Evolutionary relationships and implications for the regulation of phospholipase A2 from snake venom to human secreted forms.

The amino acid sequences of 40 secreted phospholipase A2's (PLA2) were aligned and a phylogenetic tree derived that has three main branches corresponding to elapid (group I), viperid (group II), and insect venom types of PLA2. The human pancreatic and recently determined nonpancreatic sequences in the comparison align with the elapid and viperid categories, respectively, indicating that at least two PLA2 genes existed in the vertebrate line before the divergence of reptiles and mammals about 200-300 million years ago. This allows resolution for the first time of major genetic events in the evolution of current PLA2's and the relationship of human PLA2's to those of snake venom, many of which are potent toxins. Implications for possible mechanisms of regulation of mammalian intra- and extracellular PLA2's are discussed, as well as issues relating to the search for the controlling enzymes in arachidonic acid release, prostaglandin generation, and signal transduction.