The genome of the blood fluke Schistosoma mansoni

Abstract

Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. Here we present analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and new families of micro-exon genes that undergo frequent alternative splicing. As the first sequenced flatworm, and a representative of the Lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, and the identification of membrane receptors, ion channels and more than 300 proteases provide new insights into the biology of the life cycle and new targets. Bioinformatics approaches have identified metabolic chokepoints, and a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease. Two international consortia this week report the whole genome sequences of the blood flukes Schistosoma mansoni and Schistosoma japonicum, two of the three major pathogens that cause schistosomiasis, also called bilharzia. Schistosomiasis is a 'neglected' tropical disease affecting more than 200 million people in 76 countries. Analyses of the new genome sequences provide insights into the molecular architecture and host interactions of these pathogens, as well as avenues for future development of targeted interventions for this disease. These are the first two flatworm genomes to be sequenced, so they offer new angles on the early events in animal evolution, in particular the determination of body pattern and the development of tissues into organs. Schistosoma mansoni and Schistosoma japonicum are the pathogenic agents that cause the tropical disease schistosomiasis. Here, and in an accompanying paper, the genomes of these two flatworms are sequenced and analysed. The results provide insights into the molecular architecture and host interactions of the flatworms, as well as avenues for future development of targeted interventions for schistosomiasis.