Ancient Tuberculosis in The Americas: A Midwestern Perspective

该奖项是根据2009年《美国复苏和再投资法案》(公法111-5)提供资金的。我们对引起结核病的细菌物种(结核分枝杆菌复合体，或MTC)的进化以及它们随着时间的推移对我们自己物种的影响的了解极其有限。特别是，MTC在美洲大陆的历史仍然悬而未决。这个项目提出了对来自史前伊利诺伊州约凯姆和斯柴尔德遗址的古代DNA(ADNA)样本的详细分析。这项研究将在伊利诺伊河流域下游的数百名古代个体中检测MTC和其他潜在的骨骼病理(芽生菌病、组织胞浆菌病和布鲁氏菌病)的感染原因，确定MTC感染的时间分布，探索四个MTC基因的遗传变异，以确定存在哪些物种，并阐明现代MTC的进化树。它将完善这些疾病的古病理学诊断，并确定新开发的高通量测序(焦测序)方法是否可以有益地应用于古代病原体的研究。智力价值：这项研究从只有DNA可以提供的角度，解决了关于人类和病原体进化以及美国史前的长期问题。这些分析将在欧洲接触之前确认、描述和更好地了解新大陆人民中结核病感染的性质，并为将新的焦磷酸测序技术应用于这些类型的问题提供概念验证。此外，研究结果将有助于更好地了解这种致残性疾病的演变和流行病学。更广泛的影响：该项目是与印第安纳大学基因组中心使用下一代焦磷酸测序仪器的多用户设施正在进行的努力的一部分，其结果将提供更多的合作研究。这项研究产生的数据将在多个可公开访问的在线数据库中提供。该项目将为两名女研究生和至少一名女本科生提供独特的培训机会，分别构成他们的学位论文和荣誉论文的一部分。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). Our understanding of the evolution of the bacterial species that cause tuberculosis (the Mycobacterium tuberculosis complex, or MTC) and their effect on our own species through time is extremely limited. In particular, the history of MTC on the American continent remains unresolved. This project proposes detailed analyses of ancient DNA (aDNA) samples from the prehistoric Illinois Yokem and Schild sites. This study will detect MTC and other potential infectious causes of skeletal pathology (blastomycosis, histoplasmosis, and brucellosis) in several hundred ancient individuals from the Lower Illinois River Valley, determine the temporal distribution of MTC infection, explore the genetic variation in four MTC genes to identify which species was present and clarify the evolutionary tree of modern MTC. It will refine paleopathological diagnosis of these diseases and determine if newly developed high-throughput sequencing (pyrosequencing) methods can be profitably applied to the study of ancient pathogens. Intellectual Merit: This research addresses long-standing questions about human and pathogen evolution, and American prehistory, from a perspective only aDNA can provide. The analyses will confirm, characterize, and provide better understanding of the nature of tuberculosis infections in peoples in the New World prior to European contact, as well as provide proof-of-concept for the application of new pyrosequencing technology to these types of questions. Additionally, the results will help to better understand the evolution and epidemiology of this crippling disease. Broader Impact: This project is part of an ongoing effort with the Indiana University Genome Center multi-user facility using next-generation pyrosequencing instrumentation, the results of which will provide for additional collaborative research. The data generated from this research will be made available in multiple publicly accessible online databases. The project will provide unique training opportunities for two female graduate students and at least one female undergraduate student, forming a portion of their dissertations and honors thesis, respectively.