Abstract
Schistosomiasis is a debilitating parasitic disease infecting hundreds of millions of people. Schistosomes use aquatic snails as intermediate hosts. A promising avenue for disease control involves leveraging innate host mechanisms to reduce snail vectorial capacity. In a genome-wide association study of Biomphalaria glabrata snails, we identify genomic region PTC2 which exhibits the largest known correlation with susceptibility to parasite infection (>15 fold effect). Using new genome assemblies with substantially higher contiguity than the Biomphalaria reference genome, we show that PTC2 haplotypes are exceptionally divergent in structure and sequence. This variation includes multi-kilobase indels containing entire genes, and orthologs for which most amino acid residues are polymorphic. RNA-Seq annotation reveals that most of these genes encode single-pass transmembrane proteins, as seen in another resistance region in the same species. Such groups of hyperdiverse snail proteins may mediate host-parasite interaction at the cell surface, offering promising targets for blocking the transmission of schistosomiasis.
Highlights
Schistosomiasis is a chronic and debilitating disease suffered by over 200 million people worldwide (Evan Secor, 2014; Lo et al, 2018)
In pooled whole-genome sequencing of 600 infected and 600 uninfected 13–16-R1 snails (298x and 333x coverage, respectively), a single genomic region showed by far the greatest difference in allele frequencies between pools (Figure 1A; Supplementary file 1A)
The highest outliers occurred in a 450 kb section of Linkage Group (LG) XII, here called Polymorphic Transmembrane Cluster 2 (PTC2)
Summary
Schistosomiasis is a chronic and debilitating disease suffered by over 200 million people worldwide (Evan Secor, 2014; Lo et al, 2018). Epidemiology and Global Health Genetics and Genomics eLife digest Schistosomiasis is a widespread parasitic disease, affecting over 200 million people in tropical countries It is caused by schistosome worms, which are carried by freshwater snails. Strain specificity may be conveyed by suites of highly diverse host genes that act synergistically, especially if these interact with varying and coevolving sets of parasite genes to mediate host-parasite recognition (Schmid-Hempel, 2005; Schulenburg et al, 2007; Cerenius and Soderhall, 2013) Such loci will not necessarily produce a large phenotypic signal unless several are clustered in the same genomic region. These results support a general immunogenetic scenario in which clusters of highly polymorphic TM1 genes mediate host-parasite interaction
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