CRC 1266 - Scales of Transformation

Phase 1 - Research activities 2016-2020

F4: Tracing Infectious Diseases in Prehistoric Populations

Principal Investigators: Prof. Dr. Ben Krause-Kyora, Prof. Dr. Almut Nebel
Staff: Alexander Immel


Research agenda

Ancient DNA work performed in a clean lab
Fig. 1. Ancient DNA work must be performed in a clean lab to avoid contamination with exogenous DNA. Additional protective measures involve the use of overalls, masks and gloves. (photo: S. Kornell)

Infectious diseases are thought to have accompanied Homo sapiens throughout evolution. Many epidemiological changes may have taken place during important prehistorical and historical transformation processes. Project F4 aims to evaluate whether infectious diseases co-occurred with major prehistoric demographic and/or environmental crises. To this end, several hundred well-dated human skeletal remains will be screened for the presence of known bacterial and viral pathogens by capturing and sequencing their preserved genetic material with state-of-the-art molecular techniques. The obtained results will be compared with genomic data from present-day pathogens to develop models for the reconstruction of past and the prediction of modern epidemics.

DNA analysis calculus
Fig. 2. Dental calculus precipitated on the lower premolars and molars. Dental calculus mineralizes during the lifetime of an individual so that DNA is extremely well preserved. (photo: S. Kornell)

Infections are thought to have accompanied Homo sapiens throughout evolution, and many epidemics may have influenced important prehistoric transformation processes. Project F4 aims to evaluate whether pathogens co-occurred with major demographic and/or environmental crises in the past.

Results and research activities

Epidemics are thought to have influenced or triggered important prehistoric transformation processes. It has been hypothesized that especially the Neolithic transition was accompanied by a rise of infectious diseases, maybe even of epidemic proportions, due to substantial changes in human ecology, which in turn was influenced by housing conditions, hygiene, physical activity and diet. The initial aim of subproject F4 was to evaluate whether pathogens (blood-borne bacteria, viruses) co-occurred with major transformations that are the focus of the CRC, in particular in the Neolithic Period and the Bronze Age.

Large-scale pathogen screening of 731 Neolithic and Bronze Age skeletons for infectious microbial agents yielded - with the exception of Helicobacter pylori in the Iceman Ötzi (Maixner et al., 2016) and the hepatitis virus in two Neolithic specimens (Krause-Kyora et al., 2018 eLIFE) - no evidence of infectious agents. This result challenges the previous research hypothesis stated above. Our and other recent ancient DNA studies on pathogens confirmed only single infections throughout the Neolithic, but there is no evidence for outbreaks of epidemic proportions. In particular, we did not find any support for the hypothesis that migration of the Yamnaya people westward was accompanied by the transmission of Yersinia pestis, the causal agent of the plague (Immel et al. 2020).

With respect to potential ‘triggers and components of change’ in Neolithic Germany (with special focus on the loess zone), we reviewed the occurrence of pathogens together with archaeological and palaeopathological proxies (in cooperation with D2 and Z1). The comparison showed that major transformations in domestic strategies and mortuary practice did take place between 5500 and 2500 BCE, but evidence is missing for drawing a causal link between these changes and the presence of pathogens or indicators of skeletal pathology (Fuchs et al. 2019).

If pathogens are no longer detectable in old bones, the analysis of human immune genes can provide indirect inferences about infectious diseases in the past. We performed a small pilot study in which we analysed in detail the human leucocyte antigen (HLA) region. This region encompasses a large number of very important immune genes. First, we established a method for HLA gene capture and a bioinformatics pipeline that allowed us to reliably call the alleles in ancient DNA extracts (Krause-Kyora et al. 2018 Nature Communications; Pierini et al. 2020). In addition, we applied this method to determine the HLA profiles of a Neolithic community interred in the gallery grave from Niedertiefenbach, Germany (3300-3200 cal. BCE; Meadows et al. 2020; Rinne et al., 2019). We observed that the Niedertiefenbach population had an HLA gene pool that differed considerably from that of present-day Germans, suggesting substantial and enduring transformations in immune response over thousands of years (unpublished).

Since migrations may have played an important role in the emergence and spread of epidemics, another focus of F4 was on identifying demographic transformations by ancient genomics. In particular, in conjunction with D1, we showed that Cucuteni-Trypillia associated populations in present-day Moldova experienced gradual gene-flow from steppe individuals, maybe as early as 3500 BCE. This finding is in agreement with the hypothesis of ongoing contacts and gradual admixture between incoming steppe and local western populations (Immel et al., 2020). In another study, which was conducted in collaboration with D2 and Z1, we analysed genome-wide data from 42 Niedertiefenbach individuals. The community was genetically diverse and carried a large hunter-gatherer ancestry component (~50%) that is most likely due to gene-flow from western hunter-gatherers. We calculated that the admixture processes that gave rise to the Niedertiefenbach population occurred at the end of the Michelsberg Culture or at the beginning of the formation of the Wartberg Culture (3800-3500 BCE), indicating important demographic and cultural transformations at that time in western Europe (unpublished).

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