Biology subjects

Krause, J.

Publications and source records attributed to Krause, J..

At least 55 records · Page 3Linked to original sources

bioRxiv2020

Ancient bacterial genomes reveal a formerly unknown diversity of Treponema pallidum strains in early modern Europe

Sexually transmitted (venereal) syphilis marked European history with a devastating epidemic at the end of the 15th century, and is currently re-emerging globally. Together with non-venereal treponemal diseases, like bejel and yaws, found in subtropical and tropical regions, it poses a prevailing health threat worldwide. The origins and spread of treponemal diseases remain unresolved, including syphilis potential introduction into Europe from the Americas. Here, we present the first genetic data from archaeological human remains reflecting a previously unknown diversity of Treponema pallidum in historical Europe. Our study demonstrates that a variety of strains related to both venereal syphilis and yaws were already present in Northern Europe in the early modern period. We also discovered a previously unknown T. pallidum lineage recovered as a sister group to yaws and bejel. These findings imply a more complex pattern of geographical prevalence and etiology of early treponemal epidemics than previously understood.

genetics↗

bioRxiv2020

A systematic investigation of human DNA preservation in medieval skeletons

Ancient DNA (aDNA) analyses necessitate the destructive sampling of archaeological material. Currently the dense inner portion of the petrous pyramid, the location of the skull that houses the inner ear, is the most sought after skeletal element for molecular analyses of ancient humans as it has been shown to yield high amounts of endogenous DNA. Destructive sampling of the petrous pyramid, assuming its recovery, is often not recommended for highly valued specimens. To investigate alternatives, we present a survey of human aDNA preservation for each of ten skeletal elements in a skeletal collection from Medieval Germany. Through comparison of human DNA content and quality we confirm best performance of the petrous pyramid and identify seven additional sampling locations across four skeletal elements that yield adequate aDNA for most applications in human palaeogenetics. Our study provides a better perspective on DNA preservation across the human skeleton and takes a further step toward the more responsible use of ancient materials in human aDNA studies.

molecular biology↗

bioRxiv2020

Tissue-specific multiOMICs analysis of atrial fibrillation

Genome-wide association studies (GWAS) for atrial fibrillation (AF) have uncovered numerous disease-associated variants. Their underlying molecular mechanisms, especially consequences for mRNA and protein expression remain largely elusive. Thus, novel multiOMICs approaches are needed for deciphering the underlying molecular networks. Here, we integrated genomics, transcriptomics, and proteomics of human atrial tissue which allowed for identifying widespread effects of genetic variants on both transcript (cis eQTL) and protein (cis pQTL) abundance. We further established a novel targeted trans QTL approach based on polygenic risk scores to identify candidates for AF core genes. Using this approach, we identified two trans eQTLs and four trans pQTLs for AF GWAS hits, and elucidated the role of the transcription factor NKX2-5 as a link between the GWAS SNP rs9481842 and AF. Altogether, we present an integrative multiOMICs method to uncover trans-acting networks in small datasets and provide a rich resource of atrial tissue-specific regulatory variants for transcript and protein levels for cardiovascular disease gene prioritization.

genetics↗

bioRxiv2020

A dynamic 6,000-year genetic history of Eurasia's Eastern Steppe

The Eastern Eurasian Steppe was home to historic empires of nomadic pastoralists, including the Xiongnu and the Mongols. However, little is known about the regions population history. Here we reveal its dynamic genetic history by analyzing new genome-wide data for 214 ancient individuals spanning 6,000 years. We identify a pastoralist expansion into Mongolia ca. 3000 BCE, and by the Late Bronze Age, Mongolian populations were biogeographically structured into three distinct groups, all practicing dairy pastoralism regardless of ancestry. The Xiongnu emerged from the mixing of these populations and those from surrounding regions. By comparison, the Mongols exhibit much higher Eastern Eurasian ancestry, resembling present-day Mongolic-speaking populations. Our results illuminate the complex interplay between genetic, sociopolitical, and cultural changes on the Eastern Steppe.

genomics↗

bioRxiv2020

Genomic and dietary transitions during the Mesolithic and Early Neolithic in Sicily

Southern Italy is a key region for understanding the agricultural transition in the Mediterranean due to its central position. We present a genomic transect for 19 prehistoric Sicilians that covers the Early Mesolithic to Early Neolithic period. We find that the Early Mesolithic hunter-gatherers (HGs) are a highly drifted sister lineage to Early Holocene western European HGs, whereas a quarter of the Late Mesolithic HGs ancestry is related to HGs from eastern Europe and the Near East. This indicates substantial gene flow from (south-)eastern Europe between the Early and Late Mesolithic. The Early Neolithic farmers are genetically most similar to those from the Balkan and Greece, and carry only a maximum of [~]7% ancestry from Sicilian Mesolithic HGs. Ancestry changes match changes in dietary profile and material culture, except for two individuals who may provide tentative initial evidence that HGs adopted elements of farming in Sicily. One-sentence summaryGenome-wide and isotopic data from prehistoric Sicilians reveal a pre-farming connection to (south-) eastern Europe, and tentative initial evidence that hunter-gatherers adopted some Neolithic aspects prior to near-total replacement by early farmers.

genetics↗

bioRxiv2020

African swine fever virus-like integrated elements in a soft tick genome - an ancient virus vector arms race?

BackgroundAfrican swine fever virus (ASFV) is the only known DNA-arbovirus and a most devastating suid pathogen that, originating from a sylvatic cycle in Africa, has spread to eastern Europe and recently reached western Europe and Asia, leading to a socio-economic crisis of global proportion. However, since neither closely related viruses nor integrated viral elements have yet been identified, ASFV evolution remains a mystery. ResultsHere, we show that soft ticks of the Ornithodoros moubata group, the natural arthropod vector of ASFV, harbour African swine fever virus-like integrated (ASFLI)-elements corresponding to up to 10% (over 20 kb) of the ASFV genome. Through orthologous dating and molecular clock analyses, we provide data suggesting that integration occurred over 1.47 million years ago. Furthermore, our data indicate that these elements, showing high sequence identities to modern ASFV, are maintained in the tick genome to protect the tick from infection with specific ASFV-strains through RNA interference. ConclusionWe suggest that this mechanism of protection, shaped through many years of co-evolution, is part of an evolutionary virus-vector "arms race", a finding that has not only high impact on our understanding of the co-evolution of viruses with their hosts but also provides a glimpse into the evolution of ASFV.

microbiology↗

bioRxiv2020

Consistent behavioural syndromes across seasons in an invasive freshwater fish

Understanding the linkage between behavioral types and dispersal tendency has become a pressing issue in light of global change and biological invasions. Here, we explore whether dispersing individuals exhibit behavioral types that differ from those remaining in the source population. We investigated a feral population of guppies (Poecilia reticulata) that undergoes a yearly range shift cycle. Guppies are among the most widespread invasive species in the world, but in temperate regions these tropical fish can only survive in winter-warm freshwaters. Established in a thermally-altered stream in Germany, guppies are confined to a warm-water influx in winter, but can spread to peripheral parts as these become thermally accessible. We sampled fish from the source population and a winter-abandoned site in March, June and August. Fish were tested for boldness, sociability and activity involving open-field tests including interactions with a robotic social partner. Guppies differed consistently among each other in all three traits. Behavioral trait expression in the source population differed across seasons, however, we could not detect differences between source and downstream populations. Instead, all sampled populations exhibited a remarkably stable behavioral syndrome between boldness and activity despite strong seasonal changes in water temperature and associated environmental factors. We conclude that random drift (opposed to personality-biased dispersal) is a more likely dispersal mode for guppies, at least in the investigated stream. In the face of fluctuating environments, guppies seem to be extremely effective in keeping behavioral expressions constant, which could help explain their successful invasion and adaptation to disturbed habitats.Competing Interest StatementThe authors have declared no competing interest.View Full Text

animal behavior and cognition↗

bioRxiv2019

Neolithic genomes reveal a distinct ancient HLA allele pool and population transformation in Europe

The Wartberg culture (WBC, 3,500-2,800 BCE) dates to the Late Neolithic period, a time of important demographic and cultural transformations in western Europe. We perform a genome-wide analysis of 42 individuals who were interred in a WBC collective burial in Niedertiefenbach, Germany (3,300-3,200 cal. BCE). Our results highlight that the Niedertiefenbach population indeed emerged at the beginning of the WBC. This farming community was genetically heterogeneous and carried a surprisingly large hunter-gatherer ancestry component (40%). We detect considerable differences in the human leukocyte antigen gene pool between contemporary Europeans and the Niedertiefenbach individuals whose immune response was primarily geared towards defending viral infections.

evolutionary biology↗

bioRxiv2019

Pan-cancer image-based detection of clinically actionable genetic alterations

Precision treatment of cancer relies on genetic alterations which are diagnosed by molecular biology assays.1 These tests can be a bottleneck in oncology workflows because of high turnaround time, tissue usage and costs.2 Here, we show that deep learning can predict point mutations, molecular tumor subtypes and immune-related gene expression signatures3,4 directly from routine histological images of tumor tissue. We developed and systematically optimized a one-stop-shop workflow and applied it to more than 4000 patients with breast5, colon and rectal6, head and neck7, lung8,9, pancreatic10, prostate11 cancer, melanoma12 and gastric13 cancer. Together, our findings show that a single deep learning algorithm can predict clinically actionable alterations from routine histology data. Our method can be implemented on mobile hardware14, potentially enabling point-of-care diagnostics for personalized cancer treatment in individual patients.

genetics↗

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

Population history from the Neolithic to present on the Mediterranean island of Sardinia: An ancient DNA perspective

Recent ancient DNA studies of western Eurasia have revealed a dynamic history of admixture, with evidence for major migrations during the Neolithic and Bronze Age. The population of the Mediterranean island of Sardinia has been notable in these studies - Neolithic individuals from mainland Europe cluster more closely with Sardinian individuals than with all other present-day Europeans. The current model to explain this result is that Sardinia received an initial influx of Neolithic ancestry and then remained relatively isolated from expansions in the later Neolithic and Bronze Age that took place in continental Europe. To test this model, we generated genome-wide capture data (approximately 1.2 million variants) for 43 ancient Sardinian individuals spanning the Neolithic through the Bronze Age, including individuals from Sardinias Nuragic culture, which is known for the construction of numerous large stone towers throughout the island. We analyze these new samples in the context of previously generated genome-wide ancient DNA data from 972 ancient individuals across western Eurasia and whole-genome sequence data from approximately 1,500 modern individuals from Sardinia. The ancient Sardinian individuals show a strong affinity to western Mediterranean Neolithic populations and we infer a high degree of genetic continuity on the island from the Neolithic (around fifth millennium BCE) through the Nuragic period (second millennium BCE). In particular, during the Bronze Age in Sardinia, we do not find significant levels of the \"Steppe\" ancestry that was spreading in many other parts of Europe at that time. We also characterize subsequent genetic influx between the Nuragic period and the present. We detect novel, modest signals of admixture between 1,000 BCE and present-day, from ancestry sources in the eastern and northern Mediterranean. Within Sardinia, we confirm that populations from the more geographically isolated mountainous provinces have experienced elevated levels of genetic drift and that northern and southwestern regions of the island received more gene flow from outside Sardinia. Overall, our genetic analysis sheds new light on the origin of Neolithic settlement on Sardinia, reinforces models of genetic continuity on the island, and provides enhanced power to detect post-Bronze-Age gene flow. Together, these findings offer a refined demographic model for future medical genetic studies in Sardinia.

genetics↗

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

Proteome thermal stability reflects organ physiology and identifies drug-target engagement in vivo

Studying biological processes at a molecular level and monitoring drug-target interactions is established for simple cell systems but challenging in vivo. We introduce and apply a methodology for proteome-wide thermal stability measurements to characterize organ physiology and activity of many fundamental biological processes across tissues, such as energy metabolism and protein homeostasis. This method, termed tissue thermal proteome profiling (tissue-TPP), also enabled target and off-target identification and occupancy measurements in tissues derived from animals dosed with the non-covalent histone deacetylase inhibitor, panobinostat. Finally, we devised blood-CETSA, a thermal stability-based method to monitor target engagement in whole blood. Our study generates the first proteome-wide map of protein thermal stability in tissue and provides tools that will be of great impact for translational research.

cell biology↗

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

Females facilitate male patch discovery in a wild fish population

When individuals are more socially responsive to one sex than the other, the benefits they get from foraging socially are likely to depend on the sex composition of the social environment. We tested this hypothesis by performing experimental manipulations of guppy, Poecilia reticulata, sex compositions in the wild. Males found fewer novel food patches in the absence of females than in mixed-sex compositions, while female patch discovery did not differ between compositions. We argue that these results were driven by sex-dependent mechanisms of social association: Markov chain-based fission-fusion modeling revealed that males reduced sociality when females were absent, while less social individuals found fewer patches. Females were similarly social with or without males. Finally, males, but not females, preferred to join females over males at patches. Our findings reveal the relevance of considering how individual and population-level traits interact in shaping the adaptive value of social living in the wild.

animal behavior and cognition↗

bioRxiv2018

Social networks in the presence and absence of visual cues

We compared the social dynamics of two populations of the live-bearing Atlantic molly (Poecilia mexicana) that live in adjacent habitats with very different predator regimes: cave mollies that inhabit a low-predation environment inside a sulfidic cave with a low density of predatory water bugs (Belostoma sp.), and mollies that live directly outside the cave (henceforth called \"surface\" mollies) in a high-predation environment with a high density of fish-eating birds. We filmed the social interactions of marked fish in both environments and analysed their social network dynamics using a Markov model under two different fish densities of 12 and 6 fish per 0.36 m2. As expected, surface mollies spent overall much more time social than cave mollies. This difference in overall social time was a result of surface mollies being less likely to discontinue social contact (once they had a social partner) and being more likely to resume social contact (once alone) than cave mollies. Interestingly surface mollies were also less likely to leave a current social partner than cave mollies. At low density, mollies (in both environments) were expected to show reduced social encounters which should dramatically change their social dynamics. Surface mollies, however, displayed an ability to maintain their social dynamics at low density (primarily by reducing the convex polygon spanned by the group) which was not observed in cave mollies. Despite the fact that we only compared two populations, our data provide a mechanistic explanation for density compensations of social dynamics that have also been observed in other fish species and give an example of how comparisons between the social dynamics of different populations can be made that go beyond conventional network analyses.

animal behavior and cognition↗

bioRxiv2018

Late Pleistocene human genome suggests a local origin for the first farmers of central Anatolia

Anatolia was home to some of the earliest farming communities. It has been long debated whether a migration of farming groups introduced agriculture to central Anatolia. Here, we report the first genome-wide data from a 15,000-year-old Anatolian hunter-gatherer and from seven Anatolian and Levantine early farmers. We find high genetic continuity ([~]80-90%) between the hunter-gatherer and early farmers of Anatolia and detect two distinct incoming ancestries: an early Iranian/Caucasus related one and a later one linked to the ancient Levant. Finally, we observe a genetic link between southern Europe and the Near East predating 15,000 years ago that extends to central Europe during the post-last-glacial maximum period. Our results suggest a limited role of human migration in the emergence of agriculture in central Anatolia.

genetics↗