A comparison of three parasite species that cause Leishmaniasis has identified a small number of genes, many new to biology, that will provide a framework to target the search for new treatments. Leishmaniasis is a devastating disease that affects about two million people each year and threatens one-fifth of the world's population and new treatments are desperately needed.
In their report in Nature Genetics, published online on Sunday 17 June 2007, the researchers compared the genomes of L. infantum and L. braziliensis, which cause life-threatening visceral and disfiguring mucocutaneous leishmaniasis, respectively, with the sequence they produced in 2005 for L. major, which causes a less severe, cutaneous form of the disease. Despite the major differences in disease type, only 200 out of more than 8000 genes present in each genome were found to be differentially distributed between the three species. This exceptionally small variation in gene content has given new insights into those processes that may determine disease severity in humans.
"Identifying factors that allow three closely related organisms to cause vastly different clinical outcomes is a major quest for researchers and in this study we have narrowed the search to a number that can be realistically studied," commented Dr Matt Berriman, senior author on the paper, from the Wellcome Trust Sanger Institute.
The researchers found only five genes in the L. major genome for which no trace could be found in the other two species. By contrast, in Plasmodium, which causes malaria, about 20% of genes differ between related species.
"Clearly there must have been considerable evolutionary pressure over time to maintain the structure and sequence of the Leishmania genomes - the degree of similarity between these species was unexpected," explained Professor Deborah Smith, collaborator on this project at the University of York. "Perhaps only a few parasite genes are importan
Contact: Don Powell
Wellcome Trust Sanger Institute