APOLIPOPROTEIN(A) - A PUZZLING EVOLUTIONARY STORY

Human apolipoprotein(a), a risk factor for heart disease, has over 80% sequence identity to plasminogen. Plasminogen contains five distinct kringle domains plus a catalytic protease subunit. Human apo(a) consis ts of multiple copies (the number varies in individuals) of a domain r esembling kringle 4, a single copy of a domain resembling kringle 5, a nd a protease-like domain. The recently cloned hedgehog version of apo lipoprotein(a), which contains 31 nearly identical copies of plasminog en kringle 3 and lacks a protease domain, has prompted us to investiga te the evolutionary history of the apolipoprotein (a) gene in mammals. Our analysis supports the nonfunctionality of the human apolipoprotei n(a) protease domain, and a single (or multiple) duplication of plasmi nogen gene before mammal radiation, which originated apolipoprotein(a) in mammals.