Leprosy genome shows massive gene decay
There are nearly 700,000 new cases of leprosy each year. However, doctors don't fully understand how leprosy spreads and cannot grow it in the laboratory. New research published today in Nature magazine reveals that the organism that causes leprosy may have manoeuvred itself into an evolutionary cul-de-sac.
To understand and, ultimately, to attack this disease, researchers at the Wellcome Trust Sanger Centre near Cambridge and the Institut Pasteur in Paris have sequenced and analysed the genome of the leprosy-causing bacterium, Mycobacterium leprae. They also compared the sequence with that of the closely related organism that causes TB (M. tuberculosis). The sequence of M. leprae and the comparison produce some startling findings:
- The leprosy genome has only 1600 genes - TB has about 4000
- Remarkably, 90% of leprosy's reduced gene set is shared with TB
- Only 50% of the genome of leprosy codes for proteins - in TB, as in most bacteria, it is over 90%
- More than one quarter of the leprosy genome is pseudogenes - genes that have decayed and become inactive: one-fifth of the genome is probably remnants of genes
- A family of 170 genes in TB thought to interact with host defences is reduced to only 9 genes in leprosy
- Leprosy has preserved many of the core functions necessary for bacterial life, but has lost most of the diverse mechanisms found in TB for energy production and nutrient uptake, which probably explains the exceptionally slow growth.
The outcome is that a drastically streamlined genome may mean that M. leprae has discarded so many genes that it can survive only by infecting humans. The reduced gene set may also account for its very slow growth in humans and its inability to grow in culture.
Leprosy is most prevalent in Asia, Africa and Latin America: there are about 1.2 million cases. Often the disease will regress, but only after a prolonged period of infection and damage.
The leprosy bacterium attacks the insulation (the myelin sheath, which is analogous to plastic coating of cables) around nerves. The affected regions become insensitive and easily damaged or disfigured.
"This is an exciting new path to tackling this disease. Diagnosis and treatment of leprosy are currently very difficult: with this new genome information we will be able to develop new and specific diagnostic tests and have already identified new potential targets to attack the leprosy bacterium."
Project Director, Professor Stewart Cole of the Institut Pasteur
"The leprosy genome is a fascinating snapshot of evolution in action. We can see how it has lost so many genes, those it has preserved - most often the core activities - and those that distinguish it from its cousin, the TB bacterium. The analysis shows the power of comparative genomics (looking at DNA from two organisms), one of the strengths of the programmes at the Sanger Centre."
Dr Julian Parkhill, Project Manager at the Sanger Centre
As with all projects at the Sanger Centre, the DNA sequence information is released onto the internet without restriction or charge to users. The project was funded by the Heiser Trust (Heiser Program for Research in Leprosy and Tuberculosis of The New York Community Trust), L'Association Francaise Raoul Follereau, ILEP (which includes LEPRA in the UK), The Institut Pasteur and The Wellcome Trust.