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

他们的愿景是：检测一个古人一生中接触过的所有感染，而不仅仅是那些可能导致他们死亡的感染！传染病可能对人类进化产生了最大的影响，但不可能评估传染病对历史上的人口造成的真正负担。下一代测序技术使鉴定受害者体内某些古代病原体成为可能，古蛋白质组学的应用正在迅速发展；然而，我们无法区分传染病幸存者和从未接触过的人，也无法常规检测最常见的流行疾病和儿童死亡原因（其中许多是病毒，在DNA水平上化学不稳定）。为了理解环境和/或文化习俗的变化如何随着时间的推移影响了我们的易感性，有必要能够直接研究病原体和我们对它们的免疫反应。antientantibodies将通过利用新兴的古蛋白质组学方法、古代DNA、免疫记忆和保存完好、研究充分的流行病背景下的人类骨骼遗骸来提供这种能力，从而前所未有地深入了解传染病的历史。它将制定以下方案：(1)分离、测序和匹配古代病原体抗体；(2)识别骨骼遗骸中重要的古代病毒（例如麻疹、腮腺炎、流感）。由于古蛋白质组学和宏基因组学的最新进展，这两种方法都成为可能。这些新方案将为一个新的研究领域奠定基础：古代免疫组学，并为解决长期以来关于环境、文化和遗传变化对人类免疫系统进化的影响的争论提供方法框架。它将允许研究人员直接评估过去的个人和社区免疫状况。antientantibodies奠定的基础将是未来研究人类过去不可或缺的可转移资源。

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.