Ancient genomic time transect from the Central Asian Steppe unravels the history of the Scythians

The Scythians were a multitude of horse-warrior nomad cultures dwelling in the Eurasian steppe during the first millennium BCE. Because of the lack of first-hand written records, little is known about the origins and relations among the different cultures. To address these questions, we produced genome-wide data for 111 ancient individuals retrieved from 39 archaeological sites from the first millennia BCE and CE across the Central Asian Steppe. We uncovered major admixture events in the Late Bronze Age forming the genetic substratum for two main Iron Age gene-pools emerging around the Altai and the Urals respectively. Their demise was mirrored by new genetic turnovers, linked to the spread of the eastern nomad empires in the first centuries CE. Compared to the high genetic heterogeneity of the past, the homogenization of the present-day Kazakhs gene pool is notable, likely a result of 400 years of strict exogamous social rules.Introduction Results - The IA transition in the Kazakh Steppe - Admixture modeling of IA steppe populations - Post-IA genetic turnovers in the Kazakh Steppe - Dating ancient admixture - Present-day Kazakhs Discussion Material and methods - Radiocarbon dating - DNA extraction, library preparations, and sequencing - Modern DNA genotyping and quality controls - Ancient DNA data processing -- Raw data -- Authentication and contamination estimate -- Genotyping -- Sex determination -- Genetic relatedness estimation - Uniparental haplogroup assignment - Population structure analyses - Individual labeling and population grouping criteria - F-statistics and ancestry modeling - Admixture dating - CHROMOPAINTER and fineSTRUCTURE analyse

The genetic history of admixture across inner Eurasia

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this record.Data Availability. Genome-wide sequence data of two Botai individuals (BAM format) are available at the European Nucleotide Archive under the accession number PRJEB31152 (ERP113669). Eigenstrat format array genotype data of 763 present-day individuals and 1240K pulldown genotype data of two ancient Botai individuals are available at the Edmond data repository of the Max Planck Society (https://edmond.mpdl.mpg.de/imeji/collection/Aoh9c69DscnxSNjm?q=).The indigenous populations of inner Eurasia, a huge geographic region covering the central Eurasian steppe and the northern Eurasian taiga and tundra, harbor tremendous diversity in their genes, cultures and languages. In this study, we report novel genome-wide data for 763 individuals from Armenia, Georgia, Kazakhstan, Moldova, Mongolia, Russia, Tajikistan, Ukraine, and Uzbekistan. We furthermore report additional damage-reduced genome-wide data of two previously published individuals from the Eneolithic Botai culture in Kazakhstan (~5,400 BP). We find that present-day inner Eurasian populations are structured into three distinct admixture clines stretching between various western and eastern Eurasian ancestries, mirroring geography. The Botai and more recent ancient genomes from Siberia show a decrease in contribution from so-called “ancient North Eurasian” ancestry over time, detectable only in the northern-most “forest-tundra” cline. The intermediate “steppe-forest” cline descends from the Late Bronze Age steppe ancestries, while the “southern steppe” cline further to the South shows a strong West/South Asian influence. Ancient genomes suggest a northward spread of the southern steppe cline in Central Asia during the first millennium BC. Finally, the genetic structure of Caucasus populations highlights a role of the Caucasus Mountains as a barrier to gene flow and suggests a post-Neolithic gene flow into North Caucasus populations from the steppe.Max Planck SocietyEuropean Research Council (ERC)Russian Foundation for Basic Research (RFBR)Russian Scientific FundNational Science FoundationU.S. National Institutes of HealthAllen Discovery CenterUniversity of OstravaCzech Ministry of EducationXiamen UniversityFundamental Research Funds for the Central UniversitiesMES R

Stone Age Yersinia pestis genomes shed light on the early evolution, diversity, and ecology of plague

The bacterial pathogenYersinia pestisgave rise to devastating outbreaks throughouthuman history, and ancient DNA evidence has shown it afflicted human populations asfar back as the Neolithic.Y. pestisgenomes recovered from the Eurasian Late Neolithic/Early Bronze Age (LNBA) period have uncovered key evolutionary steps that led to itsemergence from aYersinia pseudotuberculosis-like progenitor; however, the number ofreconstructed LNBA genomes are too few to explore its diversity during this criticalperiod of development. Here, we present 17Y. pestisgenomes dating to 5,000 to 2,500y BP from a wide geographic expanse across Eurasia. This increased dataset enabled usto explore correlations between temporal, geographical, and genetic distance. Ourresults suggest a nonflea-adapted and potentially extinct single lineage that persistedover millennia without significant parallel diversification, accompanied by rapid dis-persal across continents throughout this period, a trend not observed in other pathogensfor which ancient genomes are available. A stepwise pattern of gene loss provides fur-ther clues on its early evolution and potential adaptation. We also discover the presenceof theflea-adapted form ofY. pestisin Bronze Age Iberia, previously only identified inin the Caucasus and the Volga regions, suggesting a much wider geographic spread ofthis form ofY. pestis. Together, these data reveal the dynamic nature of plague’s forma-tive years in terms of its early evolution and ecology

Ten millennia of hepatitis B virus evolution

Hepatitis B virus (HBV) has been infecting humans for millennia and remains a global health problem, but its past diversity and dispersal routes are largely unknown. We generated HBV genomic data from 137 Eurasians and Native Americans dated between similar to 10,500 and similar to 400 years ago. We date the most recent common ancestor of all HBV lineages to between similar to 20,000 and 12,000 years ago, with the virus present in European and South American hunter-gatherers during the early Holocene. After the European Neolithic transition, Mesolithic HBV strains were replaced by a lineage likely disseminated by early farmers that prevailed throughout western Eurasia for similar to 4000 years, declining around the end of the 2nd millennium BCE. The only remnant of this prehistoric HBV diversity is the rare genotype G, which appears to have reemerged during the HIV pandemic.Molecular Technology and Informatics for Personalised Medicine and Healt

Ten millennia of hepatitis B virus evolution

Hepatitis B virus (HBV) has been infecting humans for millennia and remains a global health problem, but its past diversity and dispersal routes are largely unknown. We generated HBV genomic data from 137 Eurasians and Native Americans dated between ~10,500 and ~400 years ago. We date the most recent common ancestor of all HBV lineages to between ~20,000 and 12,000 years ago, with the virus present in European and South American hunter-gatherers during the early Holocene. After the European Neolithic transition, Mesolithic HBV strains were replaced by a lineage likely disseminated by early farmers that prevailed throughout western Eurasia for ~4000 years, declining around the end of the 2nd millennium BCE. The only remnant of this prehistoric HBV diversity is the rare genotype G, which appears to have reemerged during the HIV pandemic

Analysis of K-ras codon 12 and TP53 mutations in patients with advanced colorectal carcinoma

Background. Colorectal cancer (CRC) is one of the most common types of cancer, affecting 3 - 5% of the global population. K-ras protooncogene and TP53 tumour suppressor gene mutations are among the most common genetic alterations detected in advanced colorectaltumours.Objective. To investigate the role of K-ras codon 12 and TP53 exons 5 - 9 mutations in late-stage CRC patients.Methods. Blood samples were collected from 249 CRC patients, of whom 147 presented with advanced carcinoma. K-ras codon 12 mutations were analysed using polymerase chain reaction-restriction fragment length polymorphism, while direct sequencing was used in screening for TP53 exons 5 - 9 mutations.Results. No significant changes were observed in TP53 exons 5 - 9, except for two cases in which nucleotide replacements were observed in the non-coding regions in intron 4 (c.376-19C>T) and intron 9 (c.993+12T>C). Heterozygous mutations in K-ras codon 12 were observed in 79 individuals suffering from advanced CRC (53.7%). Colon and rectal tumours were equally distributed among the heterozygotes, but colon tumours were mostly present in wild-type homozygotes (84.6%). There was also a predominance of Caucasians among heterozygotes and a predominance of Asians among the wild-type homozygotes.Conclusion. Analysis of peripheral blood samples of CRC patients suffering from advanced carcinoma has prognostic value only for K-ras codon 12 mutations, and not for TP53 mutations

Characterizing the genetic history of admixture across inner Eurasia

The indigenous populations of inner Eurasia, a huge geographic region covering the central Eurasian steppe and the northern Eurasian taiga and tundra, harbor tremendous diversity in their genes, cultures and languages. In this study, we report novel genome-wide data for 763 individuals from Armenia, Georgia, Kazakhstan, Moldova, Mongolia, Russia, Tajikistan, Ukraine, and Uzbekistan. We furthermore report genome-wide data of two Eneolithic individuals (~5,400 years before present) associated with the Botai culture in northern Kazakhstan. We find that inner Eurasian populations are structured into three distinct admixture clines stretching between various western and eastern Eurasian ancestries. This genetic separation is well mirrored by geography. The ancient Botai genomes suggest yet another layer of admixture in inner Eurasia that involves Mesolithic hunter-gatherers in Europe, the Upper Paleolithic southern Siberians and East Asians. Admixture modeling of ancient and modern populations suggests an overwriting of this ancient structure in the Altai-Sayan region by migrations of western steppe herders, but partial retaining of this ancient North Eurasian-related cline further to the North. Finally, the genetic structure of Caucasus populations highlights a role of the Caucasus Mountains as a barrier to gene flow and suggests a post-Neolithic gene flow into North Caucasus populations from the steppe