Department of Mammalogy, American Museum of Natural History, New York, NY 10024, USA.
Biol Rev Camb Philos Soc. 2012 Nov;87(4):822-37. doi: 10.1111/j.1469-185X.2012.00222.x. Epub 2012 Mar 10.
Mammals that prey on venomous snakes include several opossums (Didelphidae), at least two hedgehogs (Erinaceidae), several mongooses (Herpestidae), several mustelids, and some skunks (Mephitidae). As a group, these taxa do not share any distinctive morphological traits. Instead, mammalian adaptations for ophiophagy seem to consist only in the ability to resist the toxic effects of snake venom. Molecular mechanisms of venom resistance (as indicated by biochemical research on opossums, mongooses, and hedgehogs) include toxin-neutralizing serum factors and adaptive changes in venom-targeted molecules. Of these, toxin-neutralizing serum factors have received the most research attention to date. All of the toxin-neutralizing serum proteins discovered so far in both opossums and mongooses are human α1B-glycoprotein homologs that inhibit either snake-venom metalloproteinases or phospholipase A(2) myotoxins. By contrast, adaptive changes in venom-targeted molecules have received far less attention. The best-documented examples include amino-acid substitutions in mongoose nicotinic acetylcholine receptor that inhibit binding by α-neurotoxins, and amino-acid substitutions in opossum von Willebrand factor (vWF) that are hypothesized to weaken the bond between vWF and coagulopathic C-type lectins. Although multiple mechanisms of venom resistance are known from some species, the proteomic complexity of most snake venoms suggests that the evolved biochemical defences of ophiophagous mammals are likely to be far more numerous than currently recognized. Whereas most previous research in this field has been motivated by the potential for medical applications, venom resistance in ophiophagous mammals is a complex adaptation that merits attention from comparative biologists. Unfortunately, evolutionary inference is currently limited by ignorance about many relevant facts that can only be provided by future research.
以蛇为食的哺乳动物包括几种负鼠（袋鼬科）、至少两种刺猬（猬科）、几种獴（獴科）、几种鼬科动物和一些臭鼬（臭鼬科）。作为一个群体，这些类群没有任何独特的形态特征。相反，哺乳动物对蛇类的食性适应似乎只在于能够抵抗蛇毒的毒性作用。抗蛇毒的分子机制（如对负鼠、獴和刺猬的生化研究所示）包括中和毒素的血清因子和针对毒液的靶分子的适应性变化。在这些机制中，中和毒素的血清因子迄今为止受到了最多的研究关注。迄今为止，在负鼠和獴中发现的所有中和毒素的血清蛋白都是人类α1B-糖蛋白同源物，可抑制蛇毒金属蛋白酶或磷脂酶 A(2)肌毒素。相比之下，针对毒液的靶分子的适应性变化受到的关注要少得多。有文献记载的最好例子包括抑制α-神经毒素结合的獴烟碱型乙酰胆碱受体中的氨基酸取代，以及假设削弱 vWF 与凝血异常 C 型凝集素之间键合的负鼠血管性血友病因子（vWF）中的氨基酸取代。尽管一些物种已知有多种抗蛇毒机制，但大多数蛇毒的蛋白质组复杂性表明，食蛇哺乳动物的进化生物化学防御可能比目前所认识的要多得多。虽然该领域的大多数先前研究都是出于医学应用的潜力，但食蛇哺乳动物的抗蛇毒能力是一种复杂的适应，值得比较生物学家关注。不幸的是，目前的进化推断受到许多相关事实的限制，这些事实只能通过未来的研究提供。
