Derivatives of the lectin complement pathway in Lophotrochozoa

A plethora of non-overlapping immune molecular mechanisms in metazoans is the most puzzling issue in comparative immunobiology. No valid evolutionary retrospective on these mechanisms has been developed. In this study, we aimed to reveal the origin and evolution of the immune complement-like system in Lophotrochozoa. For this, we analyzed publicly available transcriptomes of prebilaterian and lophotrochozoan species, mapping lineage-specific molecular events on the phylogenetic tree. We found that there were no orthologs of mannose-binding lectin (MBL) and ficolins (FCN) in Lophotrochozoa but C1q-like proteins (C1qL), bearing both a collagen domain and a globular C1q domain, were omnipresent in them. This suggests that among all complement-like activators the C1qL-specific domain architecture was an evolutionarily first. Two novel protostomian MASP-Related Molecules, MReM1 and MReM2, might hypothetically compensate for the loss of a prebilaterian MASP-orthologous gene and act in complex with C1qL and C1qDC as a "proto-activator" of an ancient "proto-complement". We proposed a new model of the complement evolution predicting that numerous lineage-specific complement-like systems should have evolved from a stem "antique" molecular complex. First evolved in the common ancestor of coelomic animals, the "antique" humoral complex consisted of a TEP molecule, the common ancestor of TEP-associated proteases (C2/Bf/Сf/Lf), the common ancestor of MASP-like proteases (MASP/C1r/C1s, MReM1/MReM2) and multimeric recognition proteins (C1q-, MBL- and FCN-homologs). Further evolutionary specialization and expansion of the complex was independent and lineage-specific, examples being the mammalian complement system and the Apogastropoda complement-like complex. The latter includes an impressive array of multimeric recognition proteins, the variable immunoglobulin and lectin domain containing molecules (VIgL), homologous to C1q, MBL, FCN and other lectins. Four novel polymorphic subfamilies of VIgLs were found to be expressed in Apogastropoda: C1q-related proteins (QREP), zona pellucida-related proteins (ZREP), Scavenger Receptor Cys-Rich-related proteins (SREP) and HPA-lectin related proteins (HREP). The transcriptional response of fibrinogen-related proteins of VIgL family (LlFREP), LlQREP and LlSREP to infestation of common periwinkle, Littorina littorea, with digenean parasite Himasthla elongata correlates with that of LlMReM1, supporting the model suggested in this study.