RESEARCH ARTICLE Hyperdiverse Gene Cluster in Snail Host Conveys Resistance to Human Schistosome Parasites

Schistosomiasis, a neglected global pandemic, may be curtailed by blocking transmission of the parasite via its intermediate hosts, aquatic snails. Elucidating the genetic basis of snail-schistosome interaction is a key to this strategy. Here we map a natural parasite-resis-tance polymorphism from a Caribbean population of the snail Biomphalaria glabrata. In in-dependent experimental evolution lines, RAD genotyping shows that the same genomic region responds to selection for resistance to the parasite Schistosoma mansoni. A domi-nant allele in this region conveys an 8-fold decrease in the odds of infection. Fine-mapping and RNA-Seq characterization reveal a<1Mb region, the Guadeloupe Resistance Com-plex (GRC), with 15 coding genes. Seven genes are single-pass transmembrane proteins with putative immunological roles, most of which show strikingly high nonsynonymous di-vergence (5-10%) among alleles. High linkage disequilibrium among three intermediate-fre-quency (>25%) haplotypes across the GRC, a significantly non-neutral pattern, suggests that balancing selection maintains diversity at the GRC. Thus, the GRC resembles immune gene complexes seen in other taxa and is likely involved in parasite recognition. The GR