York scientists contribute to ‘breakthrough’ in tropical disease research
Posted on 29 June 2007
Professor Deborah Smith led the York team that contributed to the project, at the Wellcome Trust Sanger Institute, which compared the genomes of three Leishmania species and identified a small number of genes, many new to biology, which will provide a framework to target the search for new therapies.
In their report in Nature Genetics, 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 will provide new insights into those processes that may determine disease severity in humans.
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, the Plasmodium species that cause different types of malaria vary by about 20% of their total gene content.
Professor Smith, of the Immunology and Infection Unit - a joint venture between the Department of Biology at the University of York and the Hull York Medical School - said: "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."
"Perhaps only a few parasite genes are important in determining which type of disease develops after infection and the human genome plays a major role in clinical outcome."
The results picked up another surprising finding: the team could assign a function to only one-third of the 200 genes restricted to one or two of the species.
"The genome sequences have given us a short-cut to a small number of largely novel genes," explained Dr Chris Peacock, first author on the report. "Given their lack of similarity to human genes, they present a limited repertoire of potential targets for drug and vaccine development allowing researchers to optimise the use of limited resources."
Around 350 million people in 88 countries on four continents are at risk of Leishmaniasis and its incidence has risen sharply over the past ten years. It is transmitted by the bite of various species of sandfly: wild and domesticated animals - as well as humans - act as a reservoir for the disease. Leishmaniasis is one of the neglected diseases that desperately needs new research to identify new therapeutics: treatment for fatal visceral disease currently depends on expensive first-line drugs of varying toxicity and there is no effective vaccine. The affordable drugs have been in use for more than half a century and drug resistance is rife, creating a desperate need for alternative measures. A recent World Health Organisation resolution recommends setting up a global task force to determine priorities and frame an effective policy for leishmaniasis control.
Peacock C. et al. 2007. Comparative genomic analysis of three Leishmania species that cause diverse human disease. Nature Genetics 39, 839-847.
ENDS