The evolutionary history of Ephs and ephrins: toward multicellular organisms

More about Open Access at the Crick

Abstract

Eph receptor (Eph) and ephrin signalling regulates fundamental developmental processes through both forward and reverse signalling triggered upon cell-cell contact. In vertebrates, they are both classified into classes A and B, and some representatives have been identified in many metazoan groups, where their expression and functions have been well studied. We have extended previous phylogenetic analyses and examined the presence of Eph and ephrins in the tree of life to determine their origin and evolution. We have found that (i) premetazoan choanoflagellates may already have rudimental Eph/ephrin signalling as they have an Eph-/ephrin-like pair and homologues of downstream signalling genes; (ii) both forward and reverse downstream signalling might already occur in Porifera since sponges have most genes involved in these types of signalling; (iii) the non-vertebrate metazoan Eph is a type-B receptor that can bind ephrins regardless of their membrane anchoring structure, glycosylphosphatidylinositol or transmembrane; (iv) Eph/ephrin cross-class binding is specific to Gnathostomata and (v) kinase-dead Eph receptors can be traced back to Gnathostomata. We conclude that Eph/ephrin signalling is of older origin than previously believed. We also examined the presence of protein domains associated with functional characteristics and the appearance and conservation of downstream signalling pathways to understand the original and derived functions of Ephs and ephrins. We find that the evolutionary history of these gene families points to an ancestral function in cell-cell interactions that could contribute to the emergence of multicellularity and, in particular, to the required segregation of cell populations.