Localizing Ashkenazic Jews to Primeval Villages in the Ancient Iranian Lands of Ashkenaz

TheYiddishlanguageisover1,000yearsoldandincorporatesGerman,Slavic,andHebrewelements.TheprevalentviewclaimsYiddish hasaGermanorigin,whereastheopposingviewpositsaSlavicoriginwithstrongIranianandweakTurkicsubstrata.Oneofthemajor difficulties in deciding between these hypotheses is the unknown geographical origin of Yiddish speaking Ashkenazic Jews (AJs). An analysis of 393 Ashkenazic, Iranian, and mountain Jews and over 600 non-Jewish genomes demonstrated that Greeks, Romans, Iranians,andTurksexhibitthehighestgeneticsimilaritywithAJs.TheGeographicPopulationStructureanalysislocalizedmostAJsalong major primeval trade routes in northeastern Turkey adjacent to primeval villages with names that may be derived from “Ashkenaz.” IranianandmountainJewswerelocalizedalongtraderoutesontheTurkey’seasternborder.Lossofmaternalhaplogroupswasevident in non-Yiddish speaking AJs. Our results suggest that AJs originated from a Slavo-Iranian confederation, which the Jews call “Ashkenazic” (i.e., “Scythian”), though these Jews probably spoke Persian and/or Ossete. This is compatible with linguistic evidence suggesting that Yiddish is a Slavic language created by Irano-Turko-Slavic Jewish merchants along the Silk Roads as a cryptic trade language, spoken only by its originators to gain an advantage in trade. Later, in the 9th century, Yiddish underwent relexification by adoptinganewvocabularythatconsistsofaminorityofGermanandHebrewandamajorityofnewlycoinedGermanoidandHebroid elements that replaced most of the original Eastern Slavic and Sorbian vocabularies, while keeping the original grammars intact

The genetic structure of south Asian populations as revealed by 650 000 SNPs

The analyses of dense marker sets covering the whole genome has revolutionised the field of (human) population genetics. Driven largely by the needs of biomedical research, these new data are helping to unveil our demographic past, exemplified by the study of mtDNA and Y-chromosome variation during the past ∼20 years. We have analysed (Illumina 650K SNPs) over 320 new samples from South and Central Asia and the Caucasus, together with the publicly available databases (HGDP panel and our published data set of ∼600 Eurasian samples) and illustrated the power of full genome analyses by addressing two specific questions. (i) What is the nature of genetic continuity and discontinuity between South Asia, Middle East and Central Asia? (ii) What are the genetic origins of the Munda speakers of India? We use principal component and structure-like analyses to reveal the structure in the genome wide SNP data. The most striking feature of the genetic structure of South Asian populations is the clear separation of the Indus valley and southern India populations. The genetic component prevalent in the latter region is marginal in the former and absent outside South Asia. By contrast, the component ubiquitous to Indus valley is also present (∼30-40 %) among Indo-European speakers from Ganges valley and Dravidic speakers in southern India. Furthermore, this component can also be found in Central Asia and the Caucasus as well as in Middle East. We explored possibilities to identify the source region for this genetic component. Alternative models put the origins of Munda languages speakers either in South Asia (the Munda speakers sport exclusively autochthonous South Asian mtDNA variants) or in Southeast Asia, where the other Austro Asiatic languages have spread. Y-chromosome variation supports the latter model through sharing of hg O2a in both regions. We show that in addition to the dominant ancestry component being shared between the Indian Dravidic and Munda speakers, up to 30% of Munda speakers retain an ancestry component otherwise prevalent in East Asia. There is no widespread sign of South Asian ancestry component in Southeast Asia. This provides genomic support to the model by which Indian Austro-Asiatic populations derive from dispersal from Southeast/East Asia, followed by an extensive admixture with local Indian populations

Y-chromosomal connection between Hungarians and geographically distant populations of the Ural Mountain region and West Siberia

Hungarians who live in Central Europe today are one of the westernmost Uralic speakers. Despite of the proposed Volga-Ural/West Siberian roots of the Hungarian language, the present-day Hungarian gene pool is highly similar to that of the surrounding Indo-European speaking populations. However, a limited portion of specific Y-chromosomal lineages from haplogroup N, sometimes associated with the spread of Uralic languages, link modern Hungarians with populations living close to the Ural Mountain range on the border of Europe and Asia. Here we investigate the paternal genetic connection between these spatially separated populations. We reconstruct the phylogeny of N3a4-Z1936 clade by using 33 high-coverage Y-chromosomal sequences and estimate the coalescent times of its sub-clades. We genotype close to 5000 samples from 46 Eurasian populations to show the presence of N3a4-B539 lineages among Hungarians and in the populations from Ural Mountain region, including Ob-Ugric-speakers from West Siberia who are geographically distant but linguistically closest to Hungarians. This sub-clade splits from its sister-branch N3a4-B535, frequent today among Northeast European Uralic speakers, 4000–5000 ya, which is in the time-frame of the proposed divergence of Ugric languages

Uniparental Genetic Heritage of Belarusians: Encounter of Rare Middle Eastern Matrilineages with a Central European Mitochondrial DNA Pool

Ethnic Belarusians make up more than 80% of the nine and half million people inhabiting the Republic of Belarus. Belarusians together with Ukrainians and Russians represent the East Slavic linguistic group, largest both in numbers and territory, inhabiting East Europe alongside Baltic-, Finno-Permic- and Turkic-speaking people. Till date, only a limited number of low resolution genetic studies have been performed on this population. Therefore, with the phylogeographic analysis of 565 Y-chromosomes and 267 mitochondrial DNAs from six well covered geographic sub-regions of Belarus we strove to complement the existing genetic profile of eastern Europeans. Our results reveal that around 80% of the paternal Belarusian gene pool is composed of R1a, I2a and N1c Y-chromosome haplogroups – a profile which is very similar to the two other eastern European populations – Ukrainians and Russians. The maternal Belarusian gene pool encompasses a full range of West Eurasian haplogroups and agrees well with the genetic structure of central-east European populations. Our data attest that latitudinal gradients characterize the variation of the uniparentally transmitted gene pools of modern Belarusians. In particular, the Y-chromosome reflects movements of people in central-east Europe, starting probably as early as the beginning of the Holocene. Furthermore, the matrilineal legacy of Belarusians retains two rare mitochondrial DNA haplogroups, N1a3 and N3, whose phylogeographies were explored in detail after de novo sequencing of 20 and 13 complete mitogenomes, respectively, from all over Eurasia. Our phylogeographic analyses reveal that two mitochondrial DNA lineages, N3 and N1a3, both of Middle Eastern origin, might mark distinct events of matrilineal gene flow to Europe: during the mid-Holocene period and around the Pleistocene-Holocene transition, respectively

Excess fermentation and lactic acidosis as detrimental functions of the gut microbes in treatment-naive TB patients

IntroductionThe link between gut microbiota and host immunity motivated numerous studies of the gut microbiome in tuberculosis (TB) patients. However, these studies did not explore the metabolic capacity of the gut community, which is a key axis of impact on the host’s immunity.MethodsWe used deep sequencing of fecal samples from 23 treatment-naive TB patients and 48 healthy donors to reconstruct the gut microbiome’s metabolic capacity and strain/species-level content.ResultsWe show that the systematic depletion of the commensal flora of the large intestine, Bacteroidetes, and an increase in Actinobacteria, Firmicutes, and Proteobacteria such as Streptococcaceae, Erysipelotrichaceae, Lachnospiraceae, and Enterobacteriaceae explains the strong taxonomic divergence of the gut community in TB patients. The cumulative expansion of diverse disease-associated pathobionts in patients reached 1/4 of the total gut microbiota, suggesting a heavy toll on host immunity along with MTB infection. Reconstruction of metabolic pathways showed that the microbial community in patients shifted toward rapid growth using glycolysis and excess fermentation to produce acetate and lactate. Higher glucose availability in the intestine likely drives fermentation to lactate and growth, causing acidosis and endotoxemia.DiscussionExcessive fermentation and lactic acidosis likely characterize TB patients’ disturbed gut microbiomes. Since lactic acidosis strongly suppresses the normal gut flora, directly interferes with macrophage function, and is linked to mortality in TB patients, our findings highlight gut lactate acidosis as a novel research focus. If confirmed, gut acidosis may be a novel potential host-directed treatment target to augment traditional TB treatment

Современные представления о роли кишечной микробиоты в развитии туберкулеза легких

The review presents data from 55 publications describing the relationship between the gut microbiome and tuberculosis. It presents possible mechanisms by which the intestinal microbiota can influence various parts of the immune system.It describes the effect of anti-tuberculosis drugs on the intestinal microbiome as well as possible prospects for the use of probiotics in the treatment and prevention of tuberculosis.В обзоре представлены данные из 55 литературных источников, описывающих взаимосвязь микробиома кишечника c туберкулезом. Обсуждаются механизмы, с помощью которых микробиота кишечника может влиять на различные звенья иммунной системы, представлены данные о влиянии противотуберкулезных препаратов на микробиом кишечника, а также возможные перспективы использования пробиотиков в лечении и профилактике туберкулеза

Reconstructing Druze population history

The Druze are an aggregate of communities in the Levant and Near East living almost exclusively in the mountains of Syria, Lebanon and Israel whose ~1000 year old religion formally opposes mixed marriages and conversions. Despite increasing interest in genetics of the population structure of the Druze, their population history remains unknown. We investigated the genetic relationships between Israeli Druze and both modern and ancient populations. We evaluated our findings in light of three hypotheses purporting to explain Druze history that posit Arabian, Persian or mixed Near Eastern-Levantine roots. The biogeographical analysis localised proto-Druze to the mountainous regions of southeastern Turkey, northern Iraq and southeast Syria and their descendants clustered along a trajectory between these two regions. The mixed Near Eastern-Middle Eastern localisation of the Druze, shown using both modern and ancient DNA data, is distinct from that of neighbouring Syrians, Palestinians and most of the Lebanese, who exhibit a high affinity to the Levant. Druze biogeographic affinity, migration patterns, time of emergence and genetic similarity to Near Eastern populations are highly suggestive of Armenian-Turkish ancestries for the proto-Druze

The GenoChip: A New Tool for Genetic Anthropology

The Genographic Project is an international effort aimed at charting human migratory history. The project is nonprofit and nonmedical, and, through its Legacy Fund, supports locally led efforts to preserve indigenous and traditional cultures. Although the first phase of the project was focused on uniparentally inherited markers on the Y-chromosome and mitochondrial DNA (mtDNA), the current phase focuses on markers from across the entire genome to obtain a more complete understanding of human genetic variation. Although many commercial arrays exist for genome-wide single-nucleotide polymorphism (SNP) genotyping, they were designed for medical genetic studies and contain medically related markers that are inappropriate for global population genetic studies. GenoChip, the Genographic Project’s new genotyping array, was designed to resolve these issues and enable higher resolution research into outstanding questions in genetic anthropology. The GenoChip includes ancestry informative markers obtained for over 450 human populations, an ancient human (Saqqaq), and two archaic hominins (Neanderthal and Denisovan) and was designed to identify all known Y-chromosome and mtDNA haplogroups. The chip was carefully vetted to avoid inclusion of medically relevant markers. To demonstrate its capabilities, we compared the FST distributions of GenoChip SNPs to those of two commercial arrays. Although all arrays yielded similarly shaped (inverse J) FST distributions, the GenoChip autosomal and X-chromosomal distributions had the highest mean FST, attesting to its ability to discern subpopulations. The chip performances are illustrated in a principal component analysis for 14 worldwide populations. In summary, the GenoChip is a dedicated genotyping platform for genetic anthropology. With an unprecedented number of approximately 12,000 Y-chromosomal and approximately 3,300 mtDNA SNPs and over 130,000 autosomal and X-chromosomal SNPs without any known health, medical, or phenotypic relevance, the GenoChip is a useful tool for genetic anthropology and population genetics

East Eurasian ancestry in the middle of Europe: Genetic footprints of Steppe nomads in the genomes of Belarusian Lipka Tatars

Medieval era encounters of nomadic groups of the Eurasian Steppe and largely sedentary East Europeans had a variety of demographic and cultural consequences. Amongst these outcomes was the emergence of the Lipka Tatars-a Slavic-speaking Sunni-Muslim minority residing in modern Belarus, Lithuania and Poland, whose ancestors arrived in these territories via several migration waves, mainly from the Golden Horde. Our results show that Belarusian Lipka Tatars share a substantial part of their gene pool with Europeans as indicated by their Y-chromosomal, mitochondrial and autosomal DNA variation. Nevertheless, Belarusian Lipkas still retain a strong genetic signal of their nomadic ancestry, witnessed by the presence of common Y-chromosomal and mitochondrial DNA variants as well as autosomal segments identical by descent between Lipkas and East Eurasians from temperate and northern regions. Hence, we document Lipka Tatars as a unique example of former Medieval migrants into Central Europe, who became sedentary, changed language to Slavic, yet preserved their faith and retained, both uni-and bi-parentally, a clear genetic echo of a complex population interplay throughout the Eurasian Steppe Belt, extending from Central Europe to northern China

Genes reveal traces of common recent demographic history for most of the Uralic-speaking populations

Background: The genetic origins of Uralic speakers from across a vast territory in the temperate zone of North Eurasia have remained elusive. Previous studies have shown contrasting proportions of Eastern and Western Eurasian ancestry in their mitochondrial and Y chromosomal gene pools. While the maternal lineages reflect by and large the geographic background of a given Uralic-speaking population, the frequency of Y chromosomes of Eastern Eurasian origin is distinctively high among European Uralic speakers. The autosomal variation of Uralic speakers, however, has not yet been studied comprehensively.Results: Here, we present a genome-wide analysis of 15 Uralic-speaking populations which cover all main groups of the linguistic family. We show that contemporary Uralic speakers are genetically very similar to their local geographical neighbours. However, when studying relationships among geographically distant populations, we find that most of the Uralic speakers and some of their neighbours share a genetic component of possibly Siberian origin. Additionally, we show that most Uralic speakers share significantly more genomic segments identity-by-descent with each other than with geographically equidistant speakers of other languages. We find that correlated genome-wide genetic and lexical distances among Uralic speakers suggest co-dispersion of genes and languages. Yet, we do not find long-range genetic ties between Estonians and Hungarians with their linguistic sisters that would distinguish them from their non-Uralic-speaking neighbours.Conclusions: We show that most Uralic speakers share a distinct ancestry component of likely Siberian origin, which suggests that the spread of Uralic languages involved at least some demic component