Palaeopopulation genomics of Mycobacterium tuberculosis

结核病是一种重新出现的感染，过去在英国也很常见。贫穷、抗药性、艾滋病和移徙是今天发生艾滋病的关键因素。这种疾病通常是由一种名为结核分枝杆菌的细菌引起的，这种细菌以各种菌株的形式存在，具有不同程度的毒力，并在世界不同地区发现。大多数结核病感染发生在肺部，因为它是通过咳嗽传播的，但身体的其他部位也可能被感染，特别是如果这种疾病是通过食用或饮用受感染的食物而感染的。如果不及时治疗，感染会对身体的不同骨骼造成损害，最常见的是脊柱，肋骨，臀部和膝盖。考古学家过去曾利用这些信息来研究结核病，但对骨骼的视觉检查并不能揭示出M。肺结核存在。我们希望能够区分不同的M菌株。考古学上的结核病遗迹，因为这将使我们能够研究疾病的演变。例如，我们可以询问英国不同地区是否存在不同的结核菌株，特别是居住在农村和城镇的人是否暴露于不同类型的结核病。我们还可以研究结核病是如何随着中世纪城市化的发展而演变的。直到最近，还不可能鉴定出M的特定菌株。结核病在骨骼中存在，但现在有技术来研究保存在一些样本中的少量“古代”DNA。在之前的一个项目中，我们使用这些方法对来自英国和欧洲145个考古遗址的491具骨骼进行了研究，这些骨骼中的大多数显示出结核病的迹象，并且可以追溯到罗马时期到公元世纪。大约一半的骨骼似乎不包含任何古代DNA，但我们用足够的样本进行了阳性检测，相信可以在不同地点和时期的结核菌株之间进行有意义的比较。在拟议的项目中，我们将使用新的方法对古代DNA进行测序，以获得我们所需的详细信息，以便比较M的考古品种。结核病与现代菌株的细菌。我们已经证明了这些方法是有效的，因为我们已经成功地用它们研究了一具来自英国利兹的世纪的青少年女性骨骼。我们发现这个人感染了一种结核病，这种结核病在今天很少见，但我们认为在过去更常见。在新项目中，我们打算对24具骨架使用相同的方法，其中22具来自英国，1具来自法国，1具来自乌克兰。我们希望能够在这些其他骨骼中获得同样详细的结核菌株信息，从而表明古代DNA测序作为研究结核病进化的一种手段具有真正的潜力。

Tuberculosis is a reemerging infection that was also common in the past in Britain. Poverty, drug resistance, AIDS and migration are key factors in its occurrence today. The disease is usually caused by the bacterium called Mycobacterium tuberculosis, which exists as a variety of strains that have different degrees of virulence and are found in different parts of the world. Most tuberculosis infections occur in the lungs, because it is transmitted via coughing, but other parts of the body can also be infected, especially if the disease is caught by eating or drinking infected foods. If left untreated the infection can cause damage to different bones in the body, most commonly the spine, ribs, hips and knees. Archaeologists have used this information to study tuberculosis in the past, but visual examination of skeletons does not reveal which of the various strains of M. tuberculosis is present. We would like to be able to distinguish different strains of M. tuberculosis in archaeological remains because this would enable us to study the evolution of the disease. We could, for example, ask if different strains of tuberculosis were present in different parts of Britain, and in particular if people living in the countryside and in towns were exposed to different types of tuberculosis. We could also examine how tuberculosis evolved in response to the increased urbanization that occurred during the Mediaeval period. Until recently it was impossible to identify the particular strain of M. tuberculosis present in a skeleton, but now there are techniques for studying the small amounts of 'ancient' DNA that are preserved in some samples. In a previous project we used these methods with 491 skeletons from 145 archaeological sites from across all of Britain and Europe, most of these skeletons showing signs of tuberculosis, and dating from the Roman period to the 19th century AD. About half of the skeletons did not appear to contain any ancient DNA, but we achieved positive detections with enough samples to believe that meaningful comparisons can be made between tuberculosis strains from different places and periods. In the proposed project we will use new methods for sequencing ancient DNA in order to obtain the detailed information we need in order to compare an archaeological variety of M. tuberculosis with modern strains of the bacterium. We have already shown that these methods work, because we have used them successfully with one skeleton, of an adolescent female from 19th century Leeds, England. We showed that this person had been infected with a strain of tuberculosis that is rare today, but which we think was much more common in the past. In the new project we intend using the same approach with 24 skeletons, 22 from Britain, one from France and one from the Ukraine. We hope to be able to obtain equally detailed information on the strains of tuberculosis in these other skeletons, and hence to show that ancient DNA sequencing has genuine potential as a means of studying the evolution of tuberculosis.