Y-Chromosomal DNA Variation in Pakistan

Eighteen binary polymorphisms and 16 multiallelic, short-tandem-repeat (STR) loci from the nonrecombining portion of the human Y chromosome were typed in 718 male subjects belonging to 12 ethnic groups of Pakistan. These identified 11 stable haplogroups and 503 combination binary marker/STR haplotypes. Haplogroup frequencies were generally similar to those in neighboring geographical areas, and the Pakistani populations speaking a language isolate (the Burushos), a Dravidian language (the Brahui), or a Sino-Tibetan language (the Balti) resembled the Indo-European-speaking majority. Nevertheless, median-joining networks of haplotypes revealed considerable substructuring of Y variation within Pakistan, with many populations showing distinct clusters of haplotypes. These patterns can be accounted for by a common pool of Y lineages, with substantial isolation between populations and drift in the smaller ones. Few comparative genetic or historical data are available for most populations, but the results can be compared with oral traditions about origins. The Y data support the well-established origin of the Parsis in Iran, the suggested descent of the Hazaras from Genghis Khan's army, and the origin of the Negroid Makrani in Africa, but do not support traditions of Tibetan, Syrian, Greek, or Jewish origins for other populations.

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Polarity and Temporality of High-Resolution Y-Chromosome Distributions in India Identify Both Indigenous and Exogenous Expansions and Reveal Minor Genetic Influence of Central Asian Pastoralists

Although considerable cultural impact on social hierarchy and language in South Asia is attributable to the arrival of nomadic Central Asian pastoralists, genetic data (mitochondrial and Y chromosomal) have yielded dramatically conflicting inferences on the genetic origins of tribes and castes of South Asia. We sought to resolve this conflict, using high-resolution data on 69 informative Y-chromosome binary markers and 10 microsatellite markers from a large set of geographically, socially, and linguistically representative ethnic groups of South Asia. We found that the influence of Central Asia on the pre-existing gene pool was minor. The ages of accumulated microsatellite variation in the majority of Indian haplogroups exceed 10,000–15,000 years, which attests to the antiquity of regional differentiation. Therefore, our data do not support models that invoke a pronounced recent genetic input from Central Asia to explain the observed genetic variation in South Asia. R1a1 and R2 haplogroups indicate demographic complexity that is inconsistent with a recent single history. Associated microsatellite analyses of the high-frequency R1a1 haplogroup chromosomes indicate independent recent histories of the Indus Valley and the peninsular Indian region. Our data are also more consistent with a peninsular origin of Dravidian speakers than a source with proximity to the Indus and with significant genetic input resulting from demic diffusion associated with agriculture. Our results underscore the importance of marker ascertainment for distinguishing phylogenetic terminal branches from basal nodes when attributing ancestral composition and temporality to either indigenous or exogenous sources. Our reappraisal indicates that pre-Holocene and Holocene-era — not Indo-European — expansions have shaped the distinctive South Asian Y-chromosome landscape.

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A Diffusion Wave out of Africa

This paper proposes that the worldwide transition to an anatomically modern human form was caused by the diffusive spread from Africa of a genotype — a coadapted combination of novel genes — carrying a complex genetic advantage. It is suggested that the movement out of Africa was not a migration but a "diffusion wave" — a continuous expansion of modern populations by small random movements, hybridization, and natural selection favoring the modern genotype. It is proposed that the modern genotype arose in Africa by a shifting-balance process and spread because it was globally advantageous. It is shown that the genotype could have spread by directionally random demic diffusion, but only under conditions involving a low rate of interdeme admixture ("interbreeding") and strong selection. This mechanism is investigated using a quantitative model that suggests explanations for many puzzling aspects of the genetic, fossil, and archaeological data on modern human origins. The data indicate significant genetic assimilation from archaic human populations into modern ones. A morphological advantage of the modern phenotype — possibly reducing childbirth mortality — is proposed as the cause of the transition. The evidence of this and previous human "revolutions" suggests that the shifting-balance process, proposed by Sewall Wright, was particularly important in human evolution — possibly because human populations had a small-deme social structure with low interbreeding rates that allowed it to operate. This may explain the relative uniqueness of human evolution.

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On the Diffusion-Wave Model for the Spread of Modern Humans

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Mixed Signals of Expansions Refute an Exclusively African Descent for Modern Humans

Ten years ago evidence from genetics gave strong support to the “recent Africa origin” (rao) view of the evolution of modern humans, but subsequent large bodies of data not only have failed to support the rao model, they do not support any simple model of human demographic history. In this paper we study a process in which modern humans originate in Africa, then spread across the world by local demic diffusion, hybridization, and natural selection which fixes an advantageous gene combination characterizing anatomical modernity. Numerical simulations of this process replicate many of the seemingly contradictory features of the genetic data and suggests that as much as 80% of nuclear loci have assimilated genetic material from non-African archaic humans.

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Population History and Natural Selection Shape Patterns of Genetic Variation in 132 Genes

Identifying regions of the human genome that have been targets of natural selection will provide important insights into human evolutionary history and may facilitate the identification of complex disease genes. Although the signature that natural selection imparts on DNA sequence variation is difficult to disentangle from the effects of neutral processes such as population demographic history, selective and demographic forces can be distinguished by analyzing multiple loci dispersed throughout the genome. We studied the molecular evolution of 132 genes by comprehensively resequencing them in 24 African-Americans and 23 European-Americans. We developed a rigorous computational approach for taking into account multiple hypothesis tests and demographic history and found that while many apparent selective events can instead be explained by demography, there is also strong evidence for positive or balancing selection at eight genes in the European-American population, but none in the African-American population. Our results suggest that the migration of modern humans out of Africa into new environments was accompanied by genetic adaptations to emergent selective forces. In addition, a region containing four contiguous genes on Chromosome 7 showed striking evidence of a recent selective sweep in European-Americans. More generally, our results have important implications for mapping genes underlying complex human diseases.

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Genomics refutes an exclusively African origin of humans

Ten years ago, evidence from genetics gave strong support to the "recent Africa origin" view of the evolution of modern humans, which posits that Homo sapiens arose as a new species in Africa and subsequently spread, leading to the extinction of other archaic human species. Subsequent data from the nuclear genome not only fail to support this model, they do not support any simple model of human demographic history. In this paper, we study a process in which the modern human phenotype originates in Africa and then advances across the world by local demic diffusion, hybridization, and natural selection. While the multiregional model of human origins posits a number of independent single locus selective sweeps, and the "out of Africa" model posits a sweep of a new species, we study the intermediate case of a phenotypic sweep. Numerical simulations of this process replicate many of the seemingly contradictory features of the genetic data, and suggest that as much as 80% of nuclear loci have assimilated genetic material from non-African archaic humans.

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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 inmind that linking phylogeography of various haplogroups with known historic and prehistoric scenarios should be cautiously performed.

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Gene Pool Structure of Eastern Ukrainians as Inferred from the Y-Chromosome Haplogroups

Y chromosomes from representative sample of Eastern Ukrainians (94 individuals) were analyzed for composition and frequencies of haplogroups, defined by 11 biallelic loci located in non-recombining part of the chromosome (SRY1532, YAP, 92R7, DYF155S2, 12f2, Tat, M9, M17, M25, M89, and M56). In the Ukrainian gene pool six haplogroups were revealed: E, F (including G and I), J, N3, P, and R1a1. These haplogroups were earlier detected in a study of Y-chromosome diversity on the territory of Europe as a whole. The major haplogroup in the Ukrainian gene pool, haplogroup R1a1 (earlier designated HG3), accounted for about 44% of all Y chromosomes in the sample examined. This haplogroup is thought to mark the migration patterns of the early Indo-Europeans and is associated with the distribution of the Kurgan archaeological culture. The second major haplogroup is haplogroup F (21.3%), which is a combination of the lineages differing by the time of appearance. Haplogroup P found with the frequency of 9.6%, represents the genetic contribution of the population originating from the ancient autochthonous population of Europe. Haplogroups J and E (11.7 and 4.2%, respectively) mark the migration patterns of the Middle-Eastern agriculturists during the Neolithic. The presence of the N3 lineage (9.6%) is likely explained by a contribution of the assimilated Finno–Ugric tribes. The data on the composition and frequencies of Y-chromosome haplogroups in the sample studied substantially supplement the existing picture of the male lineage distribution in the Eastern Slav population.

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High-Resolution Phylogenetic Analysis of Southeastern Europe (SEE) Traces Major Episodes of Paternal Gene Flow Among Slavic Populations

The extent and nature of SEE paternal genetic contribution to European genetic landscape was explored based on a high-resolution Y chromosome analysis involving 681 males from 7 populations in the region. Paternal lineages present in SEE were compared with previously published data from 81 western Eurasian populations and 5,017 Y chromosome samples. The finding that five major haplogroups (E3b1, I1b* (xM26), J2, R1a, R1b) comprise more than 70% of SEE total genetic variation is consistent with the typical European Y chromosome gene pool. However, distribution of major Y chromosomal lineages and estimated expansion signals clarify the specific role of this region in structuring of European, and particularly, Slavic paternal genetic heritage. Contemporary Slavic paternal gene pool, mostly characterized by the predominance of R1a and I1b* (xM26), and scarcity of E3b1 lineages, is a result of two major prehistoric gene flows with opposite directions: the post-LGM R1a expansion from east to west, the YD-Holocene I1b* (xM26) diffusion out of SEE in addition to subsequent R1a and I1b* (xM26) putative gene flows between eastern and southeastern Europe and a rather weak extent of E3b1 diffusion towards regions nowadays occupied by Slavic speaking populations.

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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 (~71%) than in Bosniacs (~44%) and Serbs (~31%). Other rather frequent haplogroups are E (~15%) and J (~7%), which are considered to have arrived from the Middle East in Neolithic and post-Neolithic times, and R-M17 (~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 (~20%) than in Bosniacs (~13%) and Croats (~9%), and Hg J, observed in only one Croat, encompasses ~9% of the Serbs and ~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.

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Y-chromosome variation and Irish origins

Ireland’s position on the western edge of Europe suggests that the genetics of its population should have been relatively undisturbed by the demographic movements that have shaped variation on the mainland. We have typed 221 Y chromosomes from Irish males for seven (slowly evolving) biallelic and six (quickly evolving) simple tandem-repeat markers. When these samples are partitioned by surname, we find significant differences in genetic frequency between those of Irish Gaelic and of foreign origin, and also between those of eastern and western Irish origin. Connaught, the westernmost Irish province, lies at the geographical and genetic extreme of a Europe-wide cline.

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The mutation spectrum of hyperphenylalaninaemia in the Republic of Ireland: the population history of the Irish revisited

Phenylketonuric and hyperphenylalaninaemic patients in the population of the Republic of Ireland were screened for mutations at the human phenylalanine hydroxylase (PAH) locus. A composite data set for the island of Ireland was generated by merging the findings of this study with extant data for Northern Ireland. Analysis of this data on the basis of the four historic provinces (Munster, Leinster, Connacht and Ulster) revealed genetic diversity that is informative in terms of demographic forces that shaped the Irish population. R408W, the predominant Irish PAH mutation associated with haplotype 1.8, reached its highest relative frequency in the most westerly province, Connacht. This suggests that the gradient of R408W-1.8 observed across north-western Europe continues into Ireland and peaks in Connacht. Spatial autocorrelation analysis demonstrated that the gradient is consistent with a localised cline of R408W-1.8 likely to have been established by human migration. This and parallel allele frequency clines may represent the genetic traces of the Palaeolithic colonisation of Europe, a pattern not substantially altered in north-western Europe by subsequent Neolithic migrations. An analysis of mutant allele distributions in Ulster, Scotland and the rest of Ireland confirmed that Ulster has been a zone of considerable admixture between the Irish and Scottish populations, indicating a proportion of Scottish admixture in Ulster approaching 46%. Mutations primarily associated with Scandinavia accounted for 6.1% of mutations overall, illustrating the influence of Viking incursions on Irish population history.

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Genetic Diversity Within the R408W Phenylketonuria Mutation Lineages in Europe

The R408W phenylketonuria mutation in Europe has arisen by recurrent mutation in the human phenylalanine hydroxylase (PAH) locus and is associated with two major PAH haplotypes. R408W-2.3 exhibits a west-to-east cline of relative frequency reaching its maximum in the Balto–Slavic region, while R408W-1.8 exhibits an east-to-west cline peaking in Connacht, the most westerly province of Ireland. Spatial autocorrelation analysis has demonstrated that the R408W-2.3 cline, like that of R408W-1.8, is consistent with a pattern likely to have been established by human dispersal. Genetic diversity within wild-type and R408W chromosomes in Europe was assessed through variable number tandem repeat (VNTR) nucleotide sequence variation and tetranucleotide short tandem repeat (STR) allelic associations. Wild-type VNTR-8 chromosomes exhibited two major cassette sequence organizations: (a1)5-b3-b2-c1 and (a1)5-b5-b2-c1. R408W-1.8 was predominantly associated with (a1)5-b5-b2-c1. Both wild-type VNTR-3 and R408W-2.3 chromosomes exhibited a single invariant cassette sequence organization, a2-b2-c1. STR allele distributions associated with the cassette variants were consistent with greater diversity in the wild-type VNTR-8 lineage and were suggestive of different levels of diversity between R408W-1.8 and R408W-2.3. The finding of greater genetic diversity within the wild-type VNTR-8 lineage compared to VNTR-3 suggests that VNTR-8 may be older within the European population. However, in the absence of a more extensive STR data-set, no such conclusions are possible for the respective R408W mutant lineages.

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The Longue Duree of Genetic Ancestry: Multiple Genetic Marker Systems and Celtic Origins on the Atlantic Facade of Europe

Celtic languages are now spoken only on the Atlantic facade of Europe, mainly in Britain and Ireland, but were spoken more widely in western and central Europe until the collapse of the Roman Empire in the first millennium A.D. It has been common to couple archaeological evidence for the expansion of Iron Age elites in central Europe with the dispersal of these languages and of Celtic ethnicity and to posit a central European “homeland” for the Celtic peoples. More recently, however, archaeologists have questioned this “migrationist” view of Celtic ethnogenesis. The proposition of a central European ancestry should be testable by examining the distribution of genetic markers; however, although Y-chromosome patterns in Atlantic Europe show little evidence of central European influence, there has hitherto been insufficient data to confirm this by use of mitochondrial DNA (mtDNA). Here, we present both new mtDNA data from Ireland and a novel analysis of a greatly enlarged European mtDNA database. We show that mtDNA lineages, when analyzed in sufficiently large numbers, display patterns significantly similar to a large fraction of both Y-chromosome and autosomal variation. These multiple genetic marker systems indicate a shared ancestry throughout the Atlantic zone, from northern Iberia to western Scandinavia, that dates back to the end of the last Ice Age.

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A Y-Chromosome Signature of Hegemony in Gaelic Ireland

Seventeen-marker simple tandem repeat genetic analysis of Irish Y chromosomes reveals a previously unnoted modal haplotype that peaks in frequency in the northwestern part of the island. It shows a significant association with surnames purported to have descended from the most important and enduring dynasty of early medieval Ireland, the Uí Néill. This suggests that such phylogenetic predominance is a biological record of past hegemony and supports the veracity of semimythological early genealogies. The fact that about one in five males sampled in northwestern Ireland is likely a patrilineal descendent of a single early medieval ancestor is a powerful illustration of the potential link between prolificacy and power and of how Y-chromosome phylogeography can be influenced by social selection.

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Patterns of male-specific inter-population divergence in Europe, West Asia and North Africa

We typed 1801 males from 55 locations for the Y-specific binary markers YAP, DYZ3, SRY₁₀₈₃₁ and the (CA)n microsatellites YCAII and DYS413. Phylogenetic relationships of chromosomes with the same binary haplotype were condensed in seven large one-step networks, which accounted for 95% of all chromosomes. Their coalescence ages were estimated based on microsatellite diversity. The three largest and oldest networks undergo sharp frequency changes in three areas. The more recent network 3.1A clearly discriminates between Western and Eastern European populations. Pairwise Fst showed an overall increment with increasing geographic distance but with a slope greatly reduced when compared to previous reports. By sectioning the entire data set according to geographic and linguistic criteria, we found higher Fst-on-distance slopes within Europe than in West Asia or across the two continents.

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Phylogeographic Analysis of Haplogroup E3b (E-M215) Y Chromosomes Reveals Multiple Migratory Events Within and Out Of Africa

We explored the phylogeography of human Y-chromosomal haplogroup E3b by analyzing 3,401 individuals from five continents. Our data refine the phylogeny of the entire haplogroup, which appears as a collection of lineages with very different evolutionary histories, and reveal signatures of several distinct processes of migrations and/or recurrent gene flow that occurred in Africa and western Eurasia over the past 25,000 years. In Europe, the overall frequency pattern of haplogroup E-M78 does not support the hypothesis of a uniform spread of people from a single parental Near Eastern population. The distribution of E-M81 chromosomes in Africa closely matches the present area of distribution of Berber-speaking populations on the continent, suggesting a close haplogroup–ethnic group parallelism. E-M34 chromosomes were more likely introduced in Ethiopia from the Near East. In conclusion, the present study shows that earlier work based on fewer Y-chromosome markers led to rather simple historical interpretations and highlights the fact that many population-genetic analyses are not robust to a poorly resolved phylogeny.

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YAP, signature of an African–Middle Eastern migration into northern India

YAP, an Alu insertion polymorphism found on human Y-chromosome is present in two lineages worldwide, corresponding to M145/M203/SRY4064 (haplogroup E) and M145/M203/M174 (haplogroup D) polymorphisms respectively. First lineage belonging to haplogroup D is specific to Japan and other Southeast Asian populations, while haplogroup E is confined to Sub-Saharan African, Middle Eastern and Southern European populations. In the present study, 1021 Y-chromosomes belonging to nine different populations of North India were analysed for YAP insertion and four other single nucleotide polymorphisms (SNPs) to delineate the two lineages. Out of nine populations only one, i.e. Shiya Muslims revealed presence of YAP element at a frequency of 11%. Further analysis based on four additional SNPs revealed that all the YAP+ve samples could be categorized under African/Middle East-specific haplogroup E lineage. Interestingly, Sunni Muslims who historically have the same origin, i.e. from the Middle east showed a complete lack of YAP+ve lineage similar to other castes. We hypothesize that unlike Sunnis, Shiya Muslims due to their lesser number and less admixture with other caste groups of India, still carry the ancestral YAP+ve lineage, which in all probabilities is one of the founder haplogroups. All Middle Eastern populations show the presence of this lineage in almost similar frequency. Our study shows the presence of YAP+ve lineage in North Indian populations, reflecting an African/Middle Eastern migration into North India.

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Phylogenetic Analysis of Major African Genotype (Af2) of JC Virus: Implications for Origin and Dispersals of Modern Africans

Both mtDNA and the Y chromosome have been used to investigate how modern humans dispersed within and out of Africa. This issue can also be studied using the JC virus (JCV) genotype, a novel marker with which to trace human migrations. Africa is mainly occupied by two genotypes of JCV, designated Af1 and Af2. Af1 is localized to central/western Africa, while Af2 is spread throughout Africa and in neighboring areas of Asia and Europe. It was recently suggested that Af1 represents the ancestral type of JCV, which agrees with the African origin of modern humans. To better understand the origin of modern Africans, we examined the phylogenetic relationships among Af2 isolates worldwide. A neighbor-joining phylogenetic tree was constructed based on the complete JCV DNA sequences of 51 Af2 isolates from Africa and neighboring areas. According to the resultant tree, Af2 isolates diverged into two major clusters, designated Af2-a and -b, with high bootstrap probabilities. Af2-a contained isolates mainly from South Africa, while Af2-b contained those from the other parts of Africa and neighboring regions of Asia and Europe. These findings suggest that Af2-carrying Africans diverged into two groups, one carrying Af2-a and the other carrying Af2-b; and that the former moved to southern Africa, while the latter dispersed throughout Africa and to neighboring regions of Asia and Europe. The present findings are discussed with reference to relevant findings in genetic and linguistic studies.

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