Molecular evolution of myotoxic phospholipases A₂ from snake venom

After two decades of study, we draw the conclusion that venom-gland phospholipase A₂ (PLA₂) isozymes, including PLA ₂ myotoxins of Crotalinae snakes, have evolved in an accelerated manner to acquire their diverse physiological activities. In this review, we describe how accelerated evolution of venom PLA₂ isozymes was discovered. This type of evolution is fundamental for other venom isozyme systems. Accelerated evolution of venom PLA₂ isozyme genes is due to rapid change in exons, but not in introns and the flanking regions, being completely opposite to the case of the ordinary isozyme genes. The molecular mechanism by which proper base substitutions had occurred in the particular sites of venom isozyme genes is a puzzle to be solved in future studies. It should be noted that accelerated evolution occurred until the isozymes had acquired their particular function and, since then, they have evolved with less frequent mutation, possibly for functional conservation. We also found that interisland mutations occurred in venom PLA₂ isozymes. The relationships between mutation and its driving force are speculative and the real mechanism remains a mystery.