A novel hypothesis regarding the evolutionary origins of the immunoglobulin fold

The recent cloning of two cDNAs (Clone 1 and Clone 5) that encode novel hyp othetical proteins, combining an N-terminal Ig kappa-like domain with featu res that occur in microfibril-associated glycoproteins (MAGPs) and fibrinog en, raises the question of whether the Ig fold may have originated in assoc iation with functions that may be more primitive than soluble immunity. Pai rwise alignments were performed to compare similarities of fibrinogen-beta, Clone I and an Ig kappa sequence. Clone I had two regions in its Ig domain with > 50% similarity to fibrinogen, while Ig kappa was virtually non-homo logous to fibrinogen. This result suggests that Clone I is closer to their common ancestor. A neighbour-joining tree was computed, and it supported th is interpretation. Three-dimensional modelling of the most highly conserved sequence revealed two antiparallel beta strands connected by a helix. Thes e observations suggest that the ancestral gene for the immunoglobulin super family may have originated as a primitive sandwich-like fold, possibly wed in matrix/cell communications.