The other major lineage of protostomes, the Lophotrochozoa, includes prominent groups such as the flatworms, annelids, and mollusks. In the polychete annelid Capitella capitata, TLRs have undergone an expansion to over 100 genes, most of which are similar, suggestive of recent duplication. Another annelid, the leech Helobdella robusta, has only 16 TLR homologs which are not only highly divergent from one another but also are not orthologous to any of the polychete sequences (Davidson et al., 2008) . In the freshwater snail Biomphalaria glabrata, FREPs are encoded by an expanded gene family, and are implicated in defense against gastropod parasites such as digenetic trematodes (Hanington et al., 2010a,b) . In B. glabrata, FREPs are particularly noteworthy for being comprised of juxtaposed IgSF and fibrinogen domains, and for the fact they are somatically diversified during the production of hemocytes by the snails (Zhang et al., 2004) . Expanded families of C-type lectins are present in other mollusks and the bivalve www.frontiersin.org Mytilus edulis is capable of generating diversified forms of the AMP myticin C both within and among individuals (Costa et al., 2009 ). Among invertebrate deuterostomes, the sea urchin has proven surprising in featuring dramatic echinoderm-specific expansion of several recognition molecules (Hibino et al., 2006) . Sea urchins possess >220 TLR genes (vertebrates usually have 21-25), >200 NLRs (mammals have 20-35), >200 SRCR genes (humans have 16; Messier-Solek et al., 2010) , and a novel Sp 185/333 gene family. The latter gene family produces a repertoire of defense proteins more diverse than the sequence diversity encoded in the genes, indicative of the presence of another mechanism to generate diversity (Ghosh et al., 2010) . Sea urchins also possess an NF-κB pathway, lectin and alternative complement pathways and homologs of RAG1 and RAG2, but do not produce immunoglobulins (Ig), T cell receptors (TCRs), or have a major histocompatibility complex (MHC; Hibino et al., 2006) .