A Systematically Improved High Quality Genome and Transcriptome of the Human Blood Fluke Schistosoma mansoni

Abstract

Schistosomiasis is one of the most prevalent parasitic diseases, affecting millions of people in developing countries. Amongst the human-infective species, Schistosoma mansoni is also the most commonly used in the laboratory and here we present the systematic improvement of its draft genome. We used Sanger capillary and deep-coverage Illumina sequencing from clonal worms to upgrade the highly fragmented draft 380 Mb genome to one with only 885 scaffolds and more than 81% of the bases organised into chromosomes. We have also used transcriptome sequencing (RNA-seq) from four time points in the parasite's life cycle to refine gene predictions and profile their expression. More than 45% of predicted genes have been extensively modified and the total number has been reduced from 11,807 to 10,852. Using the new version of the genome, we identified trans-splicing events occurring in at least 11% of genes and identified clear cases where it is used to resolve polycistronic transcripts. We have produced a high-resolution map of temporal changes in expression for 9,535 genes, covering an unprecedented dynamic range for this organism. All of these data have been consolidated into a searchable format within the GeneDB ( www.genedb.org) and SchistoDB ( www.schistodb.net) databases. With further transcriptional profiling and genome sequencing increasingly accessible, the upgraded genome will form a fundamental dataset to underpin further advances in schistosome research.

Author Summary

Schistosomiasis is a disease caused by parasitic blood flukes of the genus Schistosoma. Human-infective species are prevalent in developing countries, where they represent a major disease burden as well as an impediment to socioeconomic development. In addition to its clinical relevance, Schistosoma mansoni is the species most widely used for laboratory experimentation. In 2009, the first draft of the S. mansoni and S. japonicum genomes were published. Both genome sequences represented a great step forward for schistosome research, but their highly fragmented nature compromised the quality of potential downstream analyses. In this study, we have substantially improved both the genome and the transcriptome resources for S. mansoni. We collated existing data and added deep DNA sequence data from clonal worms and RNA sequence data from four key time points in the life cycle of the parasite. We were able to identify transcribed regions to single-base resolution and have profiled gene expression from the free-living larvae to the early human parasitic stage. We uncovered extensive use of single transcripts from multiple genes, which the organism subsequently resolves by trans-splicing. All data from this study comprise a major new release of the genome, which is publicly and easily accessible.