On the evolution of mammalian kininogens

A model for the evolution of mammalian kininogens has been constructed which is based on sequence homology. This model suggests that several gene elements coding for the major constituents of the kininogens, i.e. the heavy chain, the light chain and the kinin segment, arose independently from their progenitors. The heavy chain of the kininogens known to execute their inhibitory function against cysteine proteinases has evolved by gene triplication from an ancestor which is closely related to the present-day form of the low molecular weight cysteine proteinase inhibitor cystatin. Part of the light chain of the mammalian kininogens which contains a unique region extremely rich in histidine and glycine has descended by gene multiplication from smaller units, possibly even from the dipeptide Gly-His. At present, the mode and timepoint of fusion of the various gene elements coding for the various structural constituents of the mammalian kininogens is not known.