Accelerated Evolution of Schistosome Genes Coding for Proteins Located at the Host–Parasite Interface

Abstract

Study of proteins located at the host–parasite interface in schistosomes might provide clues about the mechanisms utilized by the parasite to escape the host immune system attack. Micro-exon gene (MEG) protein products and venom allergen-like (VAL) proteins have been shown to be present in schistosome secretions or associated with glands, which led to the hypothesis that they are important components in the molecular interaction of the parasite with the host. Phylogenetic and structural analysis of genes and their transcripts in these two classes shows that recent species-specific expansion of gene number for these families occurred separately in three different species of schistosomes. Enrichment of transposable elements in MEG and VAL genes in Schistosoma mansoni provides a credible mechanism for preferential expansion of gene numbers for these families. Analysis of the ratio between synonymous and nonsynonymous substitution rates (dN/dS) in the comparison between schistosome orthologs for the two classes of genes reveals significantly higher values when compared with a set of a control genes coding for secreted proteins, and for proteins previously localized in the tegument. Additional analyses of paralog genes indicate that exposure of the protein to the definitive host immune system is a determining factor leading to the higher than usual dN/dS values in those genes. The observation that two genes encoding S. mansoni vaccine candidate proteins, known to be exposed at the parasite surface, also display similar evolutionary dynamics suggests a broad response of the parasite to evolutionary pressure imposed by the definitive host immune system.

Exploring molecular variation in Schistosoma japonicum in China

“…Therefore, based on the present findings, we support recommendations 62 63 that, in addition to assessing variation between species 64 65 , comprehensive assessments of intraspecific conservation in immunogens or their protective epitopes should precede the research and development of any schistosome vaccine, in order to provide an informed position and some confidence that a vaccine would be efficacious in the field. Although our focus here was principally on immunogenic molecules, similar considerations would apply to targets for the development of new anti-schistosomal drugs.…”

Evidence That Rhesus Macaques Self-Cure from a Schistosoma japonicum Infection by Disrupting Worm Esophageal Function: A New Route to an Effective Vaccine?

“…They provide a clear explanation for the cessation of feeding that leads to worm starvation and death and they implicate the protein products of MEGs as likely targets. A recent study has revealed that this group of genes has been subjected to greater selective pressure than any other during evolution of the Genus Schistosoma [ 40 ]. It is tempting to conclude that the host immune system has applied the pressure mainly on the esophagus, where the battle has been waged.…”

What’s in SWAP? Abundance of the principal constituents in a soluble extract of Schistosoma mansoni revealed by shotgun proteomics

“…Recently, the rate of evolution of schistosome proteins has been investigated using the dN/dS ratio of nucleotide substitutions as the criterion of selection pressure, in the three major schistosome species that infect humans [ 39 ]. The study revealed that genes encoding exposed micro-exon gene (MEG) proteins and some venom allergen-like (VAL) proteins had the highest ratios, compared to genes encoding internal proteins and gastrodermal secretions.…”