Publications by authors named "Frank Maixner"

46 Publications

The Lady from Basel's Barfüsserkirche - Molecular confirmation of the Mummy's identity through mitochondrial DNA of living relatives spanning 22 generations.

Forensic Sci Int Genet 2021 Oct 9;56:102604. Epub 2021 Oct 9.

Institute for Mummy Studies, Eurac Research, Drususallee/Viale Druso 1, 39100 Bozen, Bolzano, Italy.

The identity of the mummified Lady from the Barfüsser Church in Basel, Switzerland has been unsolved for decades, despite the prominent location of the burial place in front of the choir screen. A recent multidisciplinary research approach came up with a possible candidate, Anna Catharina Bischoff who died in Basel in 1787 with an age of 69 years (1719-1787). To verify the identity of the mummy, genealogists of the Citizen Science Basel discovered three living individuals of the maternal lineage of two different family branches, separated from Anna Catharina Bischoff by up to 22 generations. In this study we compare the ancient mitochondrial DNA of the mummy recovered from a premolar to the mitochondrial DNA of these three candidates. Initially the mitochondrial hypervariable regions I and II of the living individuals were screened using the Sanger sequencing method. This was followed by a mitochondrial capture approach and next generation sequencing to enrich for the whole mitochondrial genome of the mummy and one living person. A full mitochondrial genome has been recovered of both individuals sharing an identical haplotype. The sequence was assigned to the mitochondrial haplogroup U5a1+!16192 including two private mutations 10006G and 16293C. Only by using an interdisciplinary approach combining ancient DNA analysis and genealogy a maternal lineage of a non-noble family spanning 22 generations could be confirmed.
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http://dx.doi.org/10.1016/j.fsigen.2021.102604DOI Listing
October 2021

Hallstatt miners consumed blue cheese and beer during the Iron Age and retained a non-Westernized gut microbiome until the Baroque period.

Curr Biol 2021 Oct 8. Epub 2021 Oct 8.

Prehistoric Department, Museum of Natural History Vienna, Burgring 7, 1010 Vienna, Austria. Electronic address:

We subjected human paleofeces dating from the Bronze Age to the Baroque period (18 century AD) to in-depth microscopic, metagenomic, and proteomic analyses. The paleofeces were preserved in the underground salt mines of the UNESCO World Heritage site of Hallstatt in Austria. This allowed us to reconstruct the diet of the former population and gain insights into their ancient gut microbiome composition. Our dietary survey identified bran and glumes of different cereals as some of the most prevalent plant fragments. This highly fibrous, carbohydrate-rich diet was supplemented with proteins from broad beans and occasionally with fruits, nuts, or animal food products. Due to these traditional dietary habits, all ancient miners up to the Baroque period have gut microbiome structures akin to modern non-Westernized individuals whose diets are also mainly composed of unprocessed foods and fresh fruits and vegetables. This may indicate a shift in the gut community composition of modern Westernized populations due to quite recent dietary and lifestyle changes. When we extended our microbial survey to fungi present in the paleofeces, in one of the Iron Age samples, we observed a high abundance of Penicillium roqueforti and Saccharomyces cerevisiae DNA. Genome-wide analysis indicates that both fungi were involved in food fermentation and provides the first molecular evidence for blue cheese and beer consumption in Iron Age Europe.
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http://dx.doi.org/10.1016/j.cub.2021.09.031DOI Listing
October 2021

Metagenomic analysis of ancient dental calculus reveals unexplored diversity of oral archaeal Methanobrevibacter.

Microbiome 2021 09 30;9(1):197. Epub 2021 Sep 30.

Institute for Mummy Studies, Eurac Research, 39100, Bolzano, Italy.

Background: Dental calculus (mineralised dental plaque) preserves many types of microfossils and biomolecules, including microbial and host DNA, and ancient calculus are thus an important source of information regarding our ancestral human oral microbiome. In this study, we taxonomically characterised the dental calculus microbiome from 20 ancient human skeletal remains originating from Trentino-South Tyrol, Italy, dating from the Neolithic (6000-3500 BCE) to the Early Middle Ages (400-1000 CE).

Results: We found a high abundance of the archaeal genus Methanobrevibacter in the calculus. However, only a fraction of the sequences showed high similarity to Methanobrevibacter oralis, the only described Methanobrevibacter species in the human oral microbiome so far. To further investigate the diversity of this genus, we used de novo metagenome assembly to reconstruct 11 Methanobrevibacter genomes from the ancient calculus samples. Besides the presence of M. oralis in one of the samples, our phylogenetic analysis revealed two hitherto uncharacterised and unnamed oral Methanobrevibacter species that are prevalent in ancient calculus samples sampled from a broad range of geographical locations and time periods.

Conclusions: We have shown the potential of using de novo metagenomic assembly on ancient samples to explore microbial diversity and evolution. Our study suggests that there has been a possible shift in the human oral microbiome member Methanobrevibacter over the last millennia. Video abstract.
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http://dx.doi.org/10.1186/s40168-021-01132-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485483PMC
September 2021

DNA methylation profiling in mummified human remains from the eighteenth-century.

Sci Rep 2021 07 29;11(1):15493. Epub 2021 Jul 29.

Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Pauwelsstrasse 20, 52074, Aachen, Germany.

Reconstruction of ancient epigenomes by DNA methylation (DNAm) can shed light into the composition of cell types, disease states, and age at death. However, such analysis is hampered by impaired DNA quality and little is known how decomposition affects DNAm. In this study, we determined if EPIC Illumina BeadChip technology is applicable for specimens from mummies of the eighteenth century CE. Overall, the signal intensity on the microarray was extremely low, but for one of two samples we were able to detect characteristic DNAm signals in a subset of CG dinucleotides (CpGs), which were selected with a stringent processing pipeline. Using only these CpGs we could train epigenetic signatures with reference DNAm profiles of multiple tissues and our predictions matched the fact that the specimen was lung tissue from a 28-year-old woman. Thus, we provide proof of principle that Illumina BeadChips are applicable for DNAm profiling in ancient samples.
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http://dx.doi.org/10.1038/s41598-021-95021-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322318PMC
July 2021

The elusive parasite: comparing macroscopic, immunological, and genomic approaches to identifying malaria in human skeletal remains from Sayala, Egypt (third to sixth centuries AD).

Archaeol Anthropol Sci 2021 14;13(7):115. Epub 2021 Jun 14.

Bioarchaeology Department, Austrian Archaeological Institute at the Austrian Academy of Sciences, Franz Klein-Gasse 1, 1190 Vienna, Austria.

Although malaria is one of the oldest and most widely distributed diseases affecting humans, identifying and characterizing its presence in ancient human remains continue to challenge researchers. We attempted to establish a reliable approach to detecting malaria in human skeletons using multiple avenues of analysis: macroscopic observations, rapid diagnostic tests, and shotgun-capture sequencing techniques, to identify pathological changes, antigens, and DNA, respectively. Bone and tooth samples from ten individuals who displayed skeletal lesions associated with anaemia, from a site in southern Egypt (third to sixth centuries AD), were selected. antigens were detected in five of the ten bone samples, and traces of aDNA were detected in six of the twenty bone and tooth samples. There was relatively good synchronicity between the biomolecular findings, despite not being able to authenticate the results. This study highlights the complexity and limitations in the conclusive identification of the parasite in ancient human skeletons. Limitations regarding antigen and aDNA preservation and the importance of sample selection are at the forefront of the search for malaria in the past. We confirm that, currently, palaeopathological changes such as cribra are not enough to be certain of the presence of malaria. While biomolecular methods are likely the best chance for conclusive identification, we were unable to obtain results which correspond to the current authentication criteria of biomolecules. This study represents an important contribution in the refinement of biomolecular techniques used; also, it raises new insight regarding the consistency of combining several approaches in the identification of malaria in past populations.

Supplementary Information: The online version contains supplementary material available at 10.1007/s12520-021-01350-z.
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http://dx.doi.org/10.1007/s12520-021-01350-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202054PMC
June 2021

Reconstruction of ancient microbial genomes from the human gut.

Nature 2021 06 12;594(7862):234-239. Epub 2021 May 12.

Section on Pathophysiology and Molecular Pharmacology, Joslin Diabetes Center, Boston, MA, USA.

Loss of gut microbial diversity in industrial populations is associated with chronic diseases, underscoring the importance of studying our ancestral gut microbiome. However, relatively little is known about the composition of pre-industrial gut microbiomes. Here we performed a large-scale de novo assembly of microbial genomes from palaeofaeces. From eight authenticated human palaeofaeces samples (1,000-2,000 years old) with well-preserved DNA from southwestern USA and Mexico, we reconstructed 498 medium- and high-quality microbial genomes. Among the 181 genomes with the strongest evidence of being ancient and of human gut origin, 39% represent previously undescribed species-level genome bins. Tip dating suggests an approximate diversification timeline for the key human symbiont Methanobrevibacter smithii. In comparison to 789 present-day human gut microbiome samples from eight countries, the palaeofaeces samples are more similar to non-industrialized than industrialized human gut microbiomes. Functional profiling of the palaeofaeces samples reveals a markedly lower abundance of antibiotic-resistance and mucin-degrading genes, as well as enrichment of mobile genetic elements relative to industrial gut microbiomes. This study facilitates the discovery and characterization of previously undescribed gut microorganisms from ancient microbiomes and the investigation of the evolutionary history of the human gut microbiota through genome reconstruction from palaeofaeces.
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http://dx.doi.org/10.1038/s41586-021-03532-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189908PMC
June 2021

Ancient DNA analysis of rare genetic bone disorders.

Int J Paleopathol 2021 06 7;33:182-187. Epub 2021 May 7.

Institute for Mummy Studies, Eurac Research, Bolzano, Italy.

Objective: Review of the current advancements in the field of paleogenetics that provide new opportunities in studying the evolution of rare genetic bone diseases.

Material And Methods: Based on cases from the literature, the genetics of rare bone diseases will be introduced and the main methodological issues will be addressed, focusing on the opportunities presented by the application of aDNA analyses in the field of paleopathology.

Results: Medical literature provides large datasets on the genes responsible for rare bone disorders. These genes, subdivided in functional categories, display important future targets when analyzing rare genetic bone disorders in ancient human remains.

Conclusions: Knowledge on both phenotype and genotype is required to study rare diseases in ancient human remains.

Significance: The proposed interdisciplinary research will provide new insight into the occurrence and spread of genetic risk factors in the past and will help in the diagnostics of these rare and often neglected diseases.

Limitations: The current limitations in ancient DNA research and targeting the disease-causing specific mutations (e.g., somatic or germline).

Suggestions For Further Research: Methodological advancements and candidate gene lists provide the optimal basis for future interdisciplinary studies of rare genetic bone disorders in ancient human remains.
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http://dx.doi.org/10.1016/j.ijpp.2021.04.009DOI Listing
June 2021

Verification of tuberculosis infection among Vác mummies (18th century CE, Hungary) based on lipid biomarker profiling with a new HPLC-HESI-MS approach.

Tuberculosis (Edinb) 2021 01 8;126:102037. Epub 2020 Dec 8.

Department of Biological Anthropology, Faculty of Science and Informatics, University of Szeged, Hungary. Postal address: Közép fasor 52, H-6726, Szeged, Hungary. Electronic address:

Tuberculosis (TB) was a large burden of infections that peaked during the 19th century in Europe. Mummies from the 18th century CE, discovered in the crypt of a church at Vác, Hungary, had high TB prevalence, as revealed by amplification of key fragments of TB DNA and genome-wide TB analysis. Complementary methods are needed to confirm these diagnoses and one approach uses the identification of specific lipid biomarkers, such as TB mycocerosic acids (MCs). Previously, MC derivatives were profiled by specialised gas chromatography-mass spectrometry (GC-MS), so an alternative more direct approach has been developed. Underivatized MCs are extracted and analysed by high-performance liquid chromatography linked to a mass spectrometer, in heated electrospray ionisation mode (HPLC-HESI-MS). The method was validated using representatives of the Mycobacterium tuberculosis complex and other mycobacteria and tested on six Vác mummy cases, previously considered positive for TB infection. Analysing both rib and soft tissue samples, four out of six cases gave profiles of main C32 and major C29 and C39 mycocerosates correlating well with those of M. tuberculosis. Multidisciplinary methods are needed in the diagnosis of ancient tuberculosis; this new protocol accesses important confirmatory evidence, as demonstrated by the confirmation of TB in the Vác mummies.
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http://dx.doi.org/10.1016/j.tube.2020.102037DOI Listing
January 2021

Analysis of 1321 Eubacterium rectale genomes from metagenomes uncovers complex phylogeographic population structure and subspecies functional adaptations.

Genome Biol 2020 06 8;21(1):138. Epub 2020 Jun 8.

Department CIBIO, University of Trento, Trento, Italy.

Background: Eubacterium rectale is one of the most prevalent human gut bacteria, but its diversity and population genetics are not well understood because large-scale whole-genome investigations of this microbe have not been carried out.

Results: Here, we leverage metagenomic assembly followed by a reference-based binning strategy to screen over 6500 gut metagenomes spanning geography and lifestyle and reconstruct over 1300 E. rectale high-quality genomes from metagenomes. We extend previous results of biogeographic stratification, identifying a new subspecies predominantly found in African individuals and showing that closely related non-human primates do not harbor E. rectale. Comparison of pairwise genetic and geographic distances between subspecies suggests that isolation by distance and co-dispersal with human populations might have contributed to shaping the contemporary population structure of E. rectale. We confirm that a relatively recently diverged E. rectale subspecies specific to Europe consistently lacks motility operons and that it is immotile in vitro, probably due to ancestral genetic loss. The same subspecies exhibits expansion of its carbohydrate metabolism gene repertoire including the acquisition of a genomic island strongly enriched in glycosyltransferase genes involved in exopolysaccharide synthesis.

Conclusions: Our study provides new insights into the population structure and ecology of E. rectale and shows that shotgun metagenomes can enable population genomics studies of microbiota members at a resolution and scale previously attainable only by extensive isolate sequencing.
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http://dx.doi.org/10.1186/s13059-020-02042-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278147PMC
June 2020

in ancient human remains.

World J Gastroenterol 2019 Nov;25(42):6289-6298

Institute for Mummy Studies, EURAC Research, Bolzano 39100, Italy.

The bacterium () infects the stomachs of approximately 50% of all humans. With its universal occurrence, high infectivity and virulence properties it is considered as one of the most severe global burdens of modern humankind. It has accompanied humans for many thousands of years, and due to its high genetic variability and vertical transmission, its population genetics reflects the history of human migrations. However, especially complex demographic events such as the colonisation of Europe cannot be resolved with population genetic analysis of modern strains alone. This is best exemplified with the reconstruction of the 5300-year-old genome of the Iceman, a European Copper Age mummy. Our analysis provided precious insights into the ancestry and evolution of the pathogen and underlined the high complexity of ancient European population history. In this review we will provide an overview on the molecular analysis of in mummified human remains that were done so far and we will outline methodological advancements in the field of ancient DNA research that support the reconstruction and authentication of ancient genome sequences.
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http://dx.doi.org/10.3748/wjg.v25.i42.6289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861846PMC
November 2019

Molecular Reconstruction of the Diet in Human Stool Samples.

Authors:
Frank Maixner

mSystems 2019 Nov 5;4(6). Epub 2019 Nov 5.

Eurac Research - Institute for Mummy Studies, Bolzano, Italy

Understanding dietary effects on the gut microbial composition is one of the key questions in human microbiome research. It is highly important to have reliable dietary data on the stool samples to unambiguously link the microbiome composition to food intake. Often, however, self-reported diet surveys have low accuracy and can be misleading. Thereby, additional molecular biology-based methods could help to revise the diet composition. The article by Reese et al. [A. T. Reese, T. R. Kartzinel, B. L. Petrone, P. J. Turnbaugh, et al., mSystems 4(5):e00458-19, 2019, https://doi.org/10.1128/mSystems.00458-19] in a recent issue of describes a DNA metabarcoding strategy targeting chloroplast DNA markers in stool samples from 11 human subjects consuming both controlled and freely selected diets. The aim of this study was to evaluate the efficiency of this molecular method in detecting plant remains in the sample compared to the written dietary records. This study displays an important first step in implementing molecular dietary reconstructions in stool microbiome studies which will finally help to increase the accuracy of dietary metadata.
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http://dx.doi.org/10.1128/mSystems.00634-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6832023PMC
November 2019

The Prevotella copri Complex Comprises Four Distinct Clades Underrepresented in Westernized Populations.

Cell Host Microbe 2019 11 10;26(5):666-679.e7. Epub 2019 Oct 10.

CIBIO Department, University of Trento, 38123 Trento, Italy. Electronic address:

Prevotella copri is a common human gut microbe that has been both positively and negatively associated with host health. In a cross-continent meta-analysis exploiting >6,500 metagenomes, we obtained >1,000 genomes and explored the genetic and population structure of P. copri. P. copri encompasses four distinct clades (>10% inter-clade genetic divergence) that we propose constitute the P. copri complex, and all clades were confirmed by isolate sequencing. These clades are nearly ubiquitous and co-present in non-Westernized populations. Genomic analysis showed substantial functional diversity in the complex with notable differences in carbohydrate metabolism, suggesting that multi-generational dietary modifications may be driving reduced prevalence in Westernized populations. Analysis of ancient metagenomes highlighted patterns of P. copri presence consistent with modern non-Westernized populations and a clade delineation time pre-dating human migratory waves out of Africa. These findings reveal that P. copri exhibits a high diversity that is underrepresented in Western-lifestyle populations.
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http://dx.doi.org/10.1016/j.chom.2019.08.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854460PMC
November 2019

The Current Situation of the Tyrolean Iceman.

Gerontology 2019 10;65(6):699-706. Epub 2019 Sep 10.

Institute for Mummy Studies, Eurac Research, Bolzano, Italy.

The Tyrolean Iceman, commonly known as Ötzi, is the world's oldest glacier mummy and one of the best investigated ancient human remains in the world. Since the discovery of the 5,300-year-old Copper Age individual in 1991, in a glacier in the Eastern Italian Alps, a variety of morphological, biochemical, and molecular analyses have been performed that revealed important insights into his origin, his life habits, and the circumstances surrounding his demise. In more recent research, the mummy was subjected to cutting-edge modern research methodologies currently focusing on high-throughput sequence analysis of ancient biomolecules (DNA, proteins, lipids) that are still preserved in the mummified tissues. This application of innovative "-omics" technologies revealed novel insights on the ancestry, disease predisposition, diet, and the presence of pathogens in the glacier mummy. In this review, the most important and actual results of the molecular studies will be highlighted.
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http://dx.doi.org/10.1159/000501878DOI Listing
April 2020

Ancient genome-wide analyses infer kinship structure in an Early Medieval Alemannic graveyard.

Sci Adv 2018 09 5;4(9):eaao1262. Epub 2018 Sep 5.

Institute for Mummy Studies, EURAC Research, Viale Druso 1, 39100 Bolzano, Italy.

From historical and archeological records, it is posited that the European medieval household was a combination of close relatives and recruits. However, this kinship structure has not yet been directly tested at a genomic level on medieval burials. The early 7th century CE burial at Niederstotzingen, discovered in 1962, is the most complete and richest example of Alemannic funerary practice in Germany. Excavations found 13 individuals who were buried with an array of inscribed bridle gear, jewelry, armor, and swords. These artifacts support the view that the individuals had contact with France, northern Italy, and Byzantium. This study analyzed genome-wide sequences recovered from the remains, in tandem with analysis of the archeological context, to reconstruct kinship and the extent of outside contact. Eleven individuals had sufficient DNA preservation to genetically sex them as male and identify nine unique mitochondrial haplotypes and two distinct Y chromosome lineages. Genome-wide analyses were performed on eight individuals to estimate genetic affiliation to modern west Eurasians and genetic kinship at the burial. Five individuals were direct relatives. Three other individuals were not detectably related; two of these showed genomic affinity to southern Europeans. The genetic makeup of the individuals shares no observable pattern with their orientation in the burial or the cultural association of their grave goods, with the five related individuals buried with grave goods associated with three diverse cultural origins. These findings support the idea that not only were kinship and fellowship held in equal regard: Diverse cultural appropriation was practiced among closely related individuals as well.
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http://dx.doi.org/10.1126/sciadv.aao1262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6124919PMC
September 2018

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

The Sommersdorf mummies-An interdisciplinary investigation on human remains from a 17th-19th century aristocratic crypt in southern Germany.

PLoS One 2017 31;12(8):e0183588. Epub 2017 Aug 31.

Department of Physical Anthropology, Institute of Forensic Medicine, University of Bern, Bern, Switzerland.

Sommersdorf Castle (Bavaria, Germany) is a medieval castle complex which has been inhabited by the aristocratic family von Crailsheim. The deceased were entombed in a crypt located in the parapets underneath the castle's church, resulting in mummification of the bodies. Based on the family chronicle and oral history, identities have been ascribed to the mummies. The aim of the study is therefore to test the accuracy of the historical records in comparison to archaeological, anthropological and genetic data. Today, the crypt houses eleven wooden coffins from the 17th to 19th century AD. In ten of these, mummified and scattered human remains were found. Archive records were studied in order to identify names, ancestry, titles, occupation, date of birth and death, and place of interment of the individuals. The coffins were visually inspected and dated by typo-chronology, and the mummified and scattered skeletal remains were subjected to a physical anthropological examination. In total, the crypt contains the remains of a minimum number of nine individuals, among them three adult males, five adult females and one infant. A detailed scientific examination, including prior conservation, ancient DNA analyses, and computed tomography (CT), was performed on five mummies. By means of the CT data age at death, sex, body height, pathologies, and anatomical variants were investigated. CT analysis further showed that the bodies were naturally mummified. Mitochondrial DNA analyses revealed that the tested individuals are not maternally related. In addition, health, living conditions and circumstances of death of the entombed individuals could be highlighted. Being confronted with the strengths, weaknesses and limitations of each methodological approach, probable identification was achieved in two cases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183588PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578507PMC
October 2017

Deletion of the celA gene in Aspergillus nidulans triggers overexpression of secondary metabolite biosynthetic genes.

Sci Rep 2017 07 20;7(1):5978. Epub 2017 Jul 20.

University of Natural Resources and Life Sciences Vienna (BOKU), Department of Applied Genetics and Cell Biology, Fungal Genetics and Genomics Unit, BOKU Campus, Tulln/Donau, A-3430, Austria.

Although much progress has been made in the study of cell wall biosynthetic genes in the model filamentous fungus Aspergillus nidulans, there are still targets awaiting characterization. An example is the gene celA (ANIA_08444) encoding a putative mixed linkage glucan synthase. To characterize the role of celA, we deleted it in A. nidulans, analyzed the phenotype of the mycelium and performed RNA-Seq. The strain shows a very strong phenotype, namely "balloons" along the hyphae and aberrant conidiophores, as well as an altered susceptibility to cell wall drugs. These data suggest a potential role of the gene in cell wall-related processes. The Gene Ontology term Enrichment analysis shows increased expression of secondary metabolite biosynthetic genes (sterigmatocystin in particular) in the deleted strain. Our results show that the deletion of celA triggers a strong phenotype reminiscent of cell wall-related aberrations and the upregulation of some secondary metabolite gene clusters in A. nidulans.
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http://dx.doi.org/10.1038/s41598-017-05920-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519750PMC
July 2017

miRNAs in Ancient Tissue Specimens of the Tyrolean Iceman.

Mol Biol Evol 2017 04;34(4):793-801

Medical Faculty, Institute of Human Genetics, Saarland University, Homburg, Germany.

The analysis of nucleic acids in ancient samples is largely limited to DNA. Small noncoding RNAs (microRNAs) are known to be evolutionary conserved and stable. To gain knowledge on miRNAs measured from ancient samples, we profiled microRNAs in cryoconserved mummies. First, we established the approach on a World War One warrior, the "Kaiserjäger", which has been preserved for almost one century. Then, we profiled seven ancient tissue specimens including skeletal muscle, stomach mucosa, stomach content and two corpus organ tissues of the 5,300-year-old copper age mummy Iceman and compared these profiles to the presence of organ-specific miRNAs in modern tissues. Our analyses suggest the presence of specific miRNAs in the different Iceman's tissues. Of 1,066 analyzed human miRNAs, 31 were discovered across all biopsies and 87 miRNAs were detected only in a single sample. To check for potential microbiological contaminations, all miRNAs detected in Iceman samples and not present in ancient samples were mapped to 14,582 bacterial and viral genomes. We detected few hits (3.9% of miRNAs compared with 3.6% of miRNAs). Interestingly, the miRNAs with higher abundance across all ancient tissues were significantly enriched for Guanine (P value of 10-13) and Cytosine (P value of 10-7). The same pattern was observed for modern tissues. Comparing miRNAs measured from ancient organs to modern tissue patterns highlighted significant similarities, e.g., for miRNAs present in the muscle. Our first comprehensive analysis of microRNAs in ancient human tissues indicates that these stable molecules can be detected in tissue specimens after 5,300 years.
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http://dx.doi.org/10.1093/molbev/msw291DOI Listing
April 2017

Genetic structure of the early Hungarian conquerors inferred from mtDNA haplotypes and Y-chromosome haplogroups in a small cemetery.

Mol Genet Genomics 2017 Feb 1;292(1):201-214. Epub 2016 Nov 1.

Department of Genetics, University of Szeged, Szeged, Hungary.

We applied ancient DNA methods to shed light on the origin of ancient Hungarians and their relation to modern populations. Hungarians moved into the Carpathian Basin from the Eurasian Pontic steppes in the year 895 AD as a confederation of seven tribes, but their further origin remains obscure. Here, we present 17 mtDNA haplotypes and four Y-chromosome haplogroups, which portray the genetic composition of an entire small cemetery of the first generation Hungarians. Using novel algorithms to compare these mitochondrial DNA haplogroups with other ancient and modern Eurasian data, we revealed that a significant portion of the Hungarians probably originated from a long ago consolidated gene pool in Central Asia-South Siberia, which still persists in modern Hungarians. Another genetic layer of the early Hungarians was obtained during their westward migrations by admixing with various populations of European origin, and an important component of these was derived from the Caucasus region. Most of the modern populations, which are genetically closest relatives of ancient Hungarians, today speak non-Indo-European languages. Our results contribute to our understanding of the peopling of Europe by providing ancient DNA data from a still genetically poorly studied period of medieval human migrations.
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http://dx.doi.org/10.1007/s00438-016-1267-zDOI Listing
February 2017

A whole mitochondria analysis of the Tyrolean Iceman's leather provides insights into the animal sources of Copper Age clothing.

Sci Rep 2016 08 18;6:31279. Epub 2016 Aug 18.

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

The attire of the Tyrolean Iceman, a 5,300-year-old natural mummy from the Ötzal Italian Alps, provides a surviving example of ancient manufacturing technologies. Research into his garments has however, been limited by ambiguity surrounding their source species. Here we present a targeted enrichment and sequencing of full mitochondrial genomes sampled from his clothes and quiver, which elucidates the species of production for nine fragments. Results indicate that the majority of the samples originate from domestic ungulate species (cattle, sheep and goat), whose recovered haplogroups are now at high frequency in today's domestic populations. Intriguingly, the hat and quiver samples were produced from wild species, brown bear and roe deer respectively. Combined, these results suggest that Copper Age populations made considered choices of clothing material from both the wild and domestic populations available to them. Moreover, these results show the potential for the recovery of complete mitochondrial genomes from degraded prehistoric artefacts.
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http://dx.doi.org/10.1038/srep31279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4989873PMC
August 2016

Tuberculosis in early medieval Switzerland--osteological and molecular evidence.

Swiss Med Wkly 2016 31;146:w14269. Epub 2016 Jan 31.

Department of Physical Anthropology, Institute of Forensic Medicine, Bern University, Switzerland.

Lesions consistent with skeletal tuberculosis were found in 13 individuals from an early medieval skeletal sample from Courroux (Switzerland). One case of Pott's disease as well as lytic lesions in vertebrae and joints, rib lesions and endocranial new bone formation were identified. Three individuals with lesions and one without were tested for the presence of Myobacterium tuberculosis complex (MTBC) ancient DNA (aDNA), and in two cases, evidence for MTBC aDNA was detected. Our results suggest the presence of tuberculosis in the analysed material, which is in accordance with other osteological and biomolecular research that reported a high prevalence of tuberculosis in medieval skeletons.
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http://dx.doi.org/10.4414/smw.2016.14269DOI Listing
October 2016

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

Tuberculosis in Late Neolithic-Early Copper Age human skeletal remains from Hungary.

Tuberculosis (Edinb) 2015 Jun 13;95 Suppl 1:S18-22. Epub 2015 Feb 13.

Institute for Mummies and the Iceman, EURAC Research, Bolzano, Italy.

Alsónyék-Bátaszék in Southern Hungary is one of the largest late Neolithic settlements and cemeteries excavated in Central Europe. In total, 2359 burials from the Late Neolithic - Early Copper Age Lengyel culture were found between 2006 and 2009 [1]. Anthropological investigations previously carried out on individuals from this site revealed an interesting paleopathological case of tuberculosis in the form of Pott's disease dated to the early 5(th) millennium BC. In this study, selected specimens from this osteoarcheological series were subjected to paleomicrobiological analysis to establish the presence of MTBC bacteria. As all individuals showing clear osteological signs of TB infection belonged to a single grave group, 38 individuals from this grave group were analysed. The sample included the case of Pott's disease as well as individuals both with and without osseous TB manifestations. The detection of TB DNA in the individual with Pott's disease provided further evidence for the occurrence of TB in Neolithic populations of Europe. Moreover, our molecular analysis indicated that several other individuals of the same grave group were also infected with TB, opening the possibility for further analyses of this unique Neolithic skeletal series.
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http://dx.doi.org/10.1016/j.tube.2015.02.011DOI Listing
June 2015

Human tuberculosis predates domestication in ancient Syria.

Tuberculosis (Edinb) 2015 Jun 26;95 Suppl 1:S4-S12. Epub 2015 Feb 26.

Laboratoire d'Anthropologie biologique Paul Broca, Ecole Pratique des Hautes Etudes, Paris, France; De la Préhistoire à l'Actuel: Culture, Environnement, Anthropologie (PACEA, UMR 5199, CNRS, Université de Bordeaux, Ministère de la Culture et de la Communication), Allée Geoffroy St Hilaire, CS 50023, 33615 Pessac Cedex, France; Department of Anthropology, University of Western Ontario, London, Canada. Electronic address:

The question of pre-neolithic tuberculosis is still open in paleopathological perspective. One of the major interests is to explore what type of infection could have existed around the early stage of animal domestication. Paleopathological lesions evoking skeletal TB were observed on five human skeletons coming from two PPNB sites in Syria, which belongs to the geographical cradle of agriculture. These sites represent respectively pre-domestication phase (Dja'de el Mughara, Northern Syria, 8800-8300 BCE cal.) and early domestication phase (Tell Aswad, Southern Syria, 8200-7600 BCE cal.). MicroCT scan analyses were performed on two specimens (one per site) and revealed microscopic changes in favor of TB infection. Detection of lipid biomarkers is positive for two specimens (one per site). Initial molecular analysis further indicates the presence of TB in one individual from Dja'de. Interestingly, no morphological evidence of TB was observed on animal remains of wild and newly domesticated species, discovered in these sites. These observations strongly suggest the presence of human tuberculosis before domestication and at its early stages.
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http://dx.doi.org/10.1016/j.tube.2015.02.001DOI Listing
June 2015

Tuberculosis infection in a late-medieval Hungarian population.

Tuberculosis (Edinb) 2015 Jun 13;95 Suppl 1:S60-4. Epub 2015 Feb 13.

Department of Biological Anthropology, University of Szeged, Szeged, Hungary.

The AD 16-17(th) century skeletal series from Bácsalmás-Óalmás (southern Hungary) has already been the subject of previous paleopathological studies concerning TB-related bone lesions. Due to recent development of macroscopic and molecular diagnostic methods in paleopathology and paleomicrobiology, a five-year international research program was recently started in order to re-evaluate the TB-related lesions in the complete series, comprising 481 skeletons. The skeletal material of these individuals was examined using macromorphological methods focusing on both classical/advanced stage skeletal TB alterations and atypical/early-stage TB lesions. Paleomicrobial analysis was used to study the presence of Mycobacterium tuberculosis complex (MTBC) DNA both in morphologically positive and negative cases. Samples were tested for the repetitive element IS6110 and further characterized by spoligotyping. In the whole series, 283 possible cases of TB infections were identified based on morphological alterations. Skeletal samples of eighteen individuals, morphologically positive as well as negative cases, were selected for further biomolecular examinations. Among them, seven individuals were PCR positive for the repetitive IS6110 sequence of the MTBC genome. Compared to the few cases of TB from the Bácsalmás-Óalmás series previously described, a much higher prevalence of MTBC infected skeletons was revealed in this study. The atypical/early stage skeletal lesions occurred significantly more frequently than the so-called classical alterations. Paleomicrobial analysis confirmed a prevalence of MTBC infection nearing 40% among the selected sample. Preliminary results also indicated better preservation of bacterial DNA in the compact layer of long bones and teeth, while spoligotyping suggested infection by different MTBC pathogens.
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http://dx.doi.org/10.1016/j.tube.2015.02.010DOI Listing
June 2015

Evidence for tuberculosis in 18th/19th century slaves in Anse Sainte-Marguerite (Guadeloupe - French Western Indies).

Tuberculosis (Edinb) 2015 Jun 12;95 Suppl 1:S65-8. Epub 2015 Feb 12.

Institute for Mummies and the Iceman, EURAC, Bolzano, Italy.

During the American colonization in the 18th and 19th century, Africans were captured and shipped to America. Harsh living and working conditions often led to chronic diseases and high mortality rates. Slaves in the Caribbean were forced to work mainly on sugar plantations. They were buried in cemeteries like Anse Sainte-Marguerite on the isle of Grande-Terre (Guadeloupe) which was examined by archaeologists and physical anthropologists. Morphological studies on osseous remains of 148 individuals revealed 15 cases with signs for bone tuberculosis and a high frequency of periosteal reactions which indicates early stages of the disease. 11 bone samples from these cemeteries were analysed for ancient DNA. The samples were extracted with established procedures and examined for the cytoplasmic multicopy β-actin gene and Mycobacterium tuberculosis complex DNA (IS 6110) by PCR. An amplification product for M. tuberculosis with the size of 123 bp was obtained. Sequencing confirmed the result. This study shows evidence of M. tuberculosis complex DNA in a Caribbean slave population.
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http://dx.doi.org/10.1016/j.tube.2015.02.006DOI Listing
June 2015

Genomic correlates of atherosclerosis in ancient humans.

Glob Heart 2014 Jun;9(2):203-9

Institute of Archaeological Sciences, University of Tubingen, Tubingen, Germany.

Paleogenetics offers a unique opportunity to study human evolution, population dynamics, and disease evolution in situ. Although histologic and computed x-ray tomographic investigations of ancient mummies have clearly shown that atherosclerosis has been present in humans for more than 5,000 years, limited data are available on the presence of genetic predisposition for cardiovascular disease in ancient human populations. In a previous whole-genome study of the Tyrolean Iceman, a 5,300-year-old glacier mummy from the Alps, an increased risk for coronary heart disease was detected. The Iceman's genome revealed several single nucleotide polymorphisms that are linked with cardiovascular disease in genome-wide association studies. Future genetic studies of ancient humans from various geographic origins and time periods have the potential to provide more insights into the presence and possible changes of genetic risk factors in our ancestors. The study of ancient humans and a better understanding of the interaction between environmental and genetic influences on the development of heart diseases may lead to a more effective prevention and treatment of the most common cause of death in the modern world.
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http://dx.doi.org/10.1016/j.gheart.2014.03.2453DOI Listing
June 2014

Metagenomic analysis reveals presence of Treponema denticola in a tissue biopsy of the Iceman.

PLoS One 2014 18;9(6):e99994. Epub 2014 Jun 18.

CUBE - Division of Computational Systems Biology, Department of Microbiology and Ecosystem Science, University of Vienna, Vienna, Austria.

Ancient hominoid genome studies can be regarded by definition as metagenomic analyses since they represent a mixture of both hominoid and microbial sequences in an environment. Here, we report the molecular detection of the oral spirochete Treponema denticola in ancient human tissue biopsies of the Iceman, a 5,300-year-old Copper Age natural ice mummy. Initially, the metagenomic data of the Iceman's genomic survey was screened for bacterial ribosomal RNA (rRNA) specific reads. Through ranking the reads by abundance a relatively high number of rRNA reads most similar to T. denticola was detected. Mapping of the metagenome sequences against the T. denticola genome revealed additional reads most similar to this opportunistic pathogen. The DNA damage pattern of specifically mapped reads suggests an ancient origin of these sequences. The haematogenous spread of bacteria of the oral microbiome often reported in the recent literature could already explain the presence of metagenomic reads specific for T. denticola in the Iceman's bone biopsy. We extended, however, our survey to an Iceman gingival tissue sample and a mouth swab sample and could thereby detect T. denticola and Porphyrimonas gingivalis, another important member of the human commensal oral microflora. Taken together, this study clearly underlines the opportunity to detect disease-associated microorganisms when applying metagenomics-enabled approaches on datasets of ancient human remains.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0099994PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4062476PMC
July 2015

Population genomic analysis of ancient and modern genomes yields new insights into the genetic ancestry of the Tyrolean Iceman and the genetic structure of Europe.

PLoS Genet 2014 May 8;10(5):e1004353. Epub 2014 May 8.

Department of Genetics, Stanford University, Stanford, California, United States of America.

Genome sequencing of the 5,300-year-old mummy of the Tyrolean Iceman, found in 1991 on a glacier near the border of Italy and Austria, has yielded new insights into his origin and relationship to modern European populations. A key finding of that study was an apparent recent common ancestry with individuals from Sardinia, based largely on the Y chromosome haplogroup and common autosomal SNP variation. Here, we compiled and analyzed genomic datasets from both modern and ancient Europeans, including genome sequence data from over 400 Sardinians and two ancient Thracians from Bulgaria, to investigate this result in greater detail and determine its implications for the genetic structure of Neolithic Europe. Using whole-genome sequencing data, we confirm that the Iceman is, indeed, most closely related to Sardinians. Furthermore, we show that this relationship extends to other individuals from cultural contexts associated with the spread of agriculture during the Neolithic transition, in contrast to individuals from a hunter-gatherer context. We hypothesize that this genetic affinity of ancient samples from different parts of Europe with Sardinians represents a common genetic component that was geographically widespread across Europe during the Neolithic, likely related to migrations and population expansions associated with the spread of agriculture.
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http://dx.doi.org/10.1371/journal.pgen.1004353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4014435PMC
May 2014

Demographic histories, isolation and social factors as determinants of the genetic structure of Alpine linguistic groups.

PLoS One 2013 2;8(12):e81704. Epub 2013 Dec 2.

Accademia Europea di Bolzano (EURAC), Istituto per le Mummie e l'Iceman, Bolzano, Italy.

Great European mountain ranges have acted as barriers to gene flow for resident populations since prehistory and have offered a place for the settlement of small, and sometimes culturally diverse, communities. Therefore, the human groups that have settled in these areas are worth exploring as an important potential source of diversity in the genetic structure of European populations. In this study, we present new high resolution data concerning Y chromosomal variation in three distinct Alpine ethno-linguistic groups, Italian, Ladin and German. Combining unpublished and literature data on Y chromosome and mitochondrial variation, we were able to detect different genetic patterns. In fact, within and among population diversity values observed vary across linguistic groups, with German and Italian speakers at the two extremes, and seem to reflect their different demographic histories. Using simulations we inferred that the joint effect of continued genetic isolation and reduced founding group size may explain the apportionment of genetic diversity observed in all groups. Extending the analysis to other continental populations, we observed that the genetic differentiation of Ladins and German speakers from Europeans is comparable or even greater to that observed for well known outliers like Sardinian and Basques. Finally, we found that in south Tyroleans, the social practice of Geschlossener Hof, a hereditary norm which might have favored male dispersal, coincides with a significant intra-group diversity for mtDNA but not for Y chromosome, a genetic pattern which is opposite to those expected among patrilocal populations. Together with previous evidence regarding the possible effects of "local ethnicity" on the genetic structure of German speakers that have settled in the eastern Italian Alps, this finding suggests that taking socio-cultural factors into account together with geographical variables and linguistic diversity may help unveil some yet to be understood aspects of the genetic structure of European populations.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0081704PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3847036PMC
September 2014
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