The impact of Converso Jews on the genomes of modern Latin Americans.

Modern day Latin America resulted from the encounter of Europeans with the indigenous peoples of the Americas in 1492, followed by waves of migration from Europe and Africa. As a result, the genomic structure of present day Latin Americans was determined both by the genetic structure of the founding populations and the numbers of migrants from these different populations. Here, we analyzed DNA collected from two well-established communities in Colorado (33 unrelated individuals) and Ecuador (20 unrelated individuals) with a measurable prevalence of the BRCA1 c.185delAG and the GHR c.E180 mutations, respectively, using Affymetrix Genome-wide Human SNP 6.0 arrays to identify their ancestry. These mutations are thought to have been brought to these communities by Sephardic Jewish progenitors. Principal component analysis and clustering methods were employed to determine the genome-wide patterns of continental ancestry within both populations using single nucleotide polymorphisms, complemented by determination of Y-chromosomal and mitochondrial DNA haplotypes. When examining the presumed European component of these two communities, we demonstrate enrichment for Sephardic Jewish ancestry not only for these mutations, but also for other segments as well. Although comparison of both groups to a reference Hispanic/Latino population of Mexicans demonstrated proximity and similarity to other modern day communities derived from a European and Native American two-way admixture, identity-by-descent and Y-chromosome mapping demonstrated signatures of Sephardim in both communities. These findings are consistent with historical accounts of Jewish migration from the realms that comprise modern Spain and Portugal during the Age of Discovery. More importantly, they provide a rationale for the occurrence of mutations typically associated with the Jewish Diaspora in Latin American communities.

Paternal population history of East Asia: sources, patterns, and microevolutionary processes.

Asia has served as a focal point for human migration during much of the Late Pleistocene and Holocene. Clarification of East Asia's role as a source and/or transit point for human dispersals requires that this region's own settlement history be understood. To this end, we examined variation at 52 polymorphic sites on the nonrecombining portion of the Y chromosome (NRY) in 1,383 unrelated males, representing 25 populations from southern East Asia (SEAS), northern East Asia (NEAS), and central Asia (CAS). The polymorphisms defined 45 global haplogroups, 28 of which were present in these three regions. Although heterozygosity levels were similar in all three regions, the average pairwise difference among haplogroups was noticeably smaller in SEAS. Multidimensional scaling analysis indicated a general separation of SEAS versus NEAS and CAS populations, and analysis of molecular variance produced very different values of Phi(ST) in NEAS and SEAS populations. In spatial autocorrelation analyses, the overall correlogram exhibited a clinal pattern; however, the NEAS populations showed evidence of both isolation by distance and ancient clines, whereas there was no evidence of structure in SEAS populations. Nested cladistic analysis demonstrated that population history events and ongoing demographic processes both contributed to the contrasting patterns of NRY variation in NEAS and SEAS. We conclude that the peopling of East Asia was more complex than earlier models had proposed-that is, a multilayered, multidirectional, and multidisciplinary framework is necessary. For instance, in addition to the previously recognized genetic and dental dispersal signals from SEAS to NEAS populations, CAS has made a significant contribution to the contemporary gene pool of NEAS, and the Sino-Tibetan expansion has left traces of a genetic trail from northern to southern China.

Hierarchical patterns of global human Y-chromosome diversity.

We examined 43 biallelic polymorphisms on the nonrecombining portion of the Y chromosome (NRY) in 50 human populations encompassing a total of 2,858 males to study the geographic structure of Y-chromosome variation. Patterns of NRY diversity varied according to geographic region and method/level of comparison. For example, populations from Central Asia had the highest levels of heterozygosity, while African populations exhibited a higher level of mean pairwise differences among haplotypes. At the global level, 36% of the total variance of NRY haplotypes was attributable to differences among populations (i.e., Phi(ST) = 0.36). When a series of AMOVA analyses was performed on different groupings of the 50 populations, high levels of among-groups variance (Phi(CT)) were found between Africans, Native Americans, and a single group containing all 36 remaining populations. The same three population groupings formed distinct clusters in multidimensional scaling plots. A nested cladistic analysis (NCA) demonstrated that both population structure processes (recurrent gene flow restricted by isolation by distance and long-distance dispersals) and population history events (contiguous range expansions and long-distance colonizations) were instrumental in explaining this tripartite division of global NRY diversity. As in our previous analyses of smaller NRY data sets, the NCA detected a global contiguous range expansion out of Africa at the level of the total cladogram. Our new results support a general scenario in which, after an early out-of-Africa range expansion, global-scale patterns of NRY variation were mainly influenced by migrations out of Asia. Two other notable findings of the NCA were (1) Europe as a "receiver" of intercontinental signals primarily from Asia, and (2) the large number of intracontinental signals within Africa. Our AMOVA analyses also supported the hypothesis that patrilocality effects are evident at local and regional scales, rather than at intercontinental and global levels. Finally, our results underscore the importance of subdivision of the human paternal gene pool and imply that caution should be exercised when using models and experimental strategies based on the assumption of panmixia.

Jewish and Middle Eastern non-Jewish populations share a common pool of Y-chromosome biallelic haplotypes.

Haplotypes constructed from Y-chromosome markers were used to trace the paternal origins of the Jewish Diaspora. A set of 18 biallelic polymorphisms was genotyped in 1,371 males from 29 populations, including 7 Jewish (Ashkenazi, Roman, North African, Kurdish, Near Eastern, Yemenite, and Ethiopian) and 16 non-Jewish groups from similar geographic locations. The Jewish populations were characterized by a diverse set of 13 haplotypes that were also present in non-Jewish populations from Africa, Asia, and Europe. A series of analyses was performed to address whether modern Jewish Y-chromosome diversity derives mainly from a common Middle Eastern source population or from admixture with neighboring non-Jewish populations during and after the Diaspora. Despite their long-term residence in different countries and isolation from one another, most Jewish populations were not significantly different from one another at the genetic level. Admixture estimates suggested low levels of European Y-chromosome gene flow into Ashkenazi and Roman Jewish communities. A multidimensional scaling plot placed six of the seven Jewish populations in a relatively tight cluster that was interspersed with Middle Eastern non-Jewish populations, including Palestinians and Syrians. Pairwise differentiation tests further indicated that these Jewish and Middle Eastern non-Jewish populations were not statistically different. The results support the hypothesis that the paternal gene pools of Jewish communities from Europe, North Africa, and the Middle East descended from a common Middle Eastern ancestral population, and suggest that most Jewish communities have remained relatively isolated from neighboring non-Jewish communities during and after the Diaspora.

African and Levantine origins of Pakistani YAP+ Y chromosomes.

We surveyed 9 Pakistani subpopulations for variation on the nonrecombining portion of the Y chromosome. The polymorphic systems examined were the Y-chromosome Alu insertion polymorphism (YAP) at DYS287, 5 single nucleotide polymorphisms, and the tetranucleotide microsatellite DYS19. Y chromosomes carrying the YAP element (YAP+) were found in populations from southwestern Pakistan at frequencies ranging from 2% to 8%, whereas northeastern populations appeared to lack YAP+ chromosomes. In contrast to other South Asian populations, several Pakistani subpopulations had a high frequency of the DYS19*B allele, the most frequent allele in West Asian, North African, and European populations. The combination of alleles at all polymorphic sites gave rise to 9 YAP-DYS19 combination haplotypes in Pakistani populations, including YAP+ haplotypes 4-A, 4-B, 5-C, and 5-E. We hypothesize that the geographic distributions of YAP+ haplotypes 4 and 5 trace separate migratory routes to Pakistan: YAP+ haplotype 5 may have entered Pakistan from the Arabian Peninsula by means of migrations across the Gulf of Oman, whereas males possessing YAP+ haplotype 4 may have traveled over land from the Middle East. These inferences are consistent with ethnohistorical data suggesting that Pakistan's ethnic groups have been influenced by migrations from both African and Levantine source populations.

Ancestral Asian source(s) of new world Y-chromosome founder haplotypes.

Haplotypes constructed from Y-chromosome markers were used to trace the origins of Native Americans. Our sample consisted of 2,198 males from 60 global populations, including 19 Native American and 15 indigenous North Asian groups. A set of 12 biallelic polymorphisms gave rise to 14 unique Y-chromosome haplotypes that were unevenly distributed among the populations. Combining multiallelic variation at two Y-linked microsatellites (DYS19 and DXYS156Y) with the unique haplotypes results in a total of 95 combination haplotypes. Contra previous findings based on Y- chromosome data, our new results suggest the possibility of more than one Native American paternal founder haplotype. We postulate that, of the nine unique haplotypes found in Native Americans, haplotypes 1C and 1F are the best candidates for major New World founder haplotypes, whereas haplotypes 1B, 1I, and 1U may either be founder haplotypes and/or have arrived in the New World via recent admixture. Two of the other four haplotypes (YAP+ haplotypes 4 and 5) are probably present because of post-Columbian admixture, whereas haplotype 1G may have originated in the New World, and the Old World source of the final New World haplotype (1D) remains unresolved. The contrasting distribution patterns of the two major candidate founder haplotypes in Asia and the New World, as well as the results of a nested cladistic analysis, suggest the possibility of more than one paternal migration from the general region of Lake Baikal to the Americas.

Different patterns of variation at the X- and Y-chromosome-linked microsatellite loci DXYS156X and DXYS156Y in human populations.

We compared the global pattern of variation at two homologous microsatellites mapping to the long arm of the X chromosome (DXYS156X) and to the short arm of the Y chromosome (DXYS156Y) in humans. A single pair of oligonucleotide primers amplifies these two nonallelic loci, each of which contains polymorphism in the number of pentanucleotide units. We observed 11 alleles in a sample of 2290 X chromosomes and 2006 Y chromosomes from 50 populations representing 6 major geographic regions. The overlapping size range of the X- and Y-chromosome alleles indicated a more complex distribution of alleles at these two loci than previously reported. Contrasting patterns of X-chromosome-linked and Y-chromosome-linked variation were reflected in statistically significant differences in genetic diversity values among geographic regions and between X and Y chromosomes. Higher levels of diversity characterized the DXYS156X locus in Africa (0.799 +/- 0.004) and the DXYS156Y locus in East Asia (0.700 +/- 0.006) compared with populations from other regions. These different patterns of variation can be explained by a combination of processes at both the molecular and population levels, including variable mutation rates, different effective population sizes, and genetic drift.

Out of Africa and back again: nested cladistic analysis of human Y chromosome variation.

We surveyed nine diallelic polymorphic sites on the Y chromosomes of 1,544 individuals from Africa, Asia, Europe, Oceania, and the New World. Phylogenetic analyses of these nine sites resulted in a tree for 10 distinct Y haplotypes with a coalescence time of approximately 150,000 years. The 10 haplotypes were unevenly distributed among human populations: 5 were restricted to a particular continent, 2 were shared between Africa and Europe, 1 was present only in the Old World, and 2 were found in all geographic regions surveyed. The ancestral haplotype was limited to African populations. Random permutation procedures revealed statistically significant patterns of geographical structuring of this paternal genetic variation. The results of a nested cladistic analysis indicated that these geographical associations arose through a combination of processes, including restricted, recurrent gene flow (isolation by distance) and range expansions. We inferred that one of the oldest events in the nested cladistic analysis was a range expansion out of Africa which resulted in the complete replacement of Y chromosomes throughout the Old World, a finding consistent with many versions of the Out of Africa Replacement Model. A second and more recent range expansion brought Asian Y chromosomes back to Africa without replacing the indigenous African male gene pool. Thus, the previously observed high levels of Y chromosomal genetic diversity in Africa may be due in part to bidirectional population movements. Finally, a comparison of our results with those from nested cladistic analyses of human mtDNA and beta-globin data revealed different patterns of inferences for males and females concerning the relative roles of population history (range expansions) and population structure (recurrent gene flow), thereby adding a new sex-specific component to models of human evolution.

[Genetic analysis of the South Altaian population of the Mendur-Sokkon village, Altai Republic]. / Geneticheskii analiz struktury populiatsii iuzhnykh altaitsev pos. Mendur-Sokkon (Respublika Altai).

This study was a continuation of complex research on the gene pool of indigenous Siberian populations conducted at the Institute of Cytology and Genetics, Siberian Division, Russian Academy of Sciences. In the population of South Altaians from the Mendur-Sokkon village, Ust'-Kanskii raion, Altai Republic, polymorphism for the following genetic markers was studied: blood groups ABO, MNSs, Rhesus, Kell, Duffy, and P; erythrocyte acid phosphatase (AcP); phosphoglucomutase 1 (PGM1); haptoglobin (Hp); and transferrin (Tf). The genetic position of South Altaians relative to the populations of the European part of Russia, Siberia, and the Urals was estimated. It was demonstrated that the gene pool of the South Altaian population of Mendur-Sokkon possessed both Caucasoid and Mongoloid genetic characteristics, with the latter prevailing. Genetically, this population is most closely related to Mongols and Nentsis. The genetic distance between South and North Altaians was large; this agreed with earlier genetic data and confirmed anthropological and ethnographic evidence indicating that these two groups had different backgrounds and were at different stages of ethnogenesis.

Y chromosome markers and Trans-Bering Strait dispersals.

Five polymorphisms involving two paternally inherited loci were surveyed in 38 world populations (n = 1,631) to investigate the origins of Native Americans. One of the six Y chromosome combination haplotypes (1T) was found at relatively high frequencies (17.8-75.0%) in nine Native American populations (n = 206) representing the three major linguistic divisions in the New World. Overall, these data do not support the Greenberg et al. (1986) tripartite model for the early peopling of the Americas. The 1T haplotype was also discovered at a low frequency in Siberian Eskimos (3/22), Chukchi (1/6), and Evens (1/65) but was absent from 17 other Asian populations (n = 987). The perplexing presence of the 1T haplotype in northeastern Siberia may be due to back-migration from the New World to Asia.

The geographic distribution of human Y chromosome variation.

We examined variation on the nonrecombining portion of the human Y chromosome to investigate human evolution during the last 200,000 years. The Y-specific polymorphic sites included the Y Alu insertional polymorphism or "YAP" element (DYS287), the poly(A) tail associated with the YAP element, three point mutations in close association with the YAP insertion site, an A-G polymorphic transition (DYS271), and a tetranucleotide microsatellite (DYS19). Global variation at the five bi-allelic sites (DYS271, DYS287, and the three point mutations) gave rise to five "YAP haplotypes" in 60 populations from Africa, Europe, Asia, Australasia, and the New World (n = 1500). Combining the multi-allelic variation at the microsatellite loci (poly(A) tail and DYS19) with the YAP haplotypes resulted in a total of 27 "combination haplotypes". All five of the YAP haplotypes and 21 of the 27 combination haplotypes were found in African populations, which had greater haplotype diversity than did populations from other geographical locations. Only subsets of the five YAP haplotypes were found outside of Africa. Patterns of observed variation were compatible with a variety of hypotheses, including multiple human migrations and range expansions.

[The gene pool of native inhabitants of the Samburg tundra]. / Genofond korennykh zhitelei Samburgskoi tundry.

This study continues a series of investigations of the gene pool of native Siberian ethnic groups. In a population of Tundra Nentsi (Northern Samoyeds) and a group of Komi-Zyryans (Finno-Ugrian) (Samburg settlement, Tyumenskaya oblast, Yamalo-Nenetskii Autonomous okrug), gene markers of the following genetic systems were studied: blood groups (ABO, MNSs, Rhesus, Kell, Duffy, and P), erythrocyte acid phosphatase (AcP), phosphoglucomutase 1 (PGM 1), haptoglobin (Hp), and transferrin (Tf). The population of Samburg Tundra Nentsi was shown to have a close genetic relationship with the "core" of the Forest Nentsi population. In Northern Samoyeds, three carriers of the rare allele K (blood group Kell) were found for the first time. It is suggested that this allele was transferred into the population of Tundra Nentsi from Komi. Samburg Tundra Nentsi are found to have the maximum frequency of the allele PGM 1 (Posphoglucomutase 1) among aboriginal populations of northern Asia. Analysis of original data and the literature revealed a significant genetic distance between the Komi and Northern Samoyed populations. It was shown that Samburg Komi occupy an intermediate position between the clusters of Nenets populations and Finno-Ugrians (Komi) living in Komi Republic.

[Restriction-deletion polymorphism of mitochondrial DNA region V in some populations of aboriginal residents of Siberia and the Far East]. / Restriktsionno-deletsionnyi polimorfizm V raiona mitokhondrial'noi DNK v nekotorykh populiatsiiakh korennykh zhitelei Sibiri i dal'nego vostoka.

The distribution of a deletion and of an Ava II site in region V of mitochondrial DNA (mtDNA) was studied in five populations of native inhabitants of the Asian part of Russia, including Chukchi, Asian Eskimos, Evenks, Buryats, and Northern Sel'kups. A deletion with a frequency of 6.3% was found only in Buryats, In Chukchi and Eskimos the AvaII site was not found. A maximal frequency of 11.3% was observed in the Evenks. A comparison with published data was conducted; it revealed a gradient of decreasing frequency of the deletion from Southeast Asia to the North, with its complete absence in the circumpolar regions. In the territory of northeast Asia, all three mitotypes are found, formed by a combination of two polymorphic markers of mtDNA region V, which were found earlier in humans in the New World. The data obtained necessitates a more detailed analysis of the population polymorphism of mtDNA in this region of Asia.

[Heterozygosity and fertility in the Northern Selkup tribe]. / Geterozigotnost' i plodovitost' u severnykh sel'kupov.

The relationship between heterozygosity for 11 polymorphic loci and fertility of women having passed the menopause was studied in North-Siberian tribe North Selkup. Women with low level of heterozygosity were characterized by the highest values of variance of the number of livebirths and the index of early reproductive loss.

[Genetic and ecological study of aboriginal inhabitants of the Siberian northeast. IV. Genotype and genetic structure of three modern populations of Yakutia]. / Geneticheskoe i ékologichekoe izuchenie korennykh zhitelei severo- vostoka Siberi. IV. Genotip i geneticheskaia struktura trekh sovremennykh populiatsii zvenov iakutii.

Three separate and reproductively isolated populations living at present in boreal forest and tundra area in Eastern Siberia were studied. Blood groups (AB0, MNSs, Rhesus, Duffy, P. Diego), immunoglobulin allotypes--G1m (z, a, x, f), G3m (b, b0, b1, b3, s, t), Hp, Tf, PGM1, AcP, 6-PGD were tested in blood samples obtained from total 570 individuals. Analysis of covariance and variance matrices containing gene frequencies of the Nganasans, Reindeer Chukchi, the Yugaghir and the Evens has revealed major aspects of regional genetic structure which is in good accordance with regional history and geography.

[Relation between heterozygosity and fertility in Forest Nentzy and Nganasan tribes]. / Izuchenie sviazi geterozigotnosti s parametrami plodovitosti u lesnykh nentsev i nganasan.

The relationship between heterozygosity for 13 polymorphic loci and fertility of women having passed the menopause was studied in two North-Siberian tribes: Forest Nentzy (N = 108) and Nganasans (N = 68). The number of pregnancies positively correlated with the individual heterozygosity (r = 0.2910 +/- 0.1063; P less than 0.01) in Forest Nentzy, while in Nganasans this correlation was absent. Women with the average level of individual heterozygosity were characterized by minimal values of variation in pregnancies' number and maximal Q index of realized fertility. It is concluded that the average level of individual heterozygosity is optimal for both tribes.

[Genetic and ecological study of aboriginal populations of northeastern Siberia. II. Polymorphic blood systems, immunoglobulin allotypes and other genetic markers in asian eskimos. Genetic structure of Bering sea eskimos]. / Geneticheskoe i ékologicheskoe izuchenie korennykh zhitelei severo-vostoka Sibiri. Soobshchenie II. Polimorfnye sistemy krovi, allotipy immunoglobulinov i drugie geneticheskie markery u aziatskikh éskimosov. Geneticheskaia struktura éskimosov Beringova moria.

Blood groups, immunoglobulin allotypes, serum proteins and red cell enzymes were tested in four populations of Asiatic Eskimos. 12 of 16 gene loci studied were found to be polymorphic. Analysis of covariance and variance matrices for gene frequencies of 8 Bering Sea populations revealed major aspects of regional genetic structure. Regression of average heterozygosity on genetic distance from centroid permitted us to interpret it in the light of counterbalancing action of systematic and non-systematic pressure. Analysis of R matrix containing gene frequencies for both Eskimo and Chukchi populations revealed two different clusters - more heterogeneous Eskimo cluster and less heterogeneous Chukchi cluster. Good fit was observed between regional genetic structure, history and geography.

[Genetic and ecological study of aboriginal populations of northeastern Siberia. I. Gm-haplotypes and their frequency in 10 chukchi populations. Genetic structure of reindeer chukchi]. / Geneticheskoe i ékologicheskoe izuchenie korennykh zhitelei severo-vostoka Sibiri. Soobshchenie I. Gm-gaplotipy i ikh chastota v desiati chukotskikh populiatsiiakh. Geneticheskaia struktura olennykh chukchei.

G1m (z, a, x, f) and G3m (g, b0, b1, b3, b5, s, t) allotypes were tested in 1079 Chukchi inhabitants of interior Chukotka and adjacent Kamchatka. Genetic variation at this particular locus is provided by the presence of three haplotypes, namely, za;g, zax;g and za;bO35st, revealed with mean frequencies of 0.748, 0.089 and 0.154, respectively. Traces of Caucasian Gm (f;bO135) haplotype were observed in 9 of 10 populations studied. Judging from its frequency in the whole group (0.009), European admixture in Reindeer Chukchi did not exceed 1.3%. Analysis of covariance and variance matrices containing gene frequencies for 11 polymorphic loci revealed the aspects of genetic structure. Simultaneously, the action of systematic versus nonsystematic pressure was also evaluated and interpreted in the light of historical and ecological events.

[Population structure of the forest Nentsi. V. F-statistics, genetic distances and the average heterozygosity (compared to the Nganasani)]. / Populiatsionnaia struktura lesnykh nentsev. Soobshchenie V. F-statistika, geneticheskie distantsii i sredniaia geterozigotnost' (v sopostavlenii s nganasanami).

Aspects of population structure within two of the least disintegrated "anthropological isolates" in north-western (forest Nentsi) and north-central (Nganasani) Siberia were analysed on the basis of 14 polymorphic loci. The mean FIS values were found to be 0.008 in the forest Nentsi and -0.038 in the Nganasani. The negative FIS in the latter may be due to avoidance of close inbreeding. This is not the case with the Forest Nentsi who prefer matings of the uncle-niece and first cousin's type. The mean RST(FST) values of 0.026 for the forest Nentsi and 0.009 for less heterogeneous Nganasani fall within the range of values found in subdivided human groups with a similar pattern of material culture and economy. Analysis of covariance and variance matrices containing gene frequencies for seven forest Nentsi and three Nganasani subdivisions indicate that the population structure of both groups is the product of the counterbalancing action of genetic drift and migration. Pairwise genetic and geographic distance matrices between subpopulations within both groups are highly correlated, allowing us to ascribe more than 90 percent of variation among subdivisions of the Nganasani and almost 70 percent in the forest Nentsi to the effects of geographic barriers, namely distance. Mean locus heterozygosity was found to be higher in the forest Nentsi (0.332) than in the Nganasani (0.286) reflecting pronounced difference in their histories.