Evolutionary history of tuberculosis: An ancient DNA approach

结核病的进化史：古老的 DNA 方法

• 批准号: 0612222
• 负责人: Anne Stone
• 金额: --
• 依托单位: Arizona State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0612222&HistoricalAwards=false
• 关键词: Evolutionary; history; tuberculosis; ancient; DNA

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).

结核病 (TB) 是一种重新出现的传染病，其全球历史在旧世界已有 300 万年以上的历史，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 世纪末欧洲接触之前就对古代美洲人具有致病性。该项目的目标是分析新世界和旧世界结核分枝杆菌古代菌株的 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。具体而言，PI建议对最早的旧世界传播性结核骨骼病例中的菌株进行特征分析，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，考虑新旧世界结核病之前和之后之间的关系继 16 世纪欧洲探索时代之后，评估 17 世纪和 18 世纪欧洲结核病患病率的增加是否是由于新菌株的传播所致。这项研究的科学价值在于，它将通过关注包含表明菌株/谱系隶属关系和关系的信息性核苷酸变化的 DNA 序列来扩展之前的古代 DNA 工作。研究结果将用于验证以下假设：美洲的史前结核病是由与亚洲发现的现代菌株关系最密切的结核分枝杆菌菌株引起的，而新的结核分枝杆菌菌株与今天在亚洲流行的结核分枝杆菌菌株关系最密切。欧洲，在欧洲联系人处介绍。在欧洲样本中，将检验以下假设：17 世纪和 18 世纪欧洲结核病患病率的增加是由于与引入美洲的菌株相同的新菌株所致。从长远来看，该项目旨在建立古代全球菌株模式、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。这项工作将首先关注时间和地理覆盖范围，重点关注疾病通过人类迁徙事件的传播，并描述结核分枝杆菌的进化与人类进化史的关系。该项目更广泛的影响在于，它将为结核分枝杆菌的进化提供独特的视角，并可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。该项目还将涉及研究生和本科生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之外，我们还将在实验室网站上以英语和西班牙语提供有关该项目的信息，供公众访问（http://www.public.asu.edu/~acstone/lab） /molecular_anthropology_lab.htm）。