Evolutionary history of tuberculosis: An ancient DNA approach

结核病（TB）是一种重新出现的传染病，在旧世界有超过300万年的全球历史，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--早在世纪晚期欧洲人接触结核分枝杆菌之前，结核分枝杆菌就对古代美洲人具有致病性。该项目的目标是分析来自古老的M菌株的DNA。新世界和旧世界的结核病，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。具体而言，PI建议表征来自最早的旧世界播散性结核病骨骼病例的菌株，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的关系，考虑16世纪欧洲探险时代之前和之后旧世界和新世界结核病之间的关系，并评估17和18世纪欧洲结核病流行率的增加是否是由于新菌株的传播。这项研究的科学价值在于，通过关注含有指示菌株/谱系隶属关系和关系的信息核苷酸变化的DNA序列，将扩展以前的古代DNA工作。研究结果将用于解决美洲史前结核病是由M.结核菌株，最密切相关的现代菌株在亚洲发现和新菌株的M。结核病，最密切相关的那些今天在欧洲流行，是在欧洲接触介绍。在欧洲样本中，将检验以下假设：17和18世纪欧洲结核病流行率的增加是由于与引入美洲的菌株相同的新菌株。从长远来看，该项目旨在建立古老的全球菌株模式，疾病史，毒力模式以及与其他分枝杆菌如M。leprae和M.牛这项工作将首先集中在时间和地理范围，集中在疾病的传播，通过人类迁移事件和特点的M。结核病与人类进化史的关系这个项目的更广泛的影响是，它将提供一个独特的观点到M的演变。它可以为寻求了解生物体生物学和开发新疫苗策略的研究人员提供有价值的见解。该项目还将涉及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成果外，我们还将在实验室网站（http：//www.public.asu.edu/lab/molecular_anthropology_lab.htm）上以英文和西班牙文提供有关该项目的信息，供公众查阅。

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).