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

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