Ohno Motonori, Chijiwa Takahito, Oda-Ueda Naoko, Ogawa Tomohisa, Hattori Shosaku
Department of Applied Life Science, Faculty of Engineering, Sojo University, Kumamoto 860-0082, Japan.
Toxicon. 2003 Dec 15;42(8):841-54. doi: 10.1016/j.toxicon.2003.11.003.
After two decades of study, we draw the conclusion that venom-gland phospholipase A2 (PLA2) isozymes, including PLA2 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.
经过二十年的研究，我们得出结论：毒液腺磷脂酶A2（PLA2）同工酶，包括蝰蛇科蛇类的PLA2肌毒素，已经以加速的方式进化以获得其多样的生理活性。在这篇综述中，我们描述了毒液PLA2同工酶加速进化是如何被发现的。这种进化类型对于其他毒液同工酶系统来说是至关重要的。毒液PLA2同工酶基因的加速进化是由于外显子的快速变化，而非内含子和侧翼区域，这与普通同工酶基因的情况完全相反。毒液同工酶基因特定位点发生适当碱基替换的分子机制是未来研究中有待解决的难题。应当注意的是，加速进化一直持续到同工酶获得其特定功能，从那时起，它们以较低频率的突变进化，这可能是为了功能保守。我们还发现毒液PLA2同工酶中发生了岛屿间突变。突变与其驱动力之间的关系只是推测性的，真正的机制仍然是个谜。
