CONVERGENT EVOLUTION OF APOLIPOPROTEIN(A) IN PRIMATES AND HEDGEHOG

Apolipoprotein(a) [apo(a)] is the distinguishing protein component of lipoprotein(a), a major inherited risk factor for atherosclerosis. Hum an apo(a) is homologous to plasminogen. It contains from 15 to 50 repe ated domains closely related to plasminogen kringle four, plus single kringle five-like and inactive protease-like domains, This expressed g ene is confined to a subset of primates. Although most mammals lack ap o(a), hedgehogs produce an apo(a)-like protein composed of highly repe ated copies of a plasminogen kringle three-like domain, with complete absence of protease domain sequences, Both human and hedgehog apo(a)-l ike proteins form covalently linked lipoprotein particles that can bin d to fibrin and other substrates shared with plasminogen, DNA sequence comparisons and phylogenetic analysis indicate that the human type of apo(a) evolved from a duplicated plasminogen gene during recent prima te evolution. In contrast, the kringle three-based type of apo(a) evol ved from an independent duplication of the plasminogen gene approximat ely 80 million years ago. In a type of convergent evolution, the plasm inogen gene has been independently remodeled twice during mammalian ev olution to produce similar forms of apo(a) in two widely divergent gro ups of species.