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

愿景：检测一个古代个体在他们的生活中接触到的所有感染，而不仅仅是可能杀死他们的东西！传染病可能对人类进化产生了最大的影响，但还不可能评估传染病对历史上的人类人口造成的真正负担。下一代测序使在受害者身上识别某些古老的病原体成为可能，古蛋白质组学的应用正在迅速发展；然而，我们一直无法区分传染病的幸存者和从未接触过的人，也无法例行检测最常见的传播疾病和儿童死亡的原因(其中许多是病毒，在DNA水平上化学不稳定)。要了解环境和/或文化习惯的变化如何随着时间的推移塑造我们的易感性，有必要能够直接研究病原体和我们对它们的免疫反应。通过利用新兴的古蛋白质组学方法、古老的DNA、免疫记忆以及从流行病背景中保存完好、研究得很好的人类骨骼遗骸，古抗体将提供这一能力--使人们能够前所未有地深入了解传染病的历史。它将制定协议，用于(1)分离、测序和匹配病原体的古代抗体，以及(2)在骨骼遗骸中识别重要的古代病毒(例如麻疹、腮腺炎、流感)。这两个都是由于古蛋白质组学和元基因组学最近的进展而成为可能的。这些新的方案将为一个新的研究领域：古代免疫组学奠定基础，并为解决关于环境、文化和遗传变化对人类免疫系统进化的影响的长期争论提供方法论框架。它将允许研究人员直接评估过去个人和社区的免疫状况。古代抗体奠定的基础将是未来人类历史研究不可或缺的、可转让的资源。

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.