On Roth's "human fossil" from Baradero, Buenos Aires Province, Argentina: morphological and genetic analysis.

The "human fossil" from Baradero, Buenos Aires Province, Argentina, is a collection of skeleton parts first recovered by the paleontologist Santiago Roth and further studied by the anthropologist Rudolf Martin. By the end of the nineteenth century and beginning of the twentieth century it was considered one of the oldest human skeletons from South America's southern cone. Here, we present the results of an interdisciplinary approach to study and contextualize the ancient individual remains. We discuss the context of the finding by first compiling the available evidence associated with the historical information and any previous scientific publications on this individual. Then, we conducted an osteobiographical assessment, by which we evaluated the sex, age, and overall preservation of the skeleton based on morphological features. To obtain a 3D virtual reconstruction of the skull, we performed high resolution CT-scans on selected skull fragments and the mandible. This was followed by the extraction of bone tissue and tooth samples for radiocarbon and genetic analyses, which brought only limited results due to poor preservation and possible contamination. We estimate that the individual from Baradero is a middle-aged adult male. We conclude that the revision of foundational collections with current methodological tools brings new insights and clarifies long held assumptions on the significance of samples that were recovered when archaeology was not yet professionalized.

Non-destructive extraction of DNA from preserved tissues in medical collections.

Museum specimens and histologically fixed material are valuable samples for the study of historical soft tissues and represent a possible pathogen-specific source for retrospective molecular investigations. However, current methods for molecular analysis are inherently destructive, posing a dilemma between performing a study with the available technology, thus damaging the sample, and conserving the material for future investigations. Here the authors present the first tests of a non-destructive alternative that facilitates genetic analysis of fixed wet tissues while avoiding tissue damage. The authors extracted DNA from the fixed tissues as well as their embedding fixative solution, to quantify the DNA that was transferred to the liquid component. The results show that human historical DNA can be retrieved from the fixative material of medical specimens and provide new options for sampling valuable collections.

Metagenomic analysis of Ancient Egyptian canopic jars.

Ancient Egyptian remains have been of interest for anthropological research for decades. Despite many investigations, the ritual vessels for the internal organs removed during body preparation-liver, lungs, stomach, and intestines, of Egyptian mummies are rarely used for palaeopathological or medical investigations. These artifacts, commonly referred to as canopic jars, are the perfect combination of cultural and biological material and present an untapped resource for both Egyptological and medical fields. Nevertheless, technical challenges associated with this archeological material have prevented the application of current ancient DNA techniques for both the characterization of human and pathogenic DNA. We present shotgun-sequenced metagenomic profiles and ancient DNA degradation patterns from multiple canopic jars sampled from several European museum collections and enumerate current limitations and possible solutions for the future analysis of similar material. This is the first-ever recorded evidence of ancient human DNA found in Ancient Egyptian canopic jars and the first associated metagenomic description of bacterial taxa in these funerary artifacts. OBJECTIVES: In this study, our objectives were to characterize the metagenomic profile of the Ancient Egyptian funerary vessels known as canopic jars to retrieve endogenous ancient human DNA, reconstruct ancient microbial communities, and identify possible pathogens that could shed light on disease states of individuals from the past. METHODS: We applied ancient DNA techniques on 140 canopic jars to extract DNA and generate whole-genome sequencing libraries for the analysis of both human and bacterial DNA. The samples were obtained from museum collections in Berlin (DE), Burgdorf (DE), Leiden (NE), Manchester (UK), Munich (DE), St. Gallen (CH), Turin (IT), and Zagreb (HR). RESULTS: Here we describe the first isolated DNA from the Egyptian artifacts that hold human viscera. No previous work was ever conducted on such material, which led to the first characterization of human DNA from Ancient Egyptian canopic jars and the profiling of the complex bacterial composition of this highly degraded, challenging, organic material. However, the DNA recovered was not of enough quality to confidently characterize bacterial taxa associated with infectious diseases, nor exclusive bacterial members of the human microbiome. DISCUSSION: In summary, we present the first genomic survey of the visceral content of Ancient Egyptian funerary artifacts and demonstrate the limitations of current molecular methods to analyze canopic jars, such as the incomplete history of the objects or the presence of uncharacterized compounds that can hamper the recovery of DNA. Our work highlights the main challenges and caveats when working with such complicated archeological material - and offers sampling recommendations for similarly complex future studies, such as incrementing the amount of starting material and sampling from the less exposed parts of the jar content. This is the first-ever recorded evidence of ancient human DNA found in Ancient Egyptian canopic jars, and our results open new avenues in the study of neglected archeological artifacts.

A refined proposal for the origin of dogs: the case study of Gnirshöhle, a Magdalenian cave site.

Dogs are known to be the oldest animals domesticated by humans. Although many studies have examined wolf domestication, the geographic and temporal origin of this process is still being debated. To address this issue, our study sheds new light on the early stages of wolf domestication during the Magdalenian period (16-14 ka cal BP) in the Hegau Jura region (Southwestern Germany and Switzerland). By combining morphology, genetics, and isotopes, our multidisciplinary approach helps to evaluate alternate processes driving the early phases of domestication. The isotope analysis uncovered a restricted, low δ15N protein diet for all analyzed Gnirshöhle specimens, while morphological examinations and phylogenetic relationships did not unequivocally assign them to one or the other canid lineage. Intriguingly, the newly generated mitochondrial canid genomes span the entire genetic diversity of modern dogs and wolves. Such high mitochondrial diversity could imply that Magdalenian people tamed and reared animals originating from different wolf lineages. We discuss our results in light of three ecological hypotheses and conclude that both domestication and the existence of a specialized wolf ecomorph are highly probable. However, due to their proximity to humans and a restricted diet, we propose domestication as the most likely scenario explaining the patterns observed herein.

Variola virus genome sequenced from an eighteenth-century museum specimen supports the recent origin of smallpox.

Smallpox, caused by the variola virus (VARV), was a highly virulent disease with high mortality rates causing a major threat for global human health until its successful eradication in 1980. Despite previously published historic and modern VARV genomes, its past dissemination and diversity remain debated. To understand the evolutionary history of VARV with respect to historic and modern VARV genetic variation in Europe, we sequenced a VARV genome from a well-described eighteenth-century case from England (specimen P328). In our phylogenetic analysis, the new genome falls between the modern strains and another historic strain from Lithuania, supporting previous claims of larger diversity in early modern Europe compared to the twentieth century. Our analyses also resolve a previous controversy regarding the common ancestor between modern and historic strains by confirming a later date around the seventeenth century. Overall, our results point to the benefit of historic genomes for better resolution of past VARV diversity and highlight the value of such historic genomes from around the world to further understand the evolutionary history of smallpox as well as related diseases. This article is part of the theme issue 'Insights into health and disease from ancient biomolecules'.

Human cytomegalovirus activation of ERK and myeloid cell leukemia-1 protein correlates with survival of latently infected cells.

The ability of human CMV (HCMV) to enter and establish a latent infection in myeloid cells is crucial for survival and transmission in the human population. Initial pathogen binding and entry triggers a number of antiviral responses, including the activation of proapoptotic cell death pathways, which must be countered during latency establishment. However, mechanisms responsible for a prosurvival state in myeloid cells upon latent HCMV infection remain completely undefined. We hypothesized that the cellular antiapoptotic machinery must be initially activated by HCMV to promote early survival events upon entry. Here we show that HCMV transiently protects nonpermissive myeloid cells from chemical and virus entry induced cell death by up-regulating a key myeloid cell survival gene, myeloid cell leukemia (MCL)-1 protein. The induction of MCL-1 expression was independent of viral gene expression but dependent on activation of the ERK-MAPK pathway by viral glycoprotein B. Inhibition of ERK-MAPK signaling, inhibition of HCMV fusion, antibody-mediated neutralization of glycoprotein B signaling or expression of a shRNA against MCL-1 all correlated with increased cell death in response to virus infection or chemical stimulation. Finally we show that activation of ERK-MAPK signaling impacts on long-term latency and reactivation in hematopoietic cells. Thus, HCMV primes myeloid cells for from the initial virus-cell encounter. Given the importance of ERK and MCL-1 for myeloid cell survival, the successful establishment of HCMV latency in myeloid progenitors begins at the point of virus entry.