Doctoral Dissertation Improvement: The Origin of Syphilis and the Evolution of the Treponema Pallidum Subspecies: A Phylogenetic Approach

博士论文改进：梅毒的起源和梅毒螺旋体亚种的进化：系统发育方法

• 批准号: 0622399
• 负责人: George Armelagos
• 金额: $ 1.19万
• 依托单位: Emory University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2008-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0622399&HistoricalAwards=false
• 关键词: Doctoral; Dissertation; Improvement; Origin; Syphilis

Controversy has surrounded the origin of syphilis since the 15th century. Some have speculated that syphilis arose from a pathogen acquired in the New World by Columbus and his men. Alternative hypotheses are that 1) syphilis was always present in Europe but was previously confused with other diseases such as leprosy; and 2) syphilis arrived in Europe during the Renaissance but originated in Africa and not the New World. A review of the geographical span of the treponematoses over time, as revealed in the paleopathological record, has demonstrated that evidence of treponemal disease is abundant in the Pre-Columbian New World and seemingly absent from European and North African sites. However, isolated reports of treponemal disease in these areas before the 1490s have kept the debate alive. In addition, the relationship between Treponema pallidum subsp. pallidum, the bacterium that causes syphilis, and the other T. pallidum subspecies that cause the similar but non-venereal diseases yaws, endemic syphilis, and pinta continues to puzzle biologists. Although the diseases are characterized by strikingly different symptoms, morphological and genetic differences which can be used to distinguish the pathogens have remained elusive. This project seeks to elucidate the evolutionary trajectory of the subspecies using phylogeography.Samples have been gathered from cases of syphilis, yaws, and endemic syphilis all over the world. They represent the largest collection of non-venereally transmitted T. pallidum DNA available in a lab collection today. Using targeted genetic analysis, variable sites within and between the subspecies will be identified. Phylogenetic analyses will then be performed upon these differences in order to test various hypotheses regarding the origin of syphilis and the relationship of the T. pallidum subspecies to one another.This project addresses two long-standing problems in the history of disease while simultaneously studying mechanisms of pathogen evolution in response to human-imposed selective pressures. Because information from phylogenetic methods will join copious paleopathological data on T. pallidum infection in past populations, the proposed research provides a unique opportunity to link adaptive events in a pathogen to changes in epidemiology and disease manifestations as well as host social and sexual practices. This type of knowledge will be applicable to other human pathogens, such as HIV. Evolutionary changes in transmission, resulting in either a novel mode of infection or greater efficiency in an existing mode, have played important roles in past epidemics and are a major public health concern. This study may elucidate the conditions surrounding and mechanisms underlying such changes and could thus help to inform interventions. In addition, the data produced from comparative genetic analysis may help make sense of puzzling paleopathological findings and dispel the mystery surrounding the origin of syphilis by providing novel objective data. Finally, this study will result in the training of a PhD student.

自 15 世纪以来，围绕梅毒的起源一直存在争议。一些人推测梅毒是由哥伦布和他的手下在新大陆获得的病原体引起的。另一种假设是：1）梅毒一直存在于欧洲，但之前曾与麻风病等其他疾病混淆； 2）梅毒在文艺复兴时期传入欧洲，但起源于非洲而不是新大陆。正如古病理学记录所揭示的那样，对密螺旋体病随时间的地理跨度进行的回顾表明，在前哥伦布时代的新世界中存在丰富的密螺旋体疾病的证据，而在欧洲和北非地区似乎不存在。然而，1490 年代之前这些地区关于密螺旋体疾病的零星报道使争论继续存在。此外，梅毒螺旋体亚种之间的关系。梅毒螺旋体（引起梅毒的细菌）和其他梅毒螺旋体亚种（引起类似但非性病的雅司病、地方性梅毒和品塔病）继续困扰着生物学家。尽管这些疾病的症状明显不同，但可用于区分病原体的形态和遗传差异仍然难以捉摸。该项目旨在利用系统发育地理学阐明该亚种的进化轨迹。样本是从世界各地的梅毒、雅司病和地方性梅毒病例中收集的。它们代表了当今实验室收集的最大的非性传播梅毒螺旋体 DNA 集合。使用有针对性的遗传分析，将识别亚种内部和亚种之间的可变位点。然后将对这些差异进行系统发育分析，以测试有关梅毒起源和梅毒螺旋体亚种之间关系的各种假设。该项目解决了疾病史上两个长期存在的问题，同时研究病原体进化机制以应对人类施加的选择压力。由于来自系统发育方法的信息将与过去人群中梅毒螺旋体感染的大量古病理学数据相结合，因此拟议的研究提供了一个独特的机会，将病原体的适应性事件与流行病学和疾病表现以及宿主社会和性行为的变化联系起来。此类知识将适用于其他人类病原体，例如艾滋病毒。传播方式的进化变化，导致新的感染模式或现有模式的更高效率，在过去的流行病中发挥了重要作用，也是一个主要的公共卫生问题。这项研究可能会阐明这些变化的周围条件和机制，从而有助于为干预措施提供信息。此外，比较遗传分析产生的数据可能有助于理解令人费解的古病理学发现，并通过提供新颖的客观数据来消除围绕梅毒起源的谜团。最后，这项研究将培养一名博士生。