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.