Palaeopopulation genomics of Mycobacterium tuberculosis

Lead Research Organisation: University of Manchester
Department Name: School of Medical Sciences


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.

Planned Impact

The bioarchaeologists, anthropologists and historians with whom we wish to engage include academic researchers for whom the normal channels for dissemination of project results will be appropriate. We will ensure that we publish our results in journals that are read by the academic archaeological community and we will present our results at the UK Archaeological Sciences 2015 and Paleopathology Association 2016 meetings, which are attended by this community. These beneficiaries also include contract archaeologists and museum curators, in particular ones who have allowed us to sample the skeletons that we will study in this project. This subcommunity is disparate and no single general dissemination process is suitable for all members. We will publish summaries of our results in the Museums Journal and The Historic Environment Journal, which are targeted at these beneficiaries. We will also follow the strategy that proved successful during our previous project NE/E018564/1 and communicate the interim and final outcomes of the project directly by email or letter. We will also include these beneficiaries as authors on publications arising from the project, as appropriate. The clinical microbiology, medical geography and evolution medicine communities are principally academic researchers with whom we will engage by publishing results of interest to the beneficiaries in appropriate journals, and by presentation of results at appropriate conferences. The latter is an ongoing activity by the PI and CoI, both of whom contributed to, for example, the 2012 TB Evolution Meeting at Szeged. With regards to the general public, we will take advantage of all those opportunities that arise within our universities and elsewhere to participate in public engagement especially with schoolchildren. In addition, we will create pages relating to the project in the Children's University of Manchester, we will write an article on the project in the Manchester Faculty of Life Sciences schools magazine 'Biological Sciences Review', we will organise a workshop on crops and DNA for schoolchildren as part of Manchester Science Week in 2014 and Durham Celebrate Science Week in 2015, and the PI will include the project in the series of lectures on DNA and human history that he gives to his local community education group the Glossop Guild. Measures of success will be the number of hits for the Children's University of Manchester pages, and the number of schoolchildren attending the Manchester and Durham Science Week workshops plus their feedback. Genuine success in engaging with clinical microbiologists cannot be measured within the lifetime of the project but will be evident from the future use that these end users make of the outcomes of the research.


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Description The aim of this project was to obtain DNA sequences from the preserved 'ancient' DNA of prehistoric Mycobacterium tuberculosis present in archaeological skeletons of people who were suffering from tuberculosis when they died. By comparing these sequences with those from extant Mycobacterium tuberculosis strains we planned to study the evolution of tuberculosis in the past, for example the impact of urbanisation during the mediaeval period on the spread and characteristics of the disease. We met the technical objectives of the project by preparing a variety of DNA sequencing libraries, using different approaches, from a set of skeletons showing osteological signs of tuberculosis and dating back to the Roman period. We discovered that the preservation of DNA in these skeletons is variable and that in the majority of cases there is insufficient DNA for comprehensive genetic analysis. We also discovered that the problems caused by contamination of the skeletons with environmental, non-pathogenic bacteria related to Mycobacterium tuberculosis is greater than previously thought, and that it is difficult to distinguish genuine TB DNA from the DNA of these contaminating bacteria. Despite these problems we obtained an accurate and complete genome sequence for one skeleton, of a young female from a 19th century site in Leeds, UK, and showed that this strain of TB was related to other strains believed to be common in 19th century Europe. We also obtained partial data from various other skeletons which enabled us to compare the evolution of Mycobacterium tuberculosis over the last 2000 years with schemes derived from studies of extant strains, showing that those schemes are largely correct.
Exploitation Route Our demonstration of the problems arising from contamination of skeletons by environmental mycobacteria is influencing the approaches that other groups are using in analysing TB DNA sequence data from archaeological remains, and is forcing a reassessment of the accuracy of some of the published literature. We do not intend to take this project forward ourselves, beyond publication of two or three additional papers reporting the data we have obtained, but we are collaborating with a group at the Max Planck Institute, Jena, Germany, who are attempting DNA analyses with some of the samples that we collected as part of the previous NERC grant that we held for this research programme.
Sectors Environment,Culture, Heritage, Museums and Collections

Description Presentations for schoolchildren were given at the Manchester Institute of Biotechnology Open Days in November 2014, November 2015 and November 2016. Presentations for the general public were given at the Glossop Guild in March 2015 and Longdendale Archaeology Society in February 2015.
First Year Of Impact 2014
Sector Culture, Heritage, Museums and Collections
Impact Types Cultural