The Schistosoma japonicum genome reveals features of host-parasite interplay

Abstract

Schistosoma japonicum is a parasitic flatworm that causes human schistosomiasis, which is a significant cause of morbidity in China and the Philippines. Here we present a draft genomic sequence for the worm. The genome provides a global insight into the molecular architecture and host interaction of this complex metazoan pathogen, revealing that it can exploit host nutrients, neuroendocrine hormones and signalling pathways for growth, development and maturation. Having a complex nervous system and a well-developed sensory system, S. japonicum can accept stimulation of the corresponding ligands as a physiological response to different environments, such as fresh water or the tissues of its intermediate and mammalian hosts. Numerous proteases, including cercarial elastase, are implicated in mammalian skin penetration and haemoglobin degradation. The genomic information will serve as a valuable platform to facilitate development of new interventions for schistosomiasis control.

Figure 1. Functional categorization of S. japonicum genes and protein domain analysis

a, Proportion of the 6,972 S. japonicum proteins with functional information in different GO categories. b, In S. japonicum, vertebrates (H. sapiens, G. gallus, and D. rerio), insects (D. melanogaster, and A. gambiae), C. elegans, and N. vectensis, a total of 7,562 domains were detected. The majority of S. japonicum domains are shared with other taxa, having the least unique domains, whereas vertebrates evolved significant numbers of unique protein domains.

Figure 2. The distribution of categories and composition of repeat elements in S. japonicum genome

Retrons, retrotransposons; LTR, long terminal repeat; SINE, short interspersed nuclear element.

Figure 3. Putative signaling pathways for growth, development and neuroactive ligand-receptor interaction in S. japonicum

The pathways for growth and development (indicated with different colors), and the neuroactive ligand-receptor interactions in S. japonicum are shown on the left and right, respectively. Abbreviations: FRP, frizzled-related protein 1; ProC, porcupine homolog (Drosophila); 5-HT, 5-hydroxytryptamine; AChR, acetylcholine receptor; GlyR, glycine receptor; GluR, glutamate receptor; mGlu, metabotropic glutamate receptor; INSR, insulin receptor; HR, histamine receptor; GABA, gamma aminobutyric acid; PLC, phospholipase C; CaMK, calcium/calmodulin-dependent protein kinase; GNAS, guanine nucleotide binding protein (G protein), alpha stimulating; PKA, protein kinase A; NICD, notch intracellular domain; GSK3β, glycogen synthase kinase 3 beta; TCF, transcription factor 7; ZIC2, zinc finger protein.

Figure 4. Putative neuroendocrine system in S. japonicum

The schematic was drawn according to the proposed hypothalamus-pituitary-peripheral endocrine glands axis with putative ligands found in S. japonicum colored in orange and S. japonicum receptors in yellow. Abbreviations: CRH, corticotrophin releasing hormone; GHRH, growth hormone releasing hormone; TRH, thyrotropin-releasing hormone; TSH, thyroid stimulating hormone; GnRH, gonadotropin releasing hormone; PRH, prolactin releasing hormone; FSH, follicle stimulating hormone.

Figure 5. S. japonicum proteases and elastase

a, The pie chart shows the distribution of the five kinds of proteases. b, The genomic structure of S. japonicum elastase (SjCE). c, A phylogeny of the elastase family in schistosomes using the neighbor-joining method. Bootstrap values are provided above the branches. d, Immunofluorescence assay showing the presence (white arrow) of SjCE around a schistosomulum following its penetration through mouse skin (panel 2). A naïve fluorescein-labelled rabbit serum was used as negative control (panel 4). The location of the cercaria is indicated (arrow). Panels 1 and 3 show the skin tissue slices before addition of labelled antibodies.