Identification of G protein-coupled receptors in Schistosoma haematobium and S. mansoni by comparative genomics

Abstract

BackgroundSchistosomiasis is a parasitic disease affecting ~200 million people worldwide. Schistosoma haematobium and S. mansoni are two relatively closely related schistosomes (blood flukes), and the causative agents of urogenital and hepatointestinal schistosomiasis, respectively. The availability of genomic, transcriptomic and proteomic data sets for these two schistosomes now provides unprecedented opportunities to explore their biology, host interactions and schistosomiasis at the molecular level. A particularly important group of molecules involved in a range of biological and developmental processes in schistosomes and other parasites are the G protein-coupled receptors (GPCRs). Although GPCRs have been studied in schistosomes, there has been no detailed comparison of these receptors between closely related species. Here, using a genomic-bioinformatic approach, we identified and characterised key GPCRs in S. haematobium and S. mansoni (two closely related species of schistosome).MethodsUsing a Hidden Markov Model (HMM) and Support Vector Machine (SVM)-based pipeline, we classified and sub-classified GPCRs of S. haematobium and S. mansoni, combined with phylogenetic and transcription analyses.ResultsWe identified and classified classes A, B, C and F as well as an unclassified group of GPCRs encoded in the genomes of S. haematobium and S. mansoni. In addition, we characterised ligand-specific subclasses (i.e. amine, peptide, opsin and orphan) within class A (rhodopsin-like).ConclusionsMost GPCRs shared a high degree of similarity and conservation, except for members of a particular clade (designated SmGPR), which appear to have diverged between S. haematobium and S. mansoni and might explain, to some extent, some of the underlying biological differences between these two schistosomes. The present set of annotated GPCRs provides a basis for future functional genomic studies of cellular GPCR-mediated signal transduction and a resource for future drug discovery efforts in schistosomes.

Proteomic analysis of differentially expressed proteins in the marine fish parasitic ciliate Cryptocaryon irritans

“…Even though there was no direct proof that actin in ciliates could evoke the host immunity against ciliates infection, mice immunized with a recombinant actin-depolymerizing factor (ADF) of C. irritans produced specific antibodies against this protein (Huang et al, 2013). In addition, tubulin and actin could mediate heterotrimeric G protein signal transduction and result to the interplay of signaling pathways and cytoskeletal dynamics, in which the parasite G proteins-coupled receptors were identified as an antigen against host humoral antibodies (Campos et al, 2014;Schappi et al, 2014). Therefore, actin and tubulin, both of which are present in C. irritans, might be utilized as targets for vaccine development to control cryptocaryoniasis.…”

Profiling G protein-coupled receptors of Fasciola hepatica identifies orphan rhodopsins unique to phylum Platyhelminthes

“…Despite two F. hepatica genomes [18,19], no GPCR sequences have been reported from F. hepatica. In contrast, GPCRs have been profiled in the genomes of trematodes ( Schistosoma mansoni and Schistosoma haematobium [20,21]), cestodes ( Echinococcus multilocularis, E. granulosus, Taenia solium and Hymenolepis microstoma [22]), and planaria ( Schmidtea mediterranea, Girardia tigrina [21–24]). These datasets illustrated clear differences in the GPCR complements of individual flatworm classes and species, with reduced complements in parasitic flatworms compared to planarians.…”

GPCR and IR genes in Schistosoma mansoni miracidia

“…Of these, experimental validation has been established for the histamine receptor (Smp_043260) [60]. Regarding the other GPCRs identified in this study, three (Smp_203500,Smp_204230 and Smp_178420) have not been described previously, while Smp_173010 was reported by Campos et al [25] as novel platyhelminth-specific rhodopsin-like orphan family (PROF). This variation can be explained by the different workflow for curation of the final GPCR list, whereby receptors were only taken if they satisfied requirements within all of TMHMM, HMM and Phobius tools.…”

“…All encode proteins considered as full-length, as determined by the presence of 7-TM domains, putative rhodopsin-type GPCR domains, as well as a methionine start and a stop codon. Table 2 also shows the amino acid identity with the identifiable homologs in the closely related S. haematobium [25]. Of the three new orphan GPCRs described in this paper, (i) Smp_203500 shares significant homology (95 % identity) with an allatostatin-A receptor (GenBank XP_012796783.1), (ii) Smp_204230 shares significant homology (87 % identity) with a S. haematobium hypothetical protein (GenBank XP_012798047.1), and (iii) Smp_178420 also shares significant homology (85 % identity) with a S. haematobium hypothetical protein (Genbank XP_012791982.1).…”

“…In 2011, the S. mansoni draft genome set was systematically upgraded with more than 45 % of predicted genes extensively modified and the total number reduced from 11,807 to 10,852 [24]. Employing comparative genomics, platyhelminth GPCRs have been identified and characterized for S. mansoni and S. haematobium [25]. Of those, the opsins are rhodopsin-type GPCRs that were inferred to be involved in photoreception, typically thought of as light-absorbing proteins that act as light sensors in animals [26–28].…”