Publications by authors named "Ben Krause-Kyora"

27 Publications

  • Page 1 of 1

Ancient DNA Study in Medieval Europeans Shows an Association Between HLA-DRB1*03 and Paratyphoid Fever.

Front Immunol 2021 15;12:691475. Epub 2021 Jul 15.

Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany.

Outbreaks of infectious diseases repeatedly affected medieval Europe, leaving behind a large number of dead often inhumed in mass graves. Human remains interred in two burial pits from 14 century CE Germany exhibited molecular evidence of Paratyphi C ( Paratyphi C) infection. The pathogen is responsible for paratyphoid fever, which was likely the cause of death for the buried individuals. This finding presented the unique opportunity to conduct a paratyphoid fever association study in a European population. We focused on HLA-DRB1*03:01 that is a known risk allele for enteric fever in present-day South Asians. We generated HLA profiles for 29 medieval Paratyphi C cases and 24 contemporaneous controls and compared these to a modern German population. The frequency of the risk allele was higher in the medieval cases (29.6%) compared to the contemporaneous controls (13%; ), albeit not significantly so, possibly because of small sample sizes. Indeed, in comparison with the modern controls (; 10.2%; ) the frequency difference became statistically significant. This comparison also suggested a slight decrease in the allele's prevalence between the medieval and modern controls. Up to now, this is the first study on the genetic predisposition to infection in Europeans and the only association analysis on paratyphoid fever C. Functional investigation using computational binding prediction between HLA variants and Paratyphi and Typhi peptides supported a reduced recognition capacity of bacterial proteins by DRB1*03:01 relative to other common DRB1 variants. This pattern could potentially explain the disease association. Our results suggest a slightly reduced predisposition to paratyphoid fever in modern Europeans. The causative allele, however, is still common today, which can be explained by a trade-off, as DRB1*03:01 is protective against infectious respiratory diseases such as severe respiratory syndrome (SARS). It is thus possible that the allele also provided resistance to corona-like viruses in the past.
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http://dx.doi.org/10.3389/fimmu.2021.691475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320744PMC
October 2021

A 5,000-year-old hunter-gatherer already plagued by Yersinia pestis.

Cell Rep 2021 06;35(13):109278

Institute of Clinical Molecular Biology, Kiel University, Rosalind-Franklin-Str. 12, 24105 Kiel, Germany. Electronic address:

A 5,000-year-old Yersinia pestis genome (RV 2039) is reconstructed from a hunter-fisher-gatherer (5300-5050 cal BP) buried at Riņņukalns, Latvia. RV 2039 is the first in a series of ancient strains that evolved shortly after the split of Y. pestis from its antecessor Y. pseudotuberculosis ∼7,000 years ago. The genomic and phylogenetic characteristics of RV 2039 are consistent with the hypothesis that this very early Y. pestis form was most likely less transmissible and maybe even less virulent than later strains. Our data do not support the scenario of a prehistoric pneumonic plague pandemic, as suggested previously for the Neolithic decline. The geographical and temporal distribution of the few prehistoric Y. pestis cases reported so far is more in agreement with single zoonotic events.
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http://dx.doi.org/10.1016/j.celrep.2021.109278DOI Listing
June 2021

Analysis of Genomic DNA from Medieval Plague Victims Suggests Long-Term Effect of Yersinia pestis on Human Immunity Genes.

Mol Biol Evol 2021 Sep;38(10):4059-4076

Max Planck Institute for the Science of Human History, Jena, Germany.

Pathogens and associated outbreaks of infectious disease exert selective pressure on human populations, and any changes in allele frequencies that result may be especially evident for genes involved in immunity. In this regard, the 1346-1353 Yersinia pestis-caused Black Death pandemic, with continued plague outbreaks spanning several hundred years, is one of the most devastating recorded in human history. To investigate the potential impact of Y. pestis on human immunity genes, we extracted DNA from 36 plague victims buried in a mass grave in Ellwangen, Germany in the 16th century. We targeted 488 immune-related genes, including HLA, using a novel in-solution hybridization capture approach. In comparison with 50 modern native inhabitants of Ellwangen, we find differences in allele frequencies for variants of the innate immunity proteins Ficolin-2 and NLRP14 at sites involved in determining specificity. We also observed that HLA-DRB1*13 is more than twice as frequent in the modern population, whereas HLA-B alleles encoding an isoleucine at position 80 (I-80+), HLA C*06:02 and HLA-DPB1 alleles encoding histidine at position 9 are half as frequent in the modern population. Simulations show that natural selection has likely driven these allele frequency changes. Thus, our data suggest that allele frequencies of HLA genes involved in innate and adaptive immunity responsible for extracellular and intracellular responses to pathogenic bacteria, such as Y. pestis, could have been affected by the historical epidemics that occurred in Europe.
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http://dx.doi.org/10.1093/molbev/msab147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476174PMC
September 2021

Mass burial genomics reveals outbreak of enteric paratyphoid fever in the Late Medieval trade city Lübeck.

iScience 2021 May 20;24(5):102419. Epub 2021 Apr 20.

Institute of Clinical Molecular Biology, Kiel University, 24105 Kiel, Germany.

Medieval Europe was repeatedly affected by outbreaks of infectious diseases, some of which reached epidemic proportions. A Late Medieval mass burial next to the Heiligen-Geist-Hospital in Lübeck (present-day Germany) contained the skeletal remains of more than 800 individuals who had presumably died from infectious disease. From 92 individuals, we screened the ancient DNA extracts for the presence of pathogens to determine the cause of death. Metagenomic analysis revealed evidence of subsp. serovar Paratyphi C, suggesting an outbreak of enteric paratyphoid fever. Three reconstructed . Paratyphi C genomes showed close similarity to a strain from Norway (1200 CE). Radiocarbon dates placed the disease outbreak in Lübeck between 1270 and 1400 cal CE, with historical records indicating 1367 CE as the most probable year. The deceased were of northern and eastern European descent, confirming Lübeck as an important trading center of the Hanseatic League in the Baltic region.
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http://dx.doi.org/10.1016/j.isci.2021.102419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100618PMC
May 2021

Phylogeography in an "oyster" shell provides first insights into the genetic structure of an extinct Ostrea edulis population.

Sci Rep 2021 01 27;11(1):2307. Epub 2021 Jan 27.

Institut für klinische Molekularbiologie (IKMB), Christian-Albrechts-Universität zu Kiel, 24118, Kiel, Germany.

The historical phylogeography of Ostrea edulis was successfully depicted in its native range for the first time using ancient DNA methods on dry shells from museum collections. This research reconstructed the historical population structure of the European flat oyster across Europe in the 1870s-including the now extinct population in the Wadden Sea. In total, four haplogroups were identified with one haplogroup having a patchy distribution from the North Sea to the Atlantic coast of France. This irregular distribution could be the result of translocations. The other three haplogroups are restricted to narrow geographic ranges, which may indicate adaptation to local environmental conditions or geographical barriers to gene flow. The phylogenetic reconstruction of the four haplogroups suggests the signatures of glacial refugia and postglacial expansion. The comparison with present-day O. edulis populations revealed a temporally stable population genetic pattern over the past 150 years despite large-scale translocations. This historical phylogeographic reconstruction was able to discover an autochthonous population in the German and Danish Wadden Sea in the late nineteenth century, where O. edulis is extinct today. The genetic distinctiveness of a now-extinct population hints at a connection between the genetic background of O. edulis in the Wadden Sea and for its absence until today.
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http://dx.doi.org/10.1038/s41598-021-82020-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840910PMC
January 2021

Genome-wide study of a Neolithic Wartberg grave community reveals distinct HLA variation and hunter-gatherer ancestry.

Commun Biol 2021 01 25;4(1):113. Epub 2021 Jan 25.

Institute of Clinical Molecular Biology, Kiel University, Rosalind-Franklin-Strasse 12, 24105, Kiel, Germany.

The Wartberg culture (WBC, 3500-2800 BCE) dates to the Late Neolithic period, a time of important demographic and cultural transformations in western Europe. We performed genome-wide analyses of 42 individuals who were interred in a WBC collective burial in Niedertiefenbach, Germany (3300-3200 cal. BCE). The results showed that the farming population of Niedertiefenbach carried a surprisingly large hunter-gatherer ancestry component (34-58%). This component was most likely introduced during the cultural transformation that led to the WBC. In addition, the Niedertiefenbach individuals exhibited a distinct human leukocyte antigen gene pool, possibly reflecting an immune response that was geared towards detecting viral infections.
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http://dx.doi.org/10.1038/s42003-020-01627-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835224PMC
January 2021

Comparison of target enrichment strategies for ancient pathogen DNA.

Biotechniques 2020 12 2;69(6):455-459. Epub 2020 Nov 2.

Institute for Archaeological Sciences, Archaeo- & Palaeogenetics, University of Tübingen, 72070 Tübingen, Germany.

In ancient DNA research, the degraded nature of the samples generally results in poor yields of highly fragmented DNA; targeted DNA enrichment is thus required to maximize research outcomes. The three commonly used methods - array-based hybridization capture and in-solution capture using either RNA or DNA baits - have different characteristics that may influence the capture efficiency, specificity and reproducibility. Here we compare their performance in enriching pathogen DNA of and from 11 ancient and 19 modern samples. We find that in-solution approaches are the most effective method in ancient and modern samples of both pathogens and that RNA baits usually perform better than DNA baits.
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http://dx.doi.org/10.2144/btn-2020-0100DOI Listing
December 2020

Yersinia pestis strains from Latvia show depletion of the pla virulence gene at the end of the second plague pandemic.

Sci Rep 2020 09 3;10(1):14628. Epub 2020 Sep 3.

Institute of Clinical Molecular Biology, Kiel University, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.

Ancient genomic studies have identified Yersinia pestis (Y. pestis) as the causative agent of the second plague pandemic (fourteenth-eighteenth century) that started with the Black Death (1,347-1,353). Most of the Y. pestis strains investigated from this pandemic have been isolated from western Europe, and not much is known about the diversity and microevolution of this bacterium in eastern European countries. In this study, we investigated human remains excavated from two cemeteries in Riga (Latvia). Historical evidence suggests that the burials were a consequence of plague outbreaks during the seventeenth century. DNA was extracted from teeth of 16 individuals and subjected to shotgun sequencing. Analysis of the metagenomic data revealed the presence of Y. pestis sequences in four remains, confirming that the buried individuals were victims of plague. In two samples, Y. pestis DNA coverage was sufficient for genome reconstruction. Subsequent phylogenetic analysis showed that the Riga strains fell within the diversity of the already known post-Black Death genomes. Interestingly, the two Latvian isolates did not cluster together. Moreover, we detected a drop in coverage of the pPCP1 plasmid region containing the pla gene. Further analysis indicated the presence of two pPCP1 plasmids, one with and one without the pla gene region, and only one bacterial chromosome, indicating that the same bacterium carried two distinct pPCP1 plasmids. In addition, we found the same pattern in the majority of previously published post-Black Death strains, but not in the Black Death strains. The pla gene is an important virulence factor for the infection of and transmission in humans. Thus, the spread of pla-depleted strains may, among other causes, have contributed to the disappearance of the second plague pandemic in eighteenth century Europe.
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http://dx.doi.org/10.1038/s41598-020-71530-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471286PMC
September 2020

High mitochondrial diversity of domesticated goats persisted among Bronze and Iron Age pastoralists in the Inner Asian Mountain Corridor.

PLoS One 2020 21;15(5):e0233333. Epub 2020 May 21.

Graduate School "Human Development in Landscapes", Kiel University, Kiel, Germany.

Goats were initially managed in the Near East approximately 10,000 years ago and spread across Eurasia as economically productive and environmentally resilient herd animals. While the geographic origins of domesticated goats (Capra hircus) in the Near East have been long-established in the zooarchaeological record and, more recently, further revealed in ancient genomes, the precise pathways by which goats spread across Asia during the early Bronze Age (ca. 3000 to 2500 cal BC) and later remain unclear. We analyzed sequences of hypervariable region 1 and cytochrome b gene in the mitochondrial genome (mtDNA) of goats from archaeological sites along two proposed transmission pathways as well as geographically intermediary sites. Unexpectedly high genetic diversity was present in the Inner Asian Mountain Corridor (IAMC), indicated by mtDNA haplotypes representing common A lineages and rarer C and D lineages. High mtDNA diversity was also present in central Kazakhstan, while only mtDNA haplotypes of lineage A were observed from sites in the Northern Eurasian Steppe (NES). These findings suggest that herding communities living in montane ecosystems were drawing from genetically diverse goat populations, likely sourced from communities in the Iranian Plateau, that were sustained by repeated interaction and exchange. Notably, the mitochondrial genetic diversity associated with goats of the IAMC also extended into the semi-arid region of central Kazakhstan, while NES communities had goats reflecting an isolated founder population, possibly sourced via eastern Europe or the Caucasus region.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233333PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241827PMC
August 2020

Targeted analysis of polymorphic loci from low-coverage shotgun sequence data allows accurate genotyping of HLA genes in historical human populations.

Sci Rep 2020 04 30;10(1):7339. Epub 2020 Apr 30.

Research Group for Evolutionary Immunogenomics, Max Planck Institute for Evolutionary Biology, 24306, Ploen, Germany.

The highly polymorphic human leukocyte antigen (HLA) plays a crucial role in adaptive immunity and is associated with various complex diseases. Accurate analysis of HLA genes using ancient DNA (aDNA) data is crucial for understanding their role in human adaptation to pathogens. Here, we describe the TARGT pipeline for targeted analysis of polymorphic loci from low-coverage shotgun sequence data. The pipeline was successfully applied to medieval aDNA samples and validated using both simulated aDNA and modern empirical sequence data from the 1000 Genomes Project. Thus the TARGT pipeline enables accurate analysis of HLA polymorphisms in historical (and modern) human populations.
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http://dx.doi.org/10.1038/s41598-020-64312-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193575PMC
April 2020

Gene-flow from steppe individuals into Cucuteni-Trypillia associated populations indicates long-standing contacts and gradual admixture.

Sci Rep 2020 03 6;10(1):4253. Epub 2020 Mar 6.

Institute of Clinical Molecular Biology, Kiel University, Kiel, Germany.

The Cucuteni-Trypillia complex (CTC) flourished in eastern Europe for over two millennia (5100-2800 BCE) from the end of the Neolithic to the Early Bronze Age. Its vast distribution area encompassed modern-day eastern Romania, Moldova and western/central Ukraine. Due to a lack of existing burials throughout most of this time, only little is known about the people associated with this complex and their genetic composition. Here, we present genome-wide data generated from the skeletal remains of four females that were excavated from two Late CTC sites in Moldova (3500-3100 BCE). All individuals carried a large Neolithic-derived ancestry component and were genetically more closely related to Linear Pottery than to Anatolian farmers. Three of the specimens also showed considerable amounts of steppe-related ancestry, suggesting influx into the CTC gene-pool from people affiliated with, for instance, the Ukraine Mesolithic. The latter scenario is supported by archaeological evidence. Taken together, our results confirm that the steppe component arrived in eastern Europe farming communities maybe as early as 3500 BCE. In addition, they are in agreement with the hypothesis of ongoing contacts and gradual admixture between incoming steppe and local western populations.
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http://dx.doi.org/10.1038/s41598-020-61190-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060214PMC
March 2020

Coming and going - Historical distributions of the European oyster Ostrea edulis Linnaeus, 1758 and the introduced slipper limpet Crepidula fornicata Linnaeus, 1758 in the North Sea.

PLoS One 2019 24;14(10):e0224249. Epub 2019 Oct 24.

Zoological Museum, Christian-Albrechts-University, Kiel, Schleswig-Holstein, Germany.

Natural history collections are fundamental for biodiversity research as well as for any applied environment-related research. These collections can be seen as archives of earth´s life providing the basis to address highly relevant scientific questions such as how biodiversity changes in certain environments, either through evolutionary processes in a geological timescale, or by man-made transformation of habitats throughout the last decades and/or centuries. A prominent example is the decline of the European flat oyster Ostrea edulis Linneaus, 1758 in the North Sea and the concomitant invasion of the common limpet slipper Crepidula fornicata, which has been implicated to have negative effects on O. edulis. We used collections to analyse population changes in both species in the North Sea. In order to reconstruct the change in distribution and diversity over the past 200 years, we combined the temporal and spatial information recorded with the collected specimens contained in several European natural history collections. Our data recover the decline of O. edulis in the North Sea from the 19th century to the present and the process of invasion of C. fornicata. Importantly, the decline of O. edulis was nearly completed before C. fornicata appeared in the North Sea, suggesting that the latter had nothing to do with the local extinction of O. edulis in the North Sea.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224249PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812771PMC
March 2020

Radiocarbon dating and isotope analysis on the purported Aurignacian skeletal remains from Fontana Nuova (Ragusa, Italy).

PLoS One 2019 20;14(3):e0213173. Epub 2019 Mar 20.

Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.

Proving voyaging at sea by Palaeolithic humans is a difficult archaeological task, even for short distances. In the Mediterranean, a commonly accepted sea crossing is that from the Italian Peninsula to Sicily by anatomically modern humans, purportedly of the Aurignacian culture. This claim, however, was only supported by the typological attribution to the Aurignacian of the lithic industries from the insular site of Fontana Nuova. AMS radiocarbon dating undertaken as part of our research shows that the faunal remains, previously considered Aurignacian, actually date to the Holocene. Absolute dating on dentinal collagen also attributes the human teeth from the site to the early Holocene, although we were unable to obtain ancient DNA to evaluate their ancestry. Ten radiocarbon dates on human and other taxa are comprised between 9910-9700 cal. BP and 8600-8480 cal. BP, indicating that Fontana Nuova was occupied by Mesolithic and not Aurignacian hunter-gatherers. Only a new study of the lithic assemblage could establish if the material from Fontana Nuova is a mixed collection that includes both late Upper Palaeolithic (Epigravettian) and Mesolithic artefacts, as can be suggested by taking into account both the results of our study and of the most recent reinterpretation of the lithics. Nevertheless, this research suggests that the notion that Aurignacian groups were present in Sicily should now be revised. Another outcome of our study is that we found that three specimens, attributed on grounds both of morphological and ZooMS identifications to Cervus elaphus, had δ13C values significantly higher than any available for such species in Europe.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213173PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6426221PMC
November 2019

The Iceman's Last Meal Consisted of Fat, Wild Meat, and Cereals.

Curr Biol 2018 07 12;28(14):2348-2355.e9. Epub 2018 Jul 12.

SLING, Life Sciences Institute, National University of Singapore, Singapore; Department of Biochemistry, National University of Singapore, Singapore.

The history of humankind is marked by the constant adoption of new dietary habits affecting human physiology, metabolism, and even the development of nutrition-related disorders. Despite clear archaeological evidence for the shift from hunter-gatherer lifestyle to agriculture in Neolithic Europe [1], very little information exists on the daily dietary habits of our ancestors. By undertaking a complementary -omics approach combined with microscopy, we analyzed the stomach content of the Iceman, a 5,300-year-old European glacier mummy [2, 3]. He seems to have had a remarkably high proportion of fat in his diet, supplemented with fresh or dried wild meat, cereals, and traces of toxic bracken. Our multipronged approach provides unprecedented analytical depth, deciphering the nutritional habit, meal composition, and food-processing methods of this Copper Age individual.
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http://dx.doi.org/10.1016/j.cub.2018.05.067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065529PMC
July 2018

Draft Genome Sequence of Riemerella anatipestifer Isolate 17CS0503.

Genome Announc 2018 May 17;6(20). Epub 2018 May 17.

Institute of Bacterial Infections and Zoonoses at the Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Jena, Germany.

is a Gram-negative bacterium belonging to the family It is primarily associated with acute septicemia in younger birds. The isolate 17CS0503 described here was isolated from a Peking duck () in Hannover, Germany, in 1999.
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http://dx.doi.org/10.1128/genomeA.00274-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958266PMC
May 2018

Ancient genomes reveal a high diversity of Mycobacterium leprae in medieval Europe.

PLoS Pathog 2018 05 10;14(5):e1006997. Epub 2018 May 10.

Institute for Archaeological Sciences, University of Tübingen, Tübingen, Germany.

Studying ancient DNA allows us to retrace the evolutionary history of human pathogens, such as Mycobacterium leprae, the main causative agent of leprosy. Leprosy is one of the oldest recorded and most stigmatizing diseases in human history. The disease was prevalent in Europe until the 16th century and is still endemic in many countries with over 200,000 new cases reported annually. Previous worldwide studies on modern and European medieval M. leprae genomes revealed that they cluster into several distinct branches of which two were present in medieval Northwestern Europe. In this study, we analyzed 10 new medieval M. leprae genomes including the so far oldest M. leprae genome from one of the earliest known cases of leprosy in the United Kingdom-a skeleton from the Great Chesterford cemetery with a calibrated age of 415-545 C.E. This dataset provides a genetic time transect of M. leprae diversity in Europe over the past 1500 years. We find M. leprae strains from four distinct branches to be present in the Early Medieval Period, and strains from three different branches were detected within a single cemetery from the High Medieval Period. Altogether these findings suggest a higher genetic diversity of M. leprae strains in medieval Europe at various time points than previously assumed. The resulting more complex picture of the past phylogeography of leprosy in Europe impacts current phylogeographical models of M. leprae dissemination. It suggests alternative models for the past spread of leprosy such as a wide spread prevalence of strains from different branches in Eurasia already in Antiquity or maybe even an origin in Western Eurasia. Furthermore, these results highlight how studying ancient M. leprae strains improves understanding the history of leprosy worldwide.
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http://dx.doi.org/10.1371/journal.ppat.1006997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5944922PMC
May 2018

Neolithic and medieval virus genomes reveal complex evolution of hepatitis B.

Elife 2018 05 10;7. Epub 2018 May 10.

Max Planck Institute for the Science of Human History, Jena, Germany.

The hepatitis B virus (HBV) is one of the most widespread human pathogens known today, yet its origin and evolutionary history are still unclear and controversial. Here, we report the analysis of three ancient HBV genomes recovered from human skeletons found at three different archaeological sites in Germany. We reconstructed two Neolithic and one medieval HBV genome by assembly from shotgun DNA sequencing data. Additionally, we observed HBV-specific peptides using paleo-proteomics. Our results demonstrated that HBV has circulated in the European population for at least 7000 years. The Neolithic HBV genomes show a high genomic similarity to each other. In a phylogenetic network, they do not group with any human-associated HBV genome and are most closely related to those infecting African non-human primates. The ancient viruses appear to represent distinct lineages that have no close relatives today and possibly went extinct. Our results reveal the great potential of ancient DNA from human skeletons in order to study the long-time evolution of blood borne viruses.
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http://dx.doi.org/10.7554/eLife.36666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6008052PMC
May 2018

Ancient DNA study reveals HLA susceptibility locus for leprosy in medieval Europeans.

Nat Commun 2018 05 1;9(1):1569. Epub 2018 May 1.

Institute of Clinical Molecular Biology, Kiel University, Kiel, 24105, Germany.

Leprosy, a chronic infectious disease caused by Mycobacterium leprae (M. leprae), was very common in Europe till the 16th century. Here, we perform an ancient DNA study on medieval skeletons from Denmark that show lesions specific for lepromatous leprosy (LL). First, we test the remains for M. leprae DNA to confirm the infection status of the individuals and to assess the bacterial diversity. We assemble 10 complete M. leprae genomes that all differ from each other. Second, we evaluate whether the human leukocyte antigen allele DRB1*15:01, a strong LL susceptibility factor in modern populations, also predisposed medieval Europeans to the disease. The comparison of genotype data from 69 M. leprae DNA-positive LL cases with those from contemporary and medieval controls reveals a statistically significant association in both instances. In addition, we observe that DRB1*15:01 co-occurs with DQB1*06:02 on a haplotype that is a strong risk factor for inflammatory diseases today.
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http://dx.doi.org/10.1038/s41467-018-03857-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5931558PMC
May 2018

The genomic history of southeastern Europe.

Nature 2018 03 21;555(7695):197-203. Epub 2018 Feb 21.

Dipartimento di Biologia, Università di Firenze, 50122 Florence, Italy.

Farming was first introduced to Europe in the mid-seventh millennium bc, and was associated with migrants from Anatolia who settled in the southeast before spreading throughout Europe. Here, to understand the dynamics of this process, we analysed genome-wide ancient DNA data from 225 individuals who lived in southeastern Europe and surrounding regions between 12000 and 500 bc. We document a west-east cline of ancestry in indigenous hunter-gatherers and, in eastern Europe, the early stages in the formation of Bronze Age steppe ancestry. We show that the first farmers of northern and western Europe dispersed through southeastern Europe with limited hunter-gatherer admixture, but that some early groups in the southeast mixed extensively with hunter-gatherers without the sex-biased admixture that prevailed later in the north and west. We also show that southeastern Europe continued to be a nexus between east and west after the arrival of farmers, with intermittent genetic contact with steppe populations occurring up to 2,000 years earlier than the migrations from the steppe that ultimately replaced much of the population of northern Europe.
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http://dx.doi.org/10.1038/nature25778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6091220PMC
March 2018

Publisher Correction: Identification and characterization of two functional variants in the human longevity gene FOXO3.

Nat Commun 2018 01 17;9(1):320. Epub 2018 Jan 17.

Department of Statistical Genetics and Bioinformatics, Cologne Center for Genomics, University of Cologne, Weyertal 115b, 50931, Cologne, Germany.

The original version of this Article contained an error in the spelling of the author Robert Häsler, which was incorrectly given as Robert Häesler. This has now been corrected in both the PDF and HTML versions of the Article.
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http://dx.doi.org/10.1038/s41467-018-02842-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770466PMC
January 2018

Identification and characterization of two functional variants in the human longevity gene FOXO3.

Nat Commun 2017 12 12;8(1):2063. Epub 2017 Dec 12.

Institute of Clinical Molecular Biology, Kiel University, University Hospital Schleswig-Holstein, Campus Kiel, Rosalind-Franklin-Straße 12, 24105, Kiel, Germany.

FOXO3 is consistently annotated as a human longevity gene. However, functional variants and underlying mechanisms for the association remain unknown. Here, we perform resequencing of the FOXO3 locus and single-nucleotide variant (SNV) genotyping in three European populations. We find two FOXO3 SNVs, rs12206094 and rs4946935, to be most significantly associated with longevity and further characterize them functionally. We experimentally validate the in silico predicted allele-dependent binding of transcription factors (CTCF, SRF) to the SNVs. Specifically, in luciferase reporter assays, the longevity alleles of both variants show considerable enhancer activities that are reversed by IGF-1 treatment. An eQTL database search reveals that the alleles are also associated with higher FOXO3 mRNA expression in various human tissues, which is in line with observations in long-lived model organisms. In summary, we present experimental evidence for a functional link between common intronic variants in FOXO3 and human longevity.
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http://dx.doi.org/10.1038/s41467-017-02183-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727304PMC
December 2017

Insights into early pig domestication provided by ancient DNA analysis.

Sci Rep 2017 03 16;7:44550. Epub 2017 Mar 16.

Institute of Clinical Molecular Biology, Kiel University, 24105 Kiel, Germany.

Pigs (Sus scrofa) were first domesticated between 8,500 and 8,000 cal BC in the Near East, from where they were subsequently brought into Europe by agriculturalists. Soon after the arrival of the first domestic pigs in northern Europe (~4500 BC), farmers are thought to have started to incorporate local wild boars into their swine herds. This husbandry strategy ultimately resulted in the domestication of European wild boars. Here, we set out to provide a more precise geographic and temporal framework of the early management of suid populations in northern Europe, drawing upon mitochondrial DNA haplotype data from 116 Neolithic Sus specimens. We developed a quantitative mathematical model tracing the haplotypes of the domestic pigs back to their most likely geographic origin. Our modelling results suggest that, between 5000 and 4000 BC, almost all matrilines in the north originated from domesticated animals from the south of central Europe. In the following period (4000-3000 BC), an estimated 78-100% of domesticates in the north were of northern matrilineal origin, largely from local wild boars. These findings point towards a dramatic change in suid management strategies taking place throughout south-central and northern Europe after 4000 BC.
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http://dx.doi.org/10.1038/srep44550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5353713PMC
March 2017

The 5300-year-old Helicobacter pylori genome of the Iceman.

Science 2016 Jan;351(6269):162-165

Institute for Mummies and the Iceman, EURAC research, Viale Druso 1, 39100 Bolzano, Italy.

The stomach bacterium Helicobacter pylori is one of the most prevalent human pathogens. It has dispersed globally with its human host, resulting in a distinct phylogeographic pattern that can be used to reconstruct both recent and ancient human migrations. The extant European population of H. pylori is known to be a hybrid between Asian and African bacteria, but there exist different hypotheses about when and where the hybridization took place, reflecting the complex demographic history of Europeans. Here, we present a 5300-year-old H. pylori genome from a European Copper Age glacier mummy. The "Iceman" H. pylori is a nearly pure representative of the bacterial population of Asian origin that existed in Europe before hybridization, suggesting that the African population arrived in Europe within the past few thousand years.
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http://dx.doi.org/10.1126/science.aad2545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4775254PMC
January 2016

Use of domesticated pigs by Mesolithic hunter-gatherers in northwestern Europe.

Nat Commun 2013 ;4:2348

Institute of Clinical Molecular Biology, Christian-Albrechts-University, 24105 Kiel, Germany.

Mesolithic populations throughout Europe used diverse resource exploitation strategies that focused heavily on collecting and hunting wild prey. Between 5500 and 4200 cal BC, agriculturalists migrated into northwestern Europe bringing a suite of Neolithic technologies including domesticated animals. Here we investigate to what extent Mesolithic Ertebølle communities in northern Germany had access to domestic pigs, possibly through contact with neighbouring Neolithic agricultural groups. We employ a multidisciplinary approach, applying sequencing of ancient mitochondrial and nuclear DNA (coat colour-coding gene MC1R) as well as traditional and geometric morphometric (molar size and shape) analyses in Sus specimens from 17 Neolithic and Ertebølle sites. Our data from 63 ancient pig specimens show that Ertebølle hunter-gatherers acquired domestic pigs of varying size and coat colour that had both Near Eastern and European mitochondrial DNA ancestry. Our results also reveal that domestic pigs were present in the region ~500 years earlier than previously demonstrated.
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http://dx.doi.org/10.1038/ncomms3348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3903269PMC
April 2014

Genome-wide comparison of medieval and modern Mycobacterium leprae.

Science 2013 Jul 13;341(6142):179-83. Epub 2013 Jun 13.

Institute for Archaeological Sciences, University of Tübingen, 72070 Tübingen, Germany.

Leprosy was endemic in Europe until the Middle Ages. Using DNA array capture, we have obtained genome sequences of Mycobacterium leprae from skeletons of five medieval leprosy cases from the United Kingdom, Sweden, and Denmark. In one case, the DNA was so well preserved that full de novo assembly of the ancient bacterial genome could be achieved through shotgun sequencing alone. The ancient M. leprae sequences were compared with those of 11 modern strains, representing diverse genotypes and geographic origins. The comparisons revealed remarkable genomic conservation during the past 1000 years, a European origin for leprosy in the Americas, and the presence of an M. leprae genotype in medieval Europe now commonly associated with the Middle East. The exceptional preservation of M. leprae biomarkers, both DNA and mycolic acids, in ancient skeletons has major implications for palaeomicrobiology and human pathogen evolution.
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http://dx.doi.org/10.1126/science.1238286DOI Listing
July 2013

STR-typing of ancient skeletal remains: which multiplex-PCR kit is the best?

Croat Med J 2012 Oct;53(5):416-22

Institute of Legal Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Arnold-Heller-Strasse 12, Kiel, Germany.

Aim: To comparatively test nine co mmercially available short tandem repeat (STR)-multiplex kits (PowerPlex 16, 16HS, ES, ESI17, ESX17, S5 [all Promega]; AmpFiSTR Identifiler, NGM and SEfiler [all Applied Biosystems]) for their efficiency and applicability to analyze ancient and thus highly degraded DNA samples.

Methods: Fifteen human skeletal remains from the late medieval age were obtained and analyzed using the nine polymerase chain reaction assays with slightly modified protocols. Data were systematically compared to find the most meaningful and sensitive assay.

Results: The ESI, ESX, and NGM kits showed the best overall results regarding amplification success, detection rate, identification of heterozygous alleles, sex determination, and reproducibility of the obtained data.

Conclusion: Since application of these three kits enables the employment of different primer sequences for all the investigated amplicons, a combined application is recommended for best possible and--most importantly--reliable genetic analysis of ancient skeletal material or otherwise highly degraded samples, e.g., from forensic cases.
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http://dx.doi.org/10.3325/cmj.2012.53.416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494155PMC
October 2012

Emerging genetic patterns of the European Neolithic: perspectives from a late Neolithic Bell Beaker burial site in Germany.

Am J Phys Anthropol 2012 Aug 3;148(4):571-9. Epub 2012 May 3.

Graduate School "Human Development in Landscapes," Christian-Albrechts-University of Kiel, Germany.

The transition from hunting and gathering to agriculture in Europe is associated with demographic changes that may have shifted the human gene pool of the region as a result of an influx of Neolithic farmers from the Near East. However, the genetic composition of populations after the earliest Neolithic, when a diverse mosaic of societies that had been fully engaged in agriculture for some time appeared in central Europe, is poorly known. At this period during the Late Neolithic (ca. 2,800-2,000 BC), regionally distinctive burial patterns associated with two different cultural groups emerge, Bell Beaker and Corded Ware, and may reflect differences in how these societies were organized. Ancient DNA analyses of human remains from the Late Neolithic Bell Beaker site of Kromsdorf, Germany showed distinct mitochondrial haplotypes for six individuals, which were classified under the haplogroups I1, K1, T1, U2, U5, and W5, and two males were identified as belonging to the Y haplogroup R1b. In contrast to other Late Neolithic societies in Europe emphasizing maintenance of biological relatedness in mortuary contexts, the diversity of maternal haplotypes evident at Kromsdorf suggests that burial practices of Bell Beaker communities operated outside of social norms based on shared maternal lineages. Furthermore, our data, along with those from previous studies, indicate that modern U5-lineages may have received little, if any, contribution from the Mesolithic or Neolithic mitochondrial gene pool.
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http://dx.doi.org/10.1002/ajpa.22074DOI Listing
August 2012
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