Evolutionary history of tuberculosis: An ancient DNA approach

结核病（TB）是一种重新出现的传染病，在旧大陆有300多万年的全球历史，起源于非洲。最近的分子遗传学研究证实了古病理学家长期以来的怀疑——结核分枝杆菌早在15世纪晚期与欧洲人接触之前就已经是古代美洲人的致病菌了。该项目的目标是分析来自新世界和旧世界的古代结核分枝杆菌菌株的DNA，以了解它们与现代菌株的关系，从而解决有关结核病进化史的问题。具体来说，这些项目建议对来自旧大陆最早的弥散性结核病骨骼病例的菌株进行表征，探索这些早期菌株与铁器时代/罗马时代在英国发现的菌株之间的关系，考虑16世纪欧洲大探险时代前后新旧世界结核病之间的关系，并评估17世纪和18世纪欧洲结核病患病率的增加是否由于新菌株的传播。这项研究的科学价值在于，它将扩展以前的古代DNA工作，将重点放在含有信息丰富的核苷酸变化的DNA序列上，这些变化表明菌株/谱系的隶属关系和关系。这些结果将用于解决以下假设：美洲史前结核病是由与亚洲发现的现代结核分枝杆菌菌株最密切相关的结核分枝杆菌菌株引起的，而与今天在欧洲流行的结核分枝杆菌菌株最密切相关的新结核分枝杆菌菌株是通过与欧洲人接触而传入的。在欧洲的样本中，关于17和18世纪欧洲结核病流行率上升是由于与引入美洲的新菌株相同的新菌株的假设将得到检验。从长远来看，该项目旨在建立古老的全球菌株模式、疾病历史、毒力模式以及与其他分枝杆菌（如麻风分枝杆菌和牛分枝杆菌）的关系。这项工作将首先侧重于时间和地理覆盖范围，集中在通过人类迁移事件传播的疾病上，并描述结核分枝杆菌与人类进化史的关系。这个项目的更广泛的影响是，它将为结核分枝杆菌的进化提供一个独特的视角，并可能为寻求了解这种有机体的生物学和开发新的疫苗策略的研究人员提供有价值的见解。该项目还包括对研究生和本科生进行实验室方法和分析方面的培训。最后，除了在学术文章中传播结果外，我们还将在实验室网站（http://www.public.asu.edu/~acstone/lab/molecular_anthropology_lab.htm）上以英语和西班牙语向公众提供有关该项目的信息。

Tuberculosis (TB) is a re-emerging infectious disease with a global history extending over 3 million years in the Old World and originating in Africa. Recent research in molecular genetics confirms what paleopathologists have long suspected - that Mycobacterium tuberculosis was pathogenic for ancient Americans long before late 15th century European contact. The goal of this project is to analyze DNA from ancient strains of M. tuberculosis in both the New World and Old World to understand their relationship to modern strains, thus addressing questions about the evolutionary history of TB. Specifically, the PIs propose to characterize strains from the earliest Old World skeletal cases of disseminated TB, explore the relationship of these early strains to those found in Britain by Iron Age/Roman times, consider the relationship between Old and New World TB prior to and following the 16th century era of European Exploration, and assess whether the increase in prevalence of tuberculosis during the 17th and 18th centuries in Europe was due to the spread of new strains. The scientific merit of this study is that will expand previous ancient DNA work by focusing on DNA sequences containing informative nucleotide changes that indicate strain/lineage affiliations and relationships. The results will be used to address the hypotheses that prehistoric TB in the Americas was caused by M. tuberculosis strains that are most closely related to modern strains found in Asia and that new strains of M. tuberculosis, most closely related to those prevalent today in Europe, were introduced at European contact. In European samples, the hypothesis that the increase in prevalence of tuberculosis in Europe during the 17th and 18th centuries was due to new strains that were the same as those introduced into the Americas will be tested. In the long term, this project is designed to establish ancient global strain patterning, history of the disease, pattern of virulence, and relationships with other mycobacteria such as M. leprae and M. bovis. This work will focus first upon temporal and geographic coverage, centering upon the spread of the disease through human migration events and characterizing the evolution of M. tuberculosis in relationship to human evolutionary history. The broader impact of this project is that it will provide a unique viewpoint into the evolution of M. tuberculosis and could provide insights valuable to researchers seeking an understanding of the biology of the organism and developing new vaccine strategies. This project will also involve graduate and undergraduate student training in laboratory methods and analyses. Finally, in addition to disseminating results in scholarly articles, we will include information about the project that is accessible to the general public in English and Spanish on the laboratory website (http://www.public.asu.edu/~acstone/lab/molecular_anthropology_lab.htm).