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

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three genomic nomenclature systems to all sequence data from the World Health Organization European Region available until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation, compare the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2

Genomic analyses inform on migration events during the peopling of Eurasia.

High-coverage whole-genome sequence studies have so far focused on a limited number of geographically restricted populations, or been targeted at specific diseases, such as cancer. Nevertheless, the availability of high-resolution genomic data has led to the development of new methodologies for inferring population history and refuelled the debate on the mutation rate in humans. Here we present the Estonian Biocentre Human Genome Diversity Panel (EGDP), a dataset of 483 high-coverage human genomes from 148 populations worldwide, including 379 new genomes from 125 populations, which we group into diversity and selection sets. We analyse this dataset to refine estimates of continent-wide patterns of heterozygosity, long- and short-distance gene flow, archaic admixture, and changes in effective population size through time as well as for signals of positive or balancing selection. We find a genetic signature in present-day Papuans that suggests that at least 2% of their genome originates from an early and largely extinct expansion of anatomically modern humans (AMHs) out of Africa. Together with evidence from the western Asian fossil record, and admixture between AMHs and Neanderthals predating the main Eurasian expansion, our results contribute to the mounting evidence for the presence of AMHs out of Africa earlier than 75,000 years ago.Support was provided by: Estonian Research Infrastructure Roadmap grant no 3.2.0304.11-0312; Australian Research Council Discovery grants (DP110102635 and DP140101405) (D.M.L., M.W. and E.W.); Danish National Research Foundation; the Lundbeck Foundation and KU2016 (E.W.); ERC Starting Investigator grant (FP7 - 261213) (T.K.); Estonian Research Council grant PUT766 (G.C. and M.K.); EU European Regional Development Fund through the Centre of Excellence in Genomics to Estonian Biocentre (R.V.; M.Me. and A.Me.), and Centre of Excellence for Genomics and Translational Medicine Project No. 2014-2020.4.01.15-0012 to EGC of UT (A.Me.) and EBC (M.Me.); Estonian Institutional Research grant IUT24-1 (L.S., M.J., A.K., B.Y., K.T., C.B.M., Le.S., H.Sa., S.L., D.M.B., E.M., R.V., G.H., M.K., G.C., T.K. and M.Me.) and IUT20-60 (A.Me.); French Ministry of Foreign and European Affairs and French ANR grant number ANR-14-CE31-0013-01 (F.-X.R.); Gates Cambridge Trust Funding (E.J.); ICG SB RAS (No. VI.58.1.1) (D.V.L.); Leverhulme Programme grant no. RP2011-R-045 (A.B.M., P.G. and M.G.T.); Ministry of Education and Science of Russia; Project 6.656.2014/K (S.A.F.); NEFREX grant funded by the European Union (People Marie Curie Actions; International Research Staff Exchange Scheme; call FP7-PEOPLE-2012-IRSES-number 318979) (M.Me., G.H. and M.K.); NIH grants 5DP1ES022577 05, 1R01DK104339-01, and 1R01GM113657-01 (S.Tis.); Russian Foundation for Basic Research (grant N 14-06-00180a) (M.G.); Russian Foundation for Basic Research; grant 16-04-00890 (O.B. and E.B); Russian Science Foundation grant 14-14-00827 (O.B.); The Russian Foundation for Basic Research (14-04-00725-a), The Russian Humanitarian Scientific Foundation (13-11-02014) and the Program of the Basic Research of the RAS Presidium “Biological diversity” (E.K.K.); Wellcome Trust and Royal Society grant WT104125AIA & the Bristol Advanced Computing Research Centre (http://www.bris.ac.uk/acrc/) (D.J.L.); Wellcome Trust grant 098051 (Q.A.; C.T.-S. and Y.X.); Wellcome Trust Senior Research Fellowship grant 100719/Z/12/Z (M.G.T.); Young Explorers Grant from the National Geographic Society (8900-11) (C.A.E.); ERC Consolidator Grant 647787 ‘LocalAdaptatio’ (A.Ma.); Program of the RAS Presidium “Basic research for the development of the Russian Arctic” (B.M.); Russian Foundation for Basic Research grant 16-06-00303 (E.B.); a Rutherford Fellowship (RDF-10-MAU-001) from the Royal Society of New Zealand (M.P.C.)

P127

To determine diagnostic importance of DNA methylation in patients with chronic atrophic gastritis and induction of “Correa” cascade for gastric cancer prevention. Material and methods: This present study included 80 patients with chronic atrophic gastritis associated with Helicobacter pylori. Diagnoses were confirmed by endoscopic, morphologic, serologic examinations. Age of patients varied from 17 to 78 years old. There were 52 (65%) males and 28 (35%) females. The control group consisted of 32 patients with morphological verified diagnosis of stage I–II gastric cancer. Examination with the purpose to determine hypermethylation of DNA was performed simultaneously in biopsy materials and blood plasma. Provoking factors of hypermethylation in 4 tumors’ genes, APE, E-Cadherin, T1MP3, hMLHI were determined by quantitative methylation with use of Polymerase Chain Reaction. To evaluate the level of methylation we compared the analysis’ results of biopsy and blood plasma tests. Blood serum samples and biopsy specimens were collected at diagnosis until the therapy is started. All patients with chronic atrophic gastritis infected with H. pylori underwent anti-H. pylori therapy according to the protocol. Chronic atrophic gastritis was found at morphologic examination in 40 (50%) patients according to “Correa” cascade. 36 (45%) patients had intestinal metaplasia, and 4 (5%) patients had dysplasia. Reaction was considered to be positive in cases, when the level of methylation in genes listed above was higher in blood serum than in biopsy materials. Results: High concentrations of methylated APE, T1MP3 and hMLIH in genes were found in blood serum of 8 (10%) patients. In the control group, all 32 patients with gastric cancer had high methylation level in blood serum. In the remaining 72 (90%) patients, no high concentration of DNA methylation was found. After the 2-nd course of anti-H. pylori therapy, patients underwent morphologic and endoscopic examinations according to the protocol. Eradication of H. pylori was determined in 86% patients who received therapy. Intestinal metaplasia decreased from 45% to 25% (20 patients). Mild dysplasia was found in 1.2% of cases. Repeated analysis of methylation level showed its decrease after anti-H. pylori therapy in 4 (50%) out of 8 patients. Conclusion: Genetic tests show that DNA methylation in patients with chronic atrophic gastritis has high diagnostic importance. Anti-H. pylori therapy at the different stages of “Correa” cascade has high level of induction in transforming into non invase gastric cancer

A recent bottleneck of Y chromosome diversity coincides with a global change in culture

Contains fulltext : 153022.pdf (publisher's version ) (Open Access)It is commonly thought that human genetic diversity in non-African populations was shaped primarily by an out-of-Africa dispersal 50-100 thousand yr ago (kya). Here, we present a study of 456 geographically diverse high-coverage Y chromosome sequences, including 299 newly reported samples. Applying ancient DNA calibration, we date the Y-chromosomal most recent common ancestor (MRCA) in Africa at 254 (95% CI 192-307) kya and detect a cluster of major non-African founder haplogroups in a narrow time interval at 47-52 kya, consistent with a rapid initial colonization model of Eurasia and Oceania after the out-of-Africa bottleneck. In contrast to demographic reconstructions based on mtDNA, we infer a second strong bottleneck in Y-chromosome lineages dating to the last 10 ky. We hypothesize that this bottleneck is caused by cultural changes affecting variance of reproductive success among males

Data_Sheet_2_Tomato-made edible COVID-19 vaccine TOMAVAC induces neutralizing IgGs in the blood sera of mice and humans.docx

Plant-based edible vaccines that provide two-layered protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outweigh the currently used parenteral types of vaccines, which predominantly cause a systemic immune response. Here, we engineered and selected a transgenic tomato genotype (TOMAVAC) that stably synthesized an antigenic S1 protein of SARS-CoV-2. Two-course spaced force-feeding of mice with ≈5.4 μg/ml TOMAVAC increased up to 16-fold the synthesis of RBD-specific NAbs in blood serum and the significant induction of S-IgA in intestinal lavage fluid. In a surrogate virus neutralization test, TOMAVAC-induced NAbs had 15–25% viral neutralizing activity. The results suggested early evidence of the immunogenicity and protectivity of TOMAVAC against the coronavirus disease 2019 (COVID-19) infection. Furthermore, we observed a positive trend of statistically significant 1.2-fold (average of +42.28 BAU/ml) weekly increase in NAbs in the volunteers' serum relative to the initial day. No severe side effects were observed, preliminarily supporting the safety of TOMAVAC. With the completion of future large-scale studies, higher-generation TOMAVAC should be a cost-effective, ecologically friendly, and widely applicable novel-generation COVID-19 vaccine, providing two-layered protection against SARS-CoV-2.</p

Data_Sheet_1_Tomato-made edible COVID-19 vaccine TOMAVAC induces neutralizing IgGs in the blood sera of mice and humans.docx

Plant-based edible vaccines that provide two-layered protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outweigh the currently used parenteral types of vaccines, which predominantly cause a systemic immune response. Here, we engineered and selected a transgenic tomato genotype (TOMAVAC) that stably synthesized an antigenic S1 protein of SARS-CoV-2. Two-course spaced force-feeding of mice with ≈5.4 μg/ml TOMAVAC increased up to 16-fold the synthesis of RBD-specific NAbs in blood serum and the significant induction of S-IgA in intestinal lavage fluid. In a surrogate virus neutralization test, TOMAVAC-induced NAbs had 15–25% viral neutralizing activity. The results suggested early evidence of the immunogenicity and protectivity of TOMAVAC against the coronavirus disease 2019 (COVID-19) infection. Furthermore, we observed a positive trend of statistically significant 1.2-fold (average of +42.28 BAU/ml) weekly increase in NAbs in the volunteers' serum relative to the initial day. No severe side effects were observed, preliminarily supporting the safety of TOMAVAC. With the completion of future large-scale studies, higher-generation TOMAVAC should be a cost-effective, ecologically friendly, and widely applicable novel-generation COVID-19 vaccine, providing two-layered protection against SARS-CoV-2.</p

A recent bottleneck of Y chromosome diversity coincides with a global change in culture

© 2015 Karmin et al. It is commonly thought that human genetic diversity in non-African populations was shaped primarily by an out-of-Africa dispersal 50-100 thousand yr ago (kya). Here, we present a study of 456 geographically diverse high-coverage Y chromosome sequences, including 299 newly reported samples. Applying ancient DNA calibration, we date the Y-chromosomal most recent common ancestor (MRCA) in Africa at 254 (95% CI 192-307) kya and detect a cluster of major non-African founder haplogroups in a narrow time interval at 47-52 kya, consistent with a rapid initial colonization model of Eurasia and Oceania after the out-of-Africa bottleneck. In contrast to demographic reconstructions based on mtDNA, we infer a second strong bottleneck in Y-chromosome lineages dating to the last 10 ky. We hypothesize that this bottleneck is caused by cultural changes affecting variance of reproductive success among males