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引起的性传播感染（STI）。苍白球细菌它最近再次成为一个紧迫的全球健康危机。自15世纪世纪末在欧洲突然出现并随后在全球迅速蔓延以来，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否是从美洲传入欧洲的，或者是从沿着存在于欧洲的一种密螺旋体感染演变而来的。 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。目前的T。苍白球病原体-与几种相关疾病有关-可能只代表最成功的或最近出现的遗传变异。从人类学的透镜来看，如果把古代基因组放在人类社会文化系统的背景下考虑，就会发现病原体在进化过程中取得成功的线索。最终，对导致人类与病原体之间复杂和动态相互作用的因素的更明智的理解为预测现代传染性病原体和人类反应的进化轨迹提供了深刻的时间基础。今天，与过去一样，与性传播感染有关的耻辱感在很大程度上干扰了有效干预方案的制定和实施。从历史上的流行病和公众反应中吸取的教训将为培训医疗保健专业人员、STI高危人群和公众提供有价值的工具。pallidum基因组从代表性标本采样时间和社会特征良好的欧洲骨骼组合可追溯到16日至19世纪。古T由于常规遗传技术的能力有限（例如，聚合酶链反应）来回收高度降解的古老病原体DNA。在这里，一种灵敏的靶向杂交捕获技术将被用来恢复完整的，或接近完整的，古老的T。苍白球基因组通过将时间上已知的古代病原体基因组与现代病原体基因组进行比较，研究小组可以跟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体首次出现的时间。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。