Genome-wide discovery, and computational and transcriptional characterization of an AIG gene family in the freshwater snail Biomphalaria glabrata, a vector for Schistosoma mansoni

Abstract

Background: The AIG (avrRpt2-induced gene) family of GTPases, characterized by the presence of a distinctive AIG1 domain, is mysterious in having a peculiar phylogenetic distribution, a predilection for undergoing expansion and loss, and an uncertain functional role, especially in invertebrates. AIGs are frequently represented as GIMAPs (GTPase of the immunity associated protein family), characterized by presence of the AIG1 domain along with coiled-coil domains. Here we provide an overview of the remarkably expanded AIG repertoire of the freshwater gastropod Biomphalaria glabrata, compare it with AIGs in other organisms, and detail patterns of expression in B. glabrata susceptible or resistant to infection with Schistosoma mansoni, responsible for the neglected tropical disease of intestinal schistosomiasis. Results: We define the 7 conserved motifs that comprise the AIG1 domain in B. glabrata and detail its association with at least 7 other domains, indicative of functional versatility of B. glabrata AIGs. AIG genes were usually found in tandem arrays in the B. glabrata genome, suggestive of an origin by segmental gene duplication. We found 91 genes with complete AIG1 domains, including 64 GIMAPs and 27 AIG genes without coiled-coils, more than known for any other organism except Danio (with > 100). We defined expression patterns of AIG genes in 12 different B. glabrata organs and characterized whole-body AIG responses to microbial PAMPs, and of schistosome-resistant or-susceptible strains of B. glabrata to S. mansoni exposure. Biomphalaria glabrata AIG genes clustered with expansions of AIG genes from other heterobranch gastropods yet showed unique lineage-specific subclusters. Other gastropods and bivalves had separate but also diverse expansions of AIG genes, whereas cephalopods seem to lack AIG genes. Conclusions: The AIG genes of B. glabrata exhibit expansion in both numbers and potential functions, differ markedly in expression between strains varying in susceptibility to schistosomes, and are responsive to immune challenge. These features provide strong impetus to further explore the functional role of AIG genes in the defense responses of B. glabrata, including to suppress or support the development of medically relevant S. mansoni parasites.

Genomic and transcriptional analysis of genes containing fibrinogen and IgSF domains in the schistosome vector Biomphalaria glabrata, with emphasis on the differential responses of snails susceptible or resistant to Schistosoma mansoni

“…For instance, RES snails do not have dramatically higher resting levels of FREPs than SUS snails. This is somewhat in contrast to our recent study of GTPase IMAP family members (GIMAPs) showing that over 20 members of this gene family are constitutively expressed at significantly higher levels in RES than in SUS snails, in both juvenile and adult stages [ 84 ]. Although normalized read counts may not provide the best indicator of true relative abundance among various FReD transcripts, it is clear that some FREPs are expressed at higher constitutive levels than others.…”

“…mansoni exposure, a comprehensive transcriptomics analysis was carried out. Snails and experimental treatments used in this study are described in Lu et al [ 84 ]. Briefly, uninfected juveniles (5-8mm in diameter) of lab-reared RES (BS-90) and SUS (M line) B .…”

“…An overview of snail samples per group and sequencing information is summarized in S1 Table . See Lu et al [ 84 ] for a detailed description of sample collection, RNA and DNA extraction, library preparation, and differential gene expression analyses. Genes were considered differentially expressed in comparisons with cutoff values using fold change (FC) ≥2 (absolute log2FC ≥1), and a posterior probability of differential expression (PPDE) ≥0.95 for EBSeq analysis.…”

The GIMAP Family Proteins: An Incomplete Puzzle

“…GTPases with similarities to mammalian GIMAPs appear to have evolved independently in different species (56,58,59,(149)(150)(151)(152).…”

“…In mice and rats the Gimap genes are present as a tight cluster within a 150kb region on chromosome 6 and 4, respectively (2,3). Gimap-like genes have been identified in angiosperms, corals, nematodes and in snails wherein they are implicated in protection from infections (56)(57)(58)(59). The observed homology between GIMAP proteins and the plant avrRpt2 induced gene 1 (AIG1) might have resulted from convergent evolution of the AIG1 domain (4,60).…”