addition to haplogroup L, other haplogroups were observed in the Senegalese. These haplogroups were more similar to those observed in Europeans and Asians than to haplogroup L mtDNAs, suggesting that the African mtDNAs without the HpaI np 3592 site could be the ancestral types from which European and Asian mtDNAs were derived. Comparison of the intrapopulation sequence divergence in African and non-African populations confirms that African populations exhibit the largest extent of mtDNA variation, a result that further supports the hypothesis that Africans represent the most ancient human group and that all modern humans have a common and recent African origin. The age of the total African variation was estimated to be 101,000-133,000 years before present (YBP), while the age of haplogroup L was estimated at 98,000-130,000 YBP. These values substantially exceed the ages of all Asian- and European-specific mtDNA haplogroups.

MtDNA polymorphisms in a sample of Czechoslovaks and in two groups of Italians.

Mitochondrial DNA (mtDNA) variation was investigated in a group of 185 unrelated individuals (64 Czechoslovaks, 99 Northern and 28 Central Italians) using total blood DNA and the six restriction enzymes HpaI, BamHI, HaeII, MspI, AvaII and HincII. Among the 25 patterns (morphs) found, two morphs for HaeII, one for MspI and one for AvaII were new and each was represented by a single individual from Northern Italy. They account for four of the five new types encountered in this survey, being the fifth type characterized by the presence of the very rare morph HaeII-13. The populations analysed confirm the Caucasoid characteristics of certain polymorphisms. A review of the European data available so far is reported.

COII/tRNA(Lys) intergenic 9-bp deletion and other mtDNA markers clearly reveal that the Tharus (southern Nepal) have Oriental affinities.

We searched for the East Asian mtDNA 9-bp deletion in the intergenic COII/tRNA(Lys) region in a sample of 107 Tharus (50 from central Terai and 57 from eastern Terai), a population whose anthropological origin has yet to be completely clarified. The deletion, detected by electrophoresis of the PCR-amplified nt 7392-8628 mtDNA fragment after digestion with HaeIII, was found in about 8% of both Tharu groups but was found in none of the 76 Hindus who were examined as a non-Oriental neighboring control population. A complete triplication of the 9-bp unit, the second case so far reported, was also observed in one eastern Tharu. All the mtDNAs with the deletion, and that with the triplication, were further characterized (by PCR amplification of the relevant mtDNA fragments and their digestion with the appropriate enzymes) to locate them in the Ballinger et al. phylogeny of East Asian mtDNA haplotypes. The deletion was found to be associated with four different haplotypes, two of which are reported for the first time. One of the deletions and especially the triplication could be best explained by the assumption of novel length-change events. Ballinger's classification of East Asian mtDNA haplotypes is mainly based on the phenotypes for the DdeI site at nt 10394 and the AluI site at nt 10397. Analysis of the entire Tharu sample revealed that more than 70% of the Tharus have both sites, the association of which has been suggested as an ancient East Asian peculiarity. These results conclusively indicate that the Tharus have a predominantly maternal Oriental ancestry. Moreover, they show at least one and perhaps two further distinct length mutations, and this suggests that the examined region is a hot spot of rearrangements.

The common, Near-Eastern origin of Ashkenazi and Sephardi Jews supported by Y-chromosome similarity.

About 80 Sephardim, 80 Ashkenazim and 100 Czechoslovaks were examined for the Y-specific RFLPs revealed by the probes p12f2 and p49a,f on TaqI DNA digests. The aim of the study was to investigate the origin of the Ashkenazi gene pool through the analysis of markers which, having an exclusively holoandric transmission, are useful to estimate paternal gene flow. The comparison of the two groups of Jews with each other and with Czechoslovaks (which have been taken as a representative source of foreign Y-chromosomes for Ashkenazim) shows a great similarity between Sephardim and Ashkenazim who are very different from Czechoslovaks. On the other hand both groups of Jews appear to be closely related to Lebanese. A preliminary evaluation suggests that the contribution of foreign males to the Ashkenazi gene pool has been very low (1% or less per generation).

MtDNA polymorphisms among Tharus of eastern Terai (Nepal).

Tharus--a population of Terai (a region with a severe malarial morbidity in the past)--can be subdivided into three main groups: Western, Central and Southern Tharus. They have usually been considered a Mongoloid population and this has been further substantiated by mtDNA findings on Central Tharus. Studies on the distribution of malaria-related genes have shown an extremely high frequency (0.8) of the alpha-thal gene among Western and Central Tharus. This frequency, however, unexpectedly turned out to be only 0.04 in a sample of Eastern Tharus. This raised doubts on the common notion that Tharus are a single anthropological entity. In the present investigation mtDNA markers were studied in the same sample of Eastern Tharus previously examined for the alpha-thal gene. The findings were: 1. the same three features which confirmed the classification of Central Tharus as Mongoloids (i.e., the common occurrence of HpaI-1/HincII-1 and HaeII-5 morphs, and the lack of BamHI polymorphism) were also present in this sample. Since the only neighbouring population accessible to Tharus, until recently, has been Hindu (Caucasoids), this result strongly supports the notion that Tharus are indeed a single anthropological entity; 2. two statistically significant differences between Eastern and Central Tharus--namely, a much higher HaeII morph 5 frequency among Central Tharus, and the absence in the same group of the mutation at 15.487 bp (very common among Eastern Tharus)--together with the results on alpha-tal gene, suggested that Tharu subgroups underwent an effective reproductive isolation.