Objective Recent ancient DNA studies have discovered a basal form of Yersinia pestis, the causative agent of bubonic plague, in 5,000 year-old individuals from Eastern and Central Europe. Even though this strain is an early form that does likely not survive in fleas and might have been less transmissible, the timing intriguingly coincides with a period of substantial societal changes. The archaeological record of 3rd millennium BC Europe clearly demonstrates the demise of terminal Stone Age and the rise of Bronze Age societies across the continent. This turnover has so far been explained by factors such as climatic changes or the advent of new metal working technologies and associated trading networks, which led to a reorganization of past societies. However, contemporaneous genomic data from ancient Europeans have attested major genetic upheavals in Europe 5,000 years ago, with an introgression of 75% genetic ancestry from mobile groups from the eastern steppes appearing in Central Europe. This substantial contribution suggests that early outbreaks of infectious diseases, such as plague, are a vital alternative explanation for large-scale population replacements and thus an attractive hypothesis for investigation. With well-preserved ancient human samples from relevant time periods and key regions in Europe at our disposal, we have a unique and ideal test case to track evolutionary relationships between the human genome and pathogens through time. We will specifically target an extensive number of variants in human immune-related loci using state-of-the-art DNA capture assays alongside deep sequencing of microbial shotgun and pathogen data, which permits a direct characterization of human-pathogen co-evolution. This unique temporal framework will allow us to detect loci under selection in humans and pathogens, and explore the role of infectious diseases and human mobility in past societies via an innovative paleo-epidemiological database and explicit modeling approaches. Fields of science humanitieshistory and archaeologyhistoryprehistorynatural sciencesbiological sciencesgeneticsDNAmedical and health scienceshealth sciencesinfectious diseasesnatural sciencesbiological sciencesevolutionary biologynatural sciencesbiological sciencesgeneticsgenomes Keywords ancient DNA human genome disease migration pathogen selection prehistory Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2017-COG - ERC Consolidator Grant Call for proposal ERC-2017-COG See other projects for this call Funding Scheme ERC-COG - Consolidator Grant Host institution MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Net EU contribution € 1 997 500,00 Address HOFGARTENSTRASSE 8 80539 Munchen Germany See on map Region Bayern Oberbayern München, Kreisfreie Stadt Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 997 500,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Germany Net EU contribution € 1 997 500,00 Address HOFGARTENSTRASSE 8 80539 Munchen See on map Region Bayern Oberbayern München, Kreisfreie Stadt Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 997 500,00