Biology subjects

Herbig, A.

Publications and source records attributed to Herbig, A..

16 recordsLinked to original sources

bioRxiv2025

Temporal foundation model unveils ancient HepatitisB virus evolution

Since ancient hepatitis B virus (HBV) sequencing data are scarce and incomplete, the evolutionary dynamics of HBV have long remained enigmatic. This data gap hinders a comprehensive understanding of HBV genetic variations, evolutionary trajectories, and host interactions in different historical periods, preventing insight into its long-standing co-evolutionary relationship with humans. In this study, we developed a sequence-based generative foundational model, ViraChron (Viral Chronology Foundation Model), that integrates multi-scale temporal information to compensate for the lack of ancient HBV data. We confirmed the robustness of our model through sequence identity, phylogenetic, and recombination analyses. ViraChron enabled the identification of fixed mutations specific to HBV genotype A, demonstrating that HBV acquires survival advantages through mutations that are ultimately fixed by natural selection. Our model outperforms the original baseline in terms of sequence completion, achieving significantly higher accuracy. The model significantly reduced data acquisition time from 80 hours to 5.4 minutes per HBV genome, providing reliable, high-quality data for 7 new HBV genomes from specific archeological sites. ViraChron overcomes previous limitations, obtaining high-quality genomic data from samples over ten thousand years old, thereby facilitating a systematic understanding of viral evolution and its biological characteristics.

paleontology↗

bioRxiv2025

TSSpredator-Web: A web-application for transcription start site prediction and exploration

BackgroundWith the rapid development of high-throughput RNA-seq technologies, the transcriptome of prokaryotes can now be studied in unprecedented detail. Transcription start site (TSS) identification provides critical insights into transcriptional regulation, yet current command-line tools for the prediction of TSS remain challenging with respect to their usability and lack of integrated exploration features. ResultsWe introduce TSSpredator-Web an interactive web application that enhances the usability of the established yet unpublished tool, TSSpredator. TSSpredator-Web facilitates TSS prediction from non-enriched and enriched RNA-seq data, classifies TSS relative to annotated genes, and allows users to explore results through dynamic visualizations and interactive tables. For the visualizations we provide an UpSet plot summarizing TSS distribution across experiments or classes, and a genome viewer that integrates transcriptomic and genomic data that contextualizes the insights of the TSS predictions. To illustrate the usage of TSSpredator-Web, we provide a use case with Cappable-seq data from Escherichia coli. TSSpredator-Web is available at the TueVis visualization web-server at https://tsspredator-tuevis.cs.uni-tuebingen.de/. ConclusionsBy combining user-friendly accessibility with interactive data exploration, TSSpredator-Web significantly facilitates genome-wide TSS analysis and interpretation in prokaryotes, empowering a broader range of researchers to generate biological insights from transcriptomic data.

bioinformatics↗

bioRxiv2025

Bronze Age Yersinia pestis genome from sheep sheds light on hosts and evolution of a prehistoric plague lineage

Most human pathogens are of zoonotic origin. Many emerged during prehistory, coinciding with domestication providing more opportunities for spillover from original host species. However, we lack direct evidence linking past animal reservoirs and human infections. Here we present a Yersinia pestis genome recovered from a 3rd millennium BCE domesticated sheep from the Eurasian Steppe belonging to the Late Neolithic Bronze Age (LNBA) lineage, until now exclusively identified in ancient humans across Eurasia. We show that this ancient lineage underwent ancestral gene decay paralleling extant lineages, but evolved under distinct selective pressures contributing to its lack of geographic differentiation. We collect evidence supporting a scenario where the LNBA lineage, unable to efficiently transmit via fleas, spread from an unidentified reservoir to humans via sheep and likely other domesticates. Collectively, our results connect prehistoric livestock with infectious disease in humans and showcase the power of moving paleomicrobiology into the zooarcheological record.

genetics↗

bioRxiv2022

Ancient herpes simplex 1 genomes reveal recent viral structure in Eurasia

Human herpes simplex virus 1 (HSV-1), a life-long infection spread by oral contact, today infects a majority of adults globally1, yet no ancient HSV-1 genomes have yet been published. Phylogeographic clustering of sampled diversity into European, pan-Eurasian, and African groups2, 3 has suggested that the virus co-diverged with anatomically modern humans migrating out of Africa4, although a much younger origin has also been proposed5. The lack of ancient HSV-1 genomes, high rates of recombination, and high mobility of humans in the modern era have impeded the understanding of HSV-1s evolutionary history. Here we present three full ancient European HSV-1 genomes and one partial genome, dating to between the 3rd and 17th century CE, sequenced to up to 9.5x with paired human genomes up to 10.16x. These HSV-1 strains fall within modern Eurasian diversity. We estimate a mean mutation rate of 7.6 x 10-7 - 1.13 x 10-6 for non-African diversity leading to an estimated age of sampled modern Eurasian diversity to 4.68 (3.87 - 5.65) kya. Extrapolation of these rates indicate the age of sampled HSV-1 to 5.29 (4.60-6.12 kya, suggesting lineage replacement coinciding with late Neolithisation and implicating Bronze Age migrations6 in the distribution of HSV-1 through Eurasia.

genomics↗

bioRxiv2021

Synergistic coevolution accelerates genome evolution

Ecological interactions are key drivers of evolutionary change. Although it is well-documented that antagonistic coevolution can accelerate molecular evolution, the evolutionary consequences of synergistic coevolution remain poorly understood. Here we show experimentally that also synergistic coevolution can speed up the rate of molecular evolution. Pairs of auxotrophic genotypes of the bacterium Escherichia coli, whose growth depended on a reciprocal exchange of amino acids, were experimentally coevolved, and compared to two control groups of independently growing cells. Coevolution drove the rapid emergence of a strong metabolic cooperation that correlated with a significantly increased number of mutations in coevolved auxotrophs as compared to monoculture controls. These results demonstrate that synergistic coevolution can cause rapid evolution that in the long run may drive diversification of mutualistically interacting species. One-Sentence SummarySynergistic coevolution among obligate mutualists increases the rate of molecular evolution relative to independent types.

evolutionary biology↗

bioRxiv2021

Using Y-chromosome capture enrichment to resolve haplogroup H2 shows new evidence for a two-Path Neolithic expansion to Western Europe

Uniparentally-inherited markers on mitochondrial DNA (mtDNA) and the non-recombining regions of the Y chromosome (NRY), have been used for the past 30 years to investigate the history of humans from a maternal and paternal perspective. Researchers have preferred mtDNA due to its abundance in the cells, and comparatively high substitution rate. Conversely, the NRY is less susceptible to back mutations and saturation, and is potentially more informative than mtDNA owing to its longer sequence length. However, due to comparatively poor NRY coverage via shotgun sequencing, and the relatively low and biased representation of Y-chromosome variants on capture arrays such as the 1240K, ancient DNA studies often fail to utilize the unique perspective that the NRY can yield. Here we introduce a new DNA enrichment assay, coined YMCA (Y-mappable capture assay), that targets the "mappable" regions of the NRY. We show that compared to low-coverage shotgun sequencing and 1240K capture, YMCA significantly improves the coverage and number of sites hit on the NRY, increasing the number of Y-haplogroup informative SNPs, and allowing for the identification of previously undiscovered variants. To illustrate the power of YMCA, we show that the analysis of ancient Y-chromosome lineages can help to resolve Y-chromosomal haplogroups. As a case study, we focus on H2, a haplogroup associated with a critical event in European human history: the Neolithic transition. By disentangling the evolutionary history of this haplogroup, we further elucidate the two separate paths by which early farmers expanded from Anatolia and the Near East to western Europe.

genetics↗

bioRxiv2019

CoproID predicts the source of coprolites and paleofeces using microbiome composition and host DNA content

Shotgun metagenomics applied to archaeological feces (paleofeces) can bring new insights into the composition and functions of human and animal gut microbiota from the past. However, paleofeces often undergo physical distortions in archaeological sediments, making their source species difficult to identify on the basis of fecal morphology or microscopic features alone. Here we present a reproducible and scalable pipeline using both host and microbial DNA to infer the host source of fecal material. We apply this pipeline to newly sequenced archaeological specimens and show that we are able to distinguish morphologically similar human and canine paleofeces, as well as non-fecal sediments, from a range of archaeological contexts.

microbiology↗

bioRxiv2019

Ancient Yersinia pestis genomes provide no evidence for the origins or spread of the Justinianic Plague

Along with the publication of 137 ancient human genomes retrieved from archaeological remains of the Eurasian steppe, Damgaard et al., 2018 identified two individuals infected with Yersinia pestis, yielding one genome with 0.24x average coverage (DA147, 6th-9th c. AD) and another with 8.7x (DA101, 2nd-3rd c. AD). A phylogenetic analysis performed on the latter placed it in a position ancestral to a 6th-century Justinianic genome from Aschheim, Germany. These results are used to fuel an argument that the Justinianic Plague (541-544 AD) "was brought to Europe towards the end of the Hunnic period through the Silk Road along the southern fringes of the steppes" in contrast to the leading hypothesis of introduction via the Red Sea that is supported by historical accounts. In our reanalysis, we question the contested historical context of the presented genomes with the Justinianic Plague and show that the lower coverage genome might be rather related to the Black Death (1346-1353 AD).

evolutionary biology↗

bioRxiv2019

A seventeenth-century Mycobacterium tuberculosis genome supports a Neolithic emergence of the Mycobacterium tuberculosis complex

BackgroundAlthough tuberculosis accounts for the highest mortality from a bacterial infection on a global scale, questions persist regarding its origin. One hypothesis based on modern Mycobacterium tuberculosis complex (MTBC) genomes suggests their most recent common ancestor (MRCA) followed human migrations out of Africa ~70,000 years before present (BP). However, studies using ancient genomes as calibration points have yielded much younger MRCA dates of less than 6,000 years. Here we aim to address this discrepancy through the analysis of the highest-coverage and highest quality ancient MTBC genome available to date, reconstructed from a calcified lung nodule of Bishop Peder Winstrup of Lund (b. 1605 - d. 1697).\n\nResultsA metagenomic approach for taxonomic classification of whole DNA content permitted the identification of abundant DNA belonging to the human host and the MTBC, with few non-TB bacterial taxa comprising the background. Subsequent genomic enrichment enabled the reconstruction of a 141-fold coverage M. tuberculosis genome. In utilizing this high-quality, high-coverage 17th century M. tuberculosis genome as a calibration point for dating the MTBC, we employed multiple Bayesian tree models, including birth-death models, which allowed us to model pathogen population dynamics and data sampling strategies more realistically than those based on the coalescent.\n\nConclusionsThe results of our metagenomic analysis demonstrate the unique preservation environment calcified nodules provide for DNA. Importantly, we estimate an MRCA date for the MTBC of 3683 BP (2253-5821 BP) and for Lineage 4 of 1651 BP (946-2575 BP) using multiple models, confirming a Neolithic emergence for the MTBC.

genomics↗

bioRxiv2019

HOPS: Automated detection and authentication of pathogen DNA in archaeological remains

High-throughput DNA sequencing enables large-scale metagenomic analyses of complex biological systems. Such analyses are not restricted to present day environmental or clinical samples, but can also be fruitfully applied to molecular data from archaeological remains (ancient DNA), and a focus on ancient bacteria can provide valuable information on the long-term evolutionary relationship between hosts and their pathogens. Here we present HOPS (Heuristic Operations for Pathogen Screening), an automated bacterial screening pipeline for ancient DNA sequence data that provides straightforward and reproducible information on species identification and authenticity. HOPS provides a versatile and fast pipeline for high-throughput screening of bacterial DNA from archaeological material to identify candidates for subsequent genomic-level analyses.

bioinformatics↗

bioRxiv2018

A phylogeography of the second plague pandemic revealed through the analysis of historical Y. pestis genomes

The second plague pandemic (14th - 18th century AD), caused by the bacterium Yersinia pestis, is infamous for its initial wave, the Black Death (1346-1353 AD), and its repeated scourges in Europe and the vicinity until the Early Modern Era. Here, we report 32 ancient Y. pestis genomes spanning the 14th to 17th century AD through the analysis of human remains from nine European archaeological sites. Our data support an initial entry of the bacterium from Eastern Europe and the absence of genetic diversity during the Black Death as well as low diversity during local outbreaks thereafter. Moreover, analysis of post-Black Death genomes shows the diversification of a Y. pestis lineage into multiple genetically distinct clades that may have given rise to more than one disease reservoir in, or close to, Europe. Finally, we show the loss of a genomic region that includes virulence-associated genes in strains associated with late stages of the second plague pandemic (17th - 18th century AD). This deletion could not be detected in extant strains within our modern dataset, though it was identified in a today-extinct lineage associated with the first plague pandemic (6th - 8th century AD), suggesting convergent evolution during both pandemic events.

evolutionary biology↗

bioRxiv2018

Ancient Yersinia pestis genomes from across Western Europe reveal early diversification during the First Pandemic (541-750)

The first historically documented pandemic caused by Yersinia pestis started as the Justinianic Plague in 541 within the Roman Empire and continued as the so-called First Pandemic until 750. Although palaeogenomic studies have previously identified the causative agent as Y. pestis, little is known about the bacteriums spread, diversity and genetic history over the course of the pandemic.\n\nTo elucidate the microevolution of the bacterium during this time period, we screened human remains from 20 sites in Austria, Britain, Germany, France and Spain for Y. pestis DNA and reconstructed six new genomes. We present a novel methodological approach assessing SNPs in ancient bacterial genomes, facilitating qualitative analyses of low coverage genomes from a metagenomic background. Phylogenetic analysis reveals the existence of previously undocumented Y. pestis diversity during the 6th-7th centuries, and provides evidence for the presence of multiple distinct Y. pestis strains in Europe. We offer genetic evidence for the presence of the Justinianic Plague in the British Isles, previously only hypothesized from ambiguous documentary accounts, as well as southern France and Spain, and that southern Germany seems to have been affected by at least two distinct Y. pestis strains. Four of the reported strains form a polytomy similar to others seen across the Y. pestis phylogeny, associated with the Second and Third Pandemics. We identified a deletion of a 45 kb genomic region in the most recent First Pandemic strain affecting two virulence factors, intriguingly overlapping with a deletion found in 17th-18th-century genomes of the Second Pandemic.\n\nSignificance StatementThe first historically reported pandemic attributed to Yersinia pestis started with the Justinianic Plague (541-544) and continued for around 200 years as the so-called First Pandemic. To date, only one Y. pestis strain from this pandemic has been reconstructed using ancient DNA. In this study, we present six new genomes from Britain, France, Germany and Spain, demonstrating the geographic range of plague during the First pandemic and showing microdiversity in the Early Medieval Period. Moreover, we detect similar genome decay during the First and Second Pandemic (17th to 18th century) that includes the same two virulence factors, thus providing an example of potential convergent evolution of Y. pestis during large scale epidemics.

evolutionary biology↗

bioRxiv2018

Neolithic and Medieval virus genomes reveal complex evolution of Hepatitis B

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 genomes by de novo assembly from shotgun DNA sequencing data. Additionally, we observed HBV-specific peptides using paleo-proteomics. Our results show that HBV circulates 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. These ancient virus forms appear to represent distinct lineages that have no close relatives today and went possibly 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.

evolutionary biology↗

bioRxiv2018

Selection of appropriate metagenome taxonomic classifiers for ancient microbiome research

Metagenomics enables the study of complex microbial communities from myriad sources, including the remains of oral and gut microbiota preserved in archaeological dental calculus and paleofeces, respectively. While accurate taxonomic assignment is essential to this process, DNA damage, characteristic to ancient samples (e.g. reduction in fragment size), may reduce the accuracy of read taxonomic assignment. Using a set of in silico-generated metagenomic datasets we investigated how the addition of ancient DNA (aDNA) damage patterns influences microbial taxonomic assignment by five widely-used profilers: QIIME/UCLUST, MetaPhlAn2, MIDAS, CLARK-S, and MALT (BLAST-X-mode). In silico-generated datasets were designed to mimic dental plaque, consisting of 40, 100, and 200 microbial species/strains, both with and without simulated aDNA damage patterns. Following taxonomic assignment, the profiles were evaluated for species presence/absence, relative abundance, alpha-diversity, beta-diversity, and specific taxonomic assignment biases. Unifrac metrics indicated that both MIDAS and MetaPhlAn2 provided the most accurate community structure reconstruction. QIIME/UCLUST, CLARK-S, and MALT had the highest number of inaccurate taxonomic assignments; however, filtering out species present at <0.1% abundance greatly increased the accuracy of CLARK-S and MALT. All programs except CLARK-S failed to detect some species from the input file that were in their databases. Ancient DNA damage resulted in minimal differences in species detection and relative abundance between simulated ancient and modern datasets for most programs. In conclusion, taxonomic profiling biases are program-specific rather than damage-dependent, and the choice of taxonomic classification program to use should be tailored to the research question.\n\nImportanceAncient biomolecules from oral and gut microbiome samples have been shown to preserve in the archaeological record. Studying ancient microbiome communities using metagenomic techniques offer a unique opportunity to reconstruct the evolutionary trajectories of microbial communities through time. DNA accumulates specific damage over time, which could potentially affect taxonomic classification and our ability to reconstruct community assemblages accurately. It is therefore necessary to assess whether ancient DNA (aDNA) damage patterns affect metagenomic taxonomic profiling. Here, we assessed biases in community structure, diversity, species detection, and relative abundance estimates by five popular metagenomic taxonomic classification programs using in silico-generated datasets with aDNA damage. Age-related damage patterns had minimal impact on the taxonomic profiles produced by each program, and biases were intrinsic to each program. Therefore, an appropriate classification program should be chosen that minimizes the biases related to the questions being addressed.

microbiology↗

bioRxiv2017

Salmonella enterica genomes recovered from victims of a major 16th century epidemic in Mexico

Indigenous populations of the Americas experienced high mortality rates during the early contact period as a result of infectious diseases, many of which were introduced by Europeans. Most of the pathogenic agents that caused these outbreaks remain unknown. Using a metagenomic tool called MALT to search for traces of ancient pathogen DNA, we were able to identify Salmonella enterica in individuals buried in an early contact era epidemic cemetery at Teposcolula-Yucundaa, Oaxaca in southern Mexico. This cemetery is linked to the 1545-1550 CE epidemic locally known as \"cocoliztli\", the cause of which has been debated for over a century. Here we present two reconstructed ancient genomes for Salmonella enterica subsp. enterica serovar Paratyphi C, a bacterial cause of enteric fever. We propose that S. Paratyphi C contributed to the population decline during the 1545 cocoliztli outbreak in Mexico.\n\nOne Sentence SummaryGenomic evidence of enteric fever identified in an indigenous population from early contact period Mexico.

genomics↗

bioRxiv2016

The Stone Age Plague: 1000 years of Persistence in Eurasia

Molecular signatures of Yersinia pestis were recently identified in prehistoric Eurasian individuals, thus suggesting Y. pestis caused some form of disease in humans prior to the first historically documented pandemic. Here, we present six new Y. pestis genomes spanning from the European Late Neolithic to the Bronze Age (LNBA) dating from 4,800 to 3,700 BP. We show that all currently investigated LNBA strains form a single genetic clade in the Y. pestis phylogeny that appears to be extinct. Interpreting our data within the context of recent ancient human genomic evidence, which suggests an increase in human mobility during the LNBA, we propose a possible scenario for the spread of Y. pestis during the LNBA: Y. pestis may have entered Europe from Central Eurasia during an expansion of steppe people, persisted within Europe until the mid Bronze Age, and moved back towards Central Eurasia in parallel with subsequent human population movements.

evolutionary biology↗