Identifying pathogen exposure via immunological memory in ancient populations using proteins and DNA

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The vision: detecting all the infections an ancient individual was exposed to in their life, not just what might have killed them! Infectious disease has likely had the greatest impact on human evolution, yet it has not been possible to assess the true burden of communicable disease on historic human populations. Next Generation Sequencing has made it possible to identify certain ancient pathogens in victims and the applications of paleoproteomics are rapidly developing; however, we have been unable to distinguish between survivors of communicable disease and those who were never exposed, nor routinely detect the most common circulating illnesses and causes of child mortality (many of which are viruses, chemically unstable at the DNA level). To understand how shifts in environment and/or cultural practices have shaped our susceptibility through time, it is necessary to be able to directly study both pathogens and our immune response to them. AncientAntibodies will provide this ability by exploiting emerging paleoproteomics methods, ancient DNA, immunological memory and well-preserved, well-studied human skeletal remains from epidemic contexts- allowing unprecedented insight into the history of infectious disease. It will develop protocols for (1) isolating, sequencing and matching ancient antibodies to pathogens and (2) identifying important, ancient viruses (e.g. measles, mumps, influenza) in skeletal remains. Both are made possible by recent advances in paleoproteomics and metagenomics. These novel protocols will build the foundation for a new field of study: Ancient Immunomics and provide the methodological framework for settling long-standing debates regarding the impact of environmental, cultural and genetic shifts on the evolution of the human immune system. It will allow researchers to directly assess past individual and community immune status. The groundwork laid by AncientAntibodies will be an indispensable, transferable resource for future studies of the human past.