Publications by authors named "Ella Reiter"

15 Publications

  • Page 1 of 1

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

Geographically structured genomic diversity of non-human primate-infecting subsp. .

Microb Genom 2020 11;6(11)

Viral Evolution, Robert Koch Institute, Berlin, Germany.

Many non-human primate species in sub-Saharan Africa are infected with subsp. , the bacterium causing yaws in humans. In humans, yaws is often characterized by lesions of the extremities and face, while subsp. causes venereal syphilis and is typically characterized by primary lesions on the genital, anal or oral mucosae. It remains unclear whether other subspecies found in humans also occur in non-human primates and how the genomic diversity of non-human primate subsp. lineages is distributed across hosts and space. We observed orofacial and genital lesions in sooty mangabeys () in Taï National Park, Côte d'Ivoire and collected swabs and biopsies from symptomatic animals. We also collected non-human primate bones from 8 species in Taï National Park and 16 species from 11 other sites across sub-Saharan Africa. Samples were screened for DNA using polymerase chain reactions (PCRs) and we used in-solution hybridization capture to sequence genomes. We generated three nearly complete genomes from biopsies and swabs and detected treponemal DNA in bones of six non-human primate species in five countries, allowing us to reconstruct three partial genomes. Phylogenomic analyses revealed that both orofacial and genital lesions in sooty mangabeys from Taï National Park were caused by subsp. . We showed that subsp. has infected non-human primates in Taï National Park for at least 28 years and has been present in two non-human primate species that had not been described as subsp. hosts in this ecosystem, western chimpanzees () and western red colobus (), complementing clinical evidence that started accumulating in Taï National Park in 2014. More broadly, simian subsp. strains did not form monophyletic clades based on host species or the symptoms caused, but rather clustered based on geography. Geographical clustering of subsp. genomes might be compatible with cross-species transmission of subsp. within ecosystems or environmental exposure, leading to the acquisition of closely related strains. Finally, we found no evidence for mutations that confer antimicrobial resistance.
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http://dx.doi.org/10.1099/mgen.0.000463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725339PMC
November 2020

Author Correction: Ancient genomes reveal social and genetic structure of Late Neolithic Switzerland.

Nat Commun 2020 09 16;11(1):4759. Epub 2020 Sep 16.

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

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41467-020-18561-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494889PMC
September 2020

2000-year-old pathogen genomes reconstructed from metagenomic analysis of Egyptian mummified individuals.

BMC Biol 2020 08 28;18(1):108. Epub 2020 Aug 28.

Institute of Evolutionary Medicine, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.

Background: Recent advances in sequencing have facilitated large-scale analyses of the metagenomic composition of different samples, including the environmental microbiome of air, water, and soil, as well as the microbiome of living humans and other animals. Analyses of the microbiome of ancient human samples may provide insights into human health and disease, as well as pathogen evolution, but the field is still in its very early stages and considered highly challenging.

Results: The metagenomic and pathogen content of Egyptian mummified individuals from different time periods was investigated via genetic analysis of the microbial composition of various tissues. The analysis of the dental calculus' microbiome identified Red Complex bacteria, which are correlated with periodontal diseases. From bone and soft tissue, genomes of two ancient pathogens, a 2200-year-old Mycobacterium leprae strain and a 2000-year-old human hepatitis B virus, were successfully reconstructed.

Conclusions: The results show the reliability of metagenomic studies on Egyptian mummified individuals and the potential to use them as a source for the extraction of ancient pathogen DNA.
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http://dx.doi.org/10.1186/s12915-020-00839-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456089PMC
August 2020

Ancient genomes reveal social and genetic structure of Late Neolithic Switzerland.

Nat Commun 2020 04 20;11(1):1915. Epub 2020 Apr 20.

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

Genetic studies of Neolithic and Bronze Age skeletons from Europe have provided evidence for strong population genetic changes at the beginning and the end of the Neolithic period. To further understand the implications of these in Southern Central Europe, we analyze 96 ancient genomes from Switzerland, Southern Germany, and the Alsace region in France, covering the Middle/Late Neolithic to Early Bronze Age. Similar to previously described genetic changes in other parts of Europe from the early 3rd millennium BCE, we detect an arrival of ancestry related to Late Neolithic pastoralists from the Pontic-Caspian steppe in Switzerland as early as 2860-2460 calBCE. Our analyses suggest that this genetic turnover was a complex process lasting almost 1000 years and involved highly genetically structured populations in this region.
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http://dx.doi.org/10.1038/s41467-020-15560-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171184PMC
April 2020

Large-scale mitogenomic analysis of the phylogeography of the Late Pleistocene cave bear.

Sci Rep 2019 08 15;9(1):10700. Epub 2019 Aug 15.

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

The cave bear (Ursus spelaeus) is one of the Late Pleistocene megafauna species that faced extinction at the end of the last ice age. Although it is represented by one of the largest fossil records in Europe and has been subject to several interdisciplinary studies including palaeogenetic research, its fate remains highly controversial. Here, we used a combination of hybridisation capture and next generation sequencing to reconstruct 59 new complete cave bear mitochondrial genomes (mtDNA) from 14 sites in Western, Central and Eastern Europe. In a Bayesian phylogenetic analysis, we compared them to 64 published cave bear mtDNA sequences to reconstruct the population dynamics and phylogeography during the Late Pleistocene. We found five major mitochondrial DNA lineages resulting in a noticeably more complex biogeography of the European lineages during the last 50,000 years than previously assumed. Furthermore, our calculated effective female population sizes suggest a drastic cave bear population decline starting around 40,000 years ago at the onset of the Aurignacian, coinciding with the spread of anatomically modern humans in Europe. Thus, our study supports a potential significant human role in the general extinction and local extirpation of the European cave bear and illuminates the fate of this megafauna species.
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http://dx.doi.org/10.1038/s41598-019-47073-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6695494PMC
August 2019

Ratio of mitochondrial to nuclear DNA affects contamination estimates in ancient DNA analysis.

Sci Rep 2018 09 19;8(1):14075. Epub 2018 Sep 19.

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

In the last decade, ancient DNA research has grown rapidly and started to overcome several of its earlier limitations through Next-Generation-Sequencing (NGS). Among other advances, NGS allows direct estimation of sample contamination from modern DNA sources. First NGS-based approaches of estimating contamination measured heterozygosity. These measurements, however, could only be performed on haploid genomic regions, i.e. the mitochondrial genome or male X chromosomes, but provided no measures of contamination in the nuclear genome of females with their two X chromosomes. Instead, female nuclear contamination is routinely extrapolated from mitochondrial contamination estimates, but it remains unclear if this extrapolation is reliable and to what degree variation in mitochondrial to nuclear DNA ratios affects this extrapolation. We therefore analyzed ancient DNA from 317 samples of different skeletal elements from multiple sites, spanning a temporal range from 7,000 BP to 386 AD. We found that the mitochondrial to nuclear DNA (mt/nc) ratio negatively correlates with an increase in endogenous DNA content and strongly influenced mitochondrial and nuclear contamination estimates in males. The ratio of mt to nc contamination estimates remained stable for overall mt/nc ratios below 200, as found particularly often in petrous bones but less in other skeletal elements and became more variable above that ratio.
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http://dx.doi.org/10.1038/s41598-018-32083-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6145933PMC
September 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

The rate and potential relevance of new mutations in a colonizing plant lineage.

PLoS Genet 2018 02 12;14(2):e1007155. Epub 2018 Feb 12.

Department of Molecular Biology, Max Planck Institute for Developmental Biology, Tübingen, Germany.

By following the evolution of populations that are initially genetically homogeneous, much can be learned about core biological principles. For example, it allows for detailed studies of the rate of emergence of de novo mutations and their change in frequency due to drift and selection. Unfortunately, in multicellular organisms with generation times of months or years, it is difficult to set up and carry out such experiments over many generations. An alternative is provided by "natural evolution experiments" that started from colonizations or invasions of new habitats by selfing lineages. With limited or missing gene flow from other lineages, new mutations and their effects can be easily detected. North America has been colonized in historic times by the plant Arabidopsis thaliana, and although multiple intercrossing lineages are found today, many of the individuals belong to a single lineage, HPG1. To determine in this lineage the rate of substitutions-the subset of mutations that survived natural selection and drift-, we have sequenced genomes from plants collected between 1863 and 2006. We identified 73 modern and 27 herbarium specimens that belonged to HPG1. Using the estimated substitution rate, we infer that the last common HPG1 ancestor lived in the early 17th century, when it was most likely introduced by chance from Europe. Mutations in coding regions are depleted in frequency compared to those in other portions of the genome, consistent with purifying selection. Nevertheless, a handful of mutations is found at high frequency in present-day populations. We link these to detectable phenotypic variance in traits of known ecological importance, life history and growth, which could reflect their adaptive value. Our work showcases how, by applying genomics methods to a combination of modern and historic samples from colonizing lineages, we can directly study new mutations and their potential evolutionary relevance.
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http://dx.doi.org/10.1371/journal.pgen.1007155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5825158PMC
February 2018

Central European Woolly Mammoth Population Dynamics: Insights from Late Pleistocene Mitochondrial Genomes.

Sci Rep 2017 12 18;7(1):17714. Epub 2017 Dec 18.

Institute for Archaeological Science, University of Tübingen, Rümelinstraße 23, 72070, Tübingen, Germany.

The population dynamics of the Pleistocene woolly mammoth (Mammuthus primigenius) has been the subject of intensive palaeogenetic research. Although a large number of mitochondrial genomes across Eurasia have been reconstructed, the available data remains geographically sparse and mostly focused on eastern Eurasia. Thus, population dynamics in other regions have not been extensively investigated. Here, we use a multi-method approach utilising proteomic, stable isotope and genetic techniques to identify and generate twenty woolly mammoth mitochondrial genomes, and associated dietary stable isotopic data, from highly fragmentary Late Pleistocene material from central Europe. We begin to address region-specific questions regarding central European woolly mammoth populations, highlighting parallels with a previous replacement event in eastern Eurasia ten thousand years earlier. A high number of shared derived mutations between woolly mammoth mitochondrial clades are identified, questioning previous phylogenetic analysis and thus emphasizing the need for nuclear DNA studies to explicate the increasingly complex genetic history of the woolly mammoth.
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http://dx.doi.org/10.1038/s41598-017-17723-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735091PMC
December 2017

Reconstructing Asian faunal introductions to eastern Africa from multi-proxy biomolecular and archaeological datasets.

PLoS One 2017 17;12(8):e0182565. Epub 2017 Aug 17.

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

Human-mediated biological exchange has had global social and ecological impacts. In sub-Saharan Africa, several domestic and commensal animals were introduced from Asia in the pre-modern period; however, the timing and nature of these introductions remain contentious. One model supports introduction to the eastern African coast after the mid-first millennium CE, while another posits introduction dating back to 3000 BCE. These distinct scenarios have implications for understanding the emergence of long-distance maritime connectivity, and the ecological and economic impacts of introduced species. Resolution of this longstanding debate requires new efforts, given the lack of well-dated fauna from high-precision excavations, and ambiguous osteomorphological identifications. We analysed faunal remains from 22 eastern African sites spanning a wide geographic and chronological range, and applied biomolecular techniques to confirm identifications of two Asian taxa: domestic chicken (Gallus gallus) and black rat (Rattus rattus). Our approach included ancient DNA (aDNA) analysis aided by BLAST-based bioinformatics, Zooarchaeology by Mass Spectrometry (ZooMS) collagen fingerprinting, and direct AMS (accelerator mass spectrometry) radiocarbon dating. Our results support a late, mid-first millennium CE introduction of these species. We discuss the implications of our findings for models of biological exchange, and emphasize the applicability of our approach to tropical areas with poor bone preservation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0182565PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560628PMC
October 2017

Ancient Egyptian mummy genomes suggest an increase of Sub-Saharan African ancestry in post-Roman periods.

Nat Commun 2017 05 30;8:15694. Epub 2017 May 30.

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

Egypt, located on the isthmus of Africa, is an ideal region to study historical population dynamics due to its geographic location and documented interactions with ancient civilizations in Africa, Asia and Europe. Particularly, in the first millennium BCE Egypt endured foreign domination leading to growing numbers of foreigners living within its borders possibly contributing genetically to the local population. Here we present 90 mitochondrial genomes as well as genome-wide data sets from three individuals obtained from Egyptian mummies. The samples recovered from Middle Egypt span around 1,300 years of ancient Egyptian history from the New Kingdom to the Roman Period. Our analyses reveal that ancient Egyptians shared more ancestry with Near Easterners than present-day Egyptians, who received additional sub-Saharan admixture in more recent times. This analysis establishes ancient Egyptian mummies as a genetic source to study ancient human history and offers the perspective of deciphering Egypt's past at a genome-wide level.
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http://dx.doi.org/10.1038/ncomms15694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5459999PMC
May 2017

Extraction of ultrashort DNA molecules from herbarium specimens.

Biotechniques 2017 02 1;62(2):76-79. Epub 2017 Feb 1.

Research Group for Ancient Genomics and Evolution, Department of Molecular Biology, Max Planck Institute for Developmental Biology, Tübingen, Germany.

DNA extracted from herbarium specimens is highly fragmented; therefore, it is crucial to use extraction protocols that retrieve short DNA molecules. Improvements in extraction and DNA library preparation protocols for animal remains have allowed efficient retrieval of molecules shorter than 50 bp. Here, we applied these improvements to DNA extraction protocols for herbarium specimens and evaluated extraction performance by shotgun sequencing, which allows an accurate estimation of the distribution of DNA fragment lengths. Extraction with N-phenacylthiazolium bromide (PTB) buffer decreased median fragment length by 35% when compared with cetyl-trimethyl ammonium bromide (CTAB); modifying the binding conditions of DNA to silica allowed for an additional decrease of 10%. We did not observe a further decrease in length for single-stranded DNA (ssDNA) versus double-stranded DNA (dsDNA) library preparation methods. Our protocol enables the retrieval of ultrashort molecules from herbarium specimens, which will help to unlock the genetic information stored in herbaria.
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http://dx.doi.org/10.2144/000114517DOI Listing
February 2017

Temporal patterns of damage and decay kinetics of DNA retrieved from plant herbarium specimens.

R Soc Open Sci 2016 Jun 22;3(6):160239. Epub 2016 Jun 22.

Research Group for Ancient Genomics and Evolution, Department of Molecular Biology , Max Planck Institute for Developmental Biology , Tuebingen 72076 , Germany.

Herbaria archive a record of changes of worldwide plant biodiversity harbouring millions of specimens that contain DNA suitable for genome sequencing. To profit from this resource, it is fundamental to understand in detail the process of DNA degradation in herbarium specimens. We investigated patterns of DNA fragmentation and nucleotide misincorporation by analysing 86 herbarium samples spanning the last 300 years using Illumina shotgun sequencing. We found an exponential decay relationship between DNA fragmentation and time, and estimated a per nucleotide fragmentation rate of 1.66 × 10(-4) per year, which is six times faster than the rate estimated for ancient bones. Additionally, we found that strand breaks occur specially before purines, and that depurination-driven DNA breakage occurs constantly through time and can to a great extent explain decreasing fragment length over time. Similar to what has been found analysing ancient DNA from bones, we found a strong correlation between the deamination-driven accumulation of cytosine to thymine substitutions and time, which reinforces the importance of substitution patterns to authenticate the ancient/historical nature of DNA fragments. Accurate estimations of DNA degradation through time will allow informed decisions about laboratory and computational procedures to take advantage of the vast collection of worldwide herbarium specimens.
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http://dx.doi.org/10.1098/rsos.160239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929915PMC
June 2016

Genomic analysis of 6,000-year-old cultivated grain illuminates the domestication history of barley.

Nat Genet 2016 09 18;48(9):1089-93. Epub 2016 Jul 18.

Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) Gatersleben, Seeland, Germany.

The cereal grass barley was domesticated about 10,000 years before the present in the Fertile Crescent and became a founder crop of Neolithic agriculture. Here we report the genome sequences of five 6,000-year-old barley grains excavated at a cave in the Judean Desert close to the Dead Sea. Comparison to whole-exome sequence data from a diversity panel of present-day barley accessions showed the close affinity of ancient samples to extant landraces from the Southern Levant and Egypt, consistent with a proposed origin of domesticated barley in the Upper Jordan Valley. Our findings suggest that barley landraces grown in present-day Israel have not experienced major lineage turnover over the past six millennia, although there is evidence for gene flow between cultivated and sympatric wild populations. We demonstrate the usefulness of ancient genomes from desiccated archaeobotanical remains in informing research into the origin, early domestication and subsequent migration of crop species.
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http://dx.doi.org/10.1038/ng.3611DOI Listing
September 2016