Doctoral Dissertation Research: Tracing the origin of infectious disease: A comparative paleogenomics study of Treponema pallidum

梅毒是一种由梅毒螺旋体引起的性传播感染。螺旋体细菌。它最近重新成为一场紧急的全球卫生危机。自15世纪末在欧洲突然出现并随后迅速在全球传播以来，这种疾病的起源一直是个谜。长期以来，人们一直在争论梅毒是从美洲传入欧洲，还是从欧洲一直存在的一种螺旋体感染演变而来。宾夕法尼亚州立大学的研究生Ziyu Wang和合作者将采取多方面的方法来调查过去500年来欧洲病原体的遗传多样性，以探索梅毒在欧洲起源的几种可能性。目前的苍白球绦虫病原体——与几种相关疾病相关——可能只代表了最成功的或最近出现的遗传变异。从人类学的角度来看，在人类社会文化系统的背景下考虑古代基因组，可以为病原体取得进化成功的过程提供线索。最终，对导致人类与其病原体之间复杂和动态相互作用的因素有了更深入的了解，为预测现代感染性病原体和人类反应的进化轨迹提供了深入的时间基础。今天，与过去一样，性传播感染相关的污名在很大程度上妨碍了有效干预方案的制定和实施。从历史流行病和公众应对中吸取的经验教训将为培训卫生保健专业人员、性传播感染高危人群和公众提供宝贵的工具。为了弄清梅毒的起源、演变及其在世界范围内的传播，研究小组将对从16至19世纪具有时间和社会特征的欧洲骨骼组合中取样的代表性标本进行梅毒T. pallidum基因组测序。由于传统的遗传技术（如聚合酶链反应）恢复高度降解的古代病原体DNA的能力有限，古代苍白锥菌以前没有得到很好的研究。在这里，一种敏感的靶向杂交捕获技术将用于恢复完整或接近完整的古代苍白球绦虫基因组。通过比较暂时已知的古代病原体基因组与现代病原体基因组，研究小组可以追踪病原体遗传史上发生的顺序变化。这样做将缩小梅毒起源的可能进化场景，并指出导致梅毒的病原体变异首次出现的时间。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Syphilis is a sexually transmitted infection (STI) caused by Treponema pallidum subp. pallidum bacteria. It has recently reemerged as an urgent worldwide health crisis. The origin of the disease has been a mystery since its sudden appearance in Europe at the end of the 15th century and its subsequent rapid global spread. It has long been debated whether syphilis was introduced to Europe, perhaps from the Americas, or evolved from a form of treponemal infection that had been in Europe all along. Graduate student Ziyu Wang and collaborators at The Pennsylvania State University will take a multi-faceted approach to investigate the pathogen's genetic diversity over the past 500 years in Europe to explore several possibilities to explain syphilis' origin in Europe. The current T. pallidum pathogens - associated with several related diseases - likely represent only the most successful or recently emerged genetic variants. Examined through an anthropological lens, ancient genomes when considered within the context of human sociocultural systems yield clues about the processes through which pathogens have achieved their evolutionary success. Ultimately a more informed understanding of the factors that contribute to the complex and dynamic interactions between humans and their pathogens provides a deep-time foundation for predicting the evolutionary trajectories of modern infectious pathogens and human responses. Today, as in the past, STI-related stigma has done much to interfere with the development and implementation of effective intervention programs. Lessons learned from historic epidemics and the public response will provide valuable tools for training healthcare professionals, STI high-risk groups, and the public.To untangle syphilis' origin, its evolution, and its worldwide spread, the research team will sequence T. pallidum genomes from representative specimens sampled from temporally and socially well-characterized European skeletal assemblages dating to the 16th to 19th centuries. Ancient T. pallidum has previously not been well studied because of the limited ability of conventional genetic techniques (e.g., polymerase chain reaction) to recover highly-degraded ancient pathogen DNA. Here a sensitive targeted hybridization capture technique will be used to recover complete, or near-complete, ancient T. pallidum genomes. By comparing temporally known ancient pathogen genomes with their modern equivalents, the research team can track the sequential changes that occurred in the pathogen's genetic history. Doing so will narrow the possible evolutionary scenarios for the origin of syphilis and point to when the pathogen variant that causes syphilis first emerged.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.