THE RECURRING EVOLUTION OF LIPOPROTEIN(A) - INSIGHTS FROM CLONING OF HEDGEHOG APOLIPOPROTEIN(A)

The lipoprotein Lp(a), a major inherited risk factor for atheroscleros is, consists of a low density lipoprotein-like particle containing apo lipoprotein B-100 plus the distinguishing component apolipoprotein(a) (apo(a)). Human apo(a) contains highly repeated domains related to pla sminogen kringle four plus single kringle five and protease-like domai ns, Apo(a) is virtually confined to primates, and the gene may have ar isen during primate evolution. One exception is the occurrence of an L p(a)like particle in the hedgehog. Cloning of the hedgehog apo(a)-like gene shows that it is distinctive in form and evolutionary history fr om human apo(a), but that it has acquired several common features. It appears that the primate and hedgehog apo(a) genes evolved independent ly by duplication and modification of different domains of the plasmin ogen gene, providing a novel type of ''convergent'' molecular evolutio n.