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

博士论文研究：追踪传染病的起源：梅毒螺旋体的比较古基因组学研究

• 批准号: 1919662
• 负责人: George Perry
• 金额: $ 3.2万
• 依托单位: Pennsylvania State Univ University Park
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1919662&HistoricalAwards=false
• 关键词: Doctoral; Dissertation; Research; Tracing; origin

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.

梅毒是由梅毒螺旋体亚种引起的性传播感染（STI）。梅毒杆菌。它最近重新成为一场紧迫的全球健康危机。自从 15 世纪末在欧洲突然出现并随后在全球迅速传播以来，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，还是从一直存在于欧洲的一种密螺旋体感染演变而来。 宾夕法尼亚州立大学的研究生王子宇和合作者将采取多方面的方法来调查欧洲过去 500 年来病原体的遗传多样性，以探索解释梅毒起源于欧洲的几种可能性。当前的梅毒螺旋体病原体 - 与几种相关疾病相关 - 可能仅代表最成功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，可以提供有关病原体取得进化成功的过程的线索。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更深入的了解，为预测现代传染性病原体的进化轨迹和人类反应提供了深厚的基础。今天，与过去一样，与性传播感染相关的耻辱在很大程度上干扰了有效干预计划的制定和实施。从历史流行病和公众反应中汲取的经验教训将为培训医疗保健专业人员、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、演变及其在全球范围内的传播，研究小组将对梅毒螺旋体进行测序代表性标本的基因组是从 16 世纪至 19 世纪具有时间和社会特征的欧洲骨骼组合中采样的。由于传统遗传技术（例如聚合酶链式反应）恢复高度降解的古代病原体 DNA 的能力有限，因此古代梅毒螺旋体此前并未得到充分研究。这里将使用灵敏的靶向杂交捕获技术来恢复完整或接近完整的古代梅毒螺旋体基因组。通过将暂时已知的古代病原体基因组与现代病原体基因组进行比较，研究小组可以追踪病原体遗传历史中发生的连续变化。这样做将缩小梅毒起源的可能进化情景，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 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查进行评估，被认为值得支持标准。