Biomphalaria snails are instrumental in transmission of the human blood fluke Schistosoma mansoni. With the World Health Organization's goal to eliminate schistosomiasis as a global health problem by 2025, there is now renewed emphasis on snail control. Here, we characterize the genome of Biomphalaria glabrata, a lophotrochozoan protostome, and provide timely and important information on snail biology. We describe aspects of phero-perception, stress responses, immune function and regulation of gene expression that support the persistence of B. glabrata in the field and may define this species as a suitable snail host for S. mansoni. We identify several potential targets for developing novel control measures aimed at reducing snail-mediated transmission of schistosomiasis.

SummaryThe approximate 30 extant invertebrate phyla have diversified along separate evolutionary trajectories for hundreds of millions of years. Although recent work understandably has emphasized the commonalities of innate defenses, there is also ample evidence, as from completed genome studies, to suggest that even members of the same invertebrate order have taken significantly different approaches to internal defense. These data suggest that novel immune capabilities will be found among the different phyla. Many invertebrates have intimate associations with symbionts that may play more of a role in internal defense than generally appreciated. Some invertebrates that are either long lived or have colonial body plans may diversify components of their defense systems via somatic mutation. Somatic diversification following pathogen exposure, as seen in plants, has been investigated little in invertebrates. Recent molecular studies of sponges, cnidarians, shrimp, mollusks, sea urchins, tunicates, and lancelets have found surprisingly diversified immune molecules, and a model is presented that supports the adaptive value of diversified non-self recognition molecules in invertebrates. Interactions between invertebrates and viruses also remain poorly understood. As we are in the midst of alarming losses of coral reefs, increased pathogen challenge to invertebrate aquaculture, and rampant invertebratetransmitted parasites of humans and domestic animals, we need a better understanding of invertebrate immunology. Vive la différence -invertebrates are a heterogeneous lotOne of the most remarkable developments in the recent history of immunology has been the discovery that the internal defense systems of invertebrates, vertebrates, and even plants share striking similarities. The similarities are most notably among signaling receptors of the Toll/interleukin-1 receptor family and in the signaling pathways involved in orchestrating an innate immune response. For very good reasons, this discovery has been big news: it has been important in revealing how a model invertebrate like Drosophila melanogaster defends itself from bacteria and fungi (1, 2); it is pointing the way to the discovery of a previously unknown and important innate defense system in mammals (3, 4), and it is revealing how Correspondence to:

The freshwater snail Biomphalaria glabrata possesses a diverse family of fibrinogen-related proteins (FREPs), hemolymph polypeptides that consist of one or two amino-terminal immunoglobulin superfamily (IgSF) domains and a carboxyl-terminal fibrinogen domain. Here, we show that the IgSF1 domain of the FREP3 subfamily is diversified at the genomic level at higher rates than those recorded for control genes. All sequence variants are derived from a small set of nine source sequences by point mutation and recombinatorial processes. Diverse FREP3 transcripts are also produced. We hypothesize a mechanism present in snails that is capable of diversifying molecules involved in internal defense.

After infection with the digenetic trematode Echinostoma paraensei, hemolymph of the snail Biomphalaria glabrata contains lectins comprised of 65-kDa subunits that precipitate polypeptides secreted by E. paraensei intramolluscan larvae. Comparable activity is lacking in hemolymph of uninfected snails. Three different cDNAs with sequence similarities to peptides derived from the 65-kDa lectins were obtained and unexpectedly found to encode fibrinogen-related proteins (FREPs). These FREPs also contained regions with sequence similarity to Ig superfamily members. B. glabrata has at least five FREP genes, three of which are expressed at increased levels after infection. Elucidation of components of the defense system of B. glabrata is relevant because this snail is an intermediate host for Schistosoma mansoni, the most widely distributed causative agent of human schistosomiasis. These results are novel in suggesting a role for invertebrate FREPs in recognition of parasite-derived molecules and also provide a model for investigating the diversity of molecules functioning in nonself-recognition in an invertebrate.