The cardiovascular risk factor LPA has a puzzling distribution among mammals, its presence being limited to a subset of primates and a member of the insectivore lineage, the hedgehog. To explore the evolutionary history of LPA, we performed extensive genomic sequence comparisons of multiple species with and without an LPA gene product, such as human, baboon, hedgehog, lemur, and mouse. This analysis indicated that LPA arose independently in a subset of primates, including baboon and human, and an insectivore, the hedgehog, and was not simply lost by species lacking it. The similar structural domains shared by the hedgehog and primate LPA indicate that they were formed by a unique molecular mechanism involving the convergent evolution of paralogous genes in these distant species. (C) 2003 Elsevier Inc. All rights reserved.