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.

Figure 1. Physical map of Schistosoma mansoni

Idiogram of S. mansoni chromosomes W, Z (a) and 3 (b). S. mansoni BAC clones were mapped to the karyotype of S. mansoni by FISH. The solid black areas are heterochromatin and the open areas are euchromatin. The BAC clones are identified by BAC numbers. Panels c-f show chromosomes spreads with FISH mapped BACS. FISH mapped BACS are identified by arrow heads on labelled chromosomes. Idiograms for all S. mansoni chromosomes are included in the Supplementary Online Materials.

Figure 2. Intron size distribution

The length of introns varies according to their position in a transcript, counting from the 5′ end (solid circles) and the 3′ end (open circles). After approximately 5 introns, the length difference is no longer apparent due to the variation in the number of introns per transcript (See Supplementary Information).

Figure 3. Schematic representation of gene structure from MEG family members

a, Structure of a representative member from each MEG family. Where multiple members were found, the total number detected is indicated in parentheses. Each box represents an exon drawn to scale and the number above it indicates the exon size in nucleotides. For illustrative purposes, the introns are shown with fixed length. Black triangles and diamonds indicate exons encoding predicted signal peptides and transmembrane helices, respectively. Other characteristics associated with exons are indicated by colour and grouped as follow: micro-exons having lengths of either multiples of 3 bp (red) or indivisible by 3 bp (orange); exons longer than 36 bp and having lengths of either multiples of 3 bp (blue) or indivisible by 3 bp (green); putative initiation and termination exons (grey); untranslated region (UTR) (black). Asterisk indicates exon deduced from transcript data, which did not match sequenced genome. MEG-12 and 13 structures were only partially predicted due to the lack of transcripts containing the 5′ end of these genes. b, RT-PCR or EST-based evidence of transcription (black box) for each family across different life cycle stages (G, C, E and M: germball, cercaria, egg and miracidium; 3s and 7s: 3- and 7-day schistosomula; 21li and 28li: 21- and 28-day liver worms; 45a: 45-day adult worm pairs).