1st March 2002

The complete genome of Mycobacterium bovis has been sequenced

A step forward in the fight against bovine tuberculosis: The complete genome of Mycobacterium bovis has been sequenced

The sequence of the entire genome of the organism that causes bovine tuberculosis has been determined in a collaborative project between Glyn Hewinson's team at the Veterinary Laboratories Agency (UK), Stewart Cole's team at the Institut Pasteur (France), and the Pathogen Genome Sequencing Unit at the Sanger Institute (UK), directed by Bart Barrell.

Dr Glyn Hewinson, leader of the project at VLA commented "This is a great day for research into bovine tuberculosis. Our challenge now is to use this wealth of information as a springboard to develop the tools that are so desperately needed to eradicate this devastating disease which results in global economic losses of over $3 billion each year".

Mycobacterium bovis is the causative agent of tuberculosis in a wide range of wild and domesticated animals. The Office International des Epizooties (OIE) reports that M. bovis is rapidly emerging as one of the most significant infectious diseases of wildlife in many parts of the world. TB has achieved the dubious distinction of overtaking man as the main threat to the survival of the black and white rhinoceros. It is spreading rapidly through the game reserves of southern Africa where it affects a wide range of species including buffalo, lions, cheetah and baboons. It is a worldwide problem that affects natural populations, domesticated breeds and industry.

The bacillus is also capable of causing disease in humans and was the cause of approximately 6% of total human deaths due to tuberculosis in Great Britain in the 1930s and 1940s. Humans were exposed, in particular, through the consumption of contaminated dairy products but the introduction of pasteurization of milk in the 1930s dramatically reduced the transmission from cattle to man. Human tuberculosis caused by M. bovis is still a health issue in many developing countries.

The genome-sequencing project began in 1999 as a result of the rapidly growing number of TB cases in cattle in Great Britain. The project was funded by the Ministry of Agriculture, Fisheries and Food, GB (now DEFRA), Institut Pasteur and the Wellcome Trust. The aim is to use the genomic information generated by this project to accelerate the development of new tools such as improved diagnostic tests to control bovine tuberculosis. The genome sequence will also allow a detailed analysis of the disease-causing mechanisms of M. bovis, offering the hope of developing new vaccines against the disease.

The sequencing project has revealed that the genome of M. bovis is greater than 99.9% identical to Mycobacterium tuberculosis, the causative agent of human tuberculosis, which kills over two million people a year. Analysis of the two genomes has revealed an unexpected evolutionary scenario for the development of these two pathogens. In the past it was believed that the human tubercle bacillus, Mycobacterium tuberculosis, was derived from M. bovis due to the bovine bacillus crossing the species barrier into man at the time of the domestication of cattle 10,000 to 15,000 years ago. However, the genome sequence of M. bovis has revealed that this is unlikely to be the case. Since the M. bovis genome is smaller than that of M. tuberculosis, it is more likely that man gave tuberculosis to cattle or that the two organisms evolved separately from a common ancestor. This work on the post-genomic applications of the genome sequence, which is to be reported in the latest edition of the Proceedings of the National Academy of Sciences, USA, calls for a rethink on our previous understanding of the dynamics between human and animal disease.

Introducing a seminar held at VLA Weybridge today (1 March), Professor Steve Edwards, Chief Executive of VLA, said "I am proud that our Institute has been a partner in such an important project. The completion of the M.bovis genome sequence now paves the way for the development of a new generation of tools to control bovine tuberculosis."

Pathogens and M. bovis Information

The Wellcome Trust Sanger Institute, which receives the majority of its funding from the Wellcome Trust, is one of the world's leading genome sequencing centres. Both the Sanger Institute and the Wellcome Trust have been at the forefront of efforts to keep sequence data in the public domain. The Institute employs nearly 600 people in the purpose-built campus at Hinxton, near Cambridge, UK. The Institute is a leading partner in the Human Genome Project, and is responsible for sequencing one-third of the human genome sequence. A major focus of the Institute's work is in national and international projects to sequence the genomes of disease-causing organisms.

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