Adaptation and diversification of venomous snake proteins

Abstract

According to the World Health Organization, approximately 1.8–2.7 million people worldwide suffer from venomous snake bites each year and at least 138,000 of these incidents are fatal. Whereas, snakebite envenoming poses a serious threat to public health, yet the snake venom toxins endow several pharmacological effects, including presynaptic neurotoxicity, myotoxicity, and cardiotoxicity, as well as anticoagulant, hemolytic, hemorrhagic, edema-inducing, and platelet aggregation-inhibiting effects. Duplication and mutation of the genes encoding these toxins play an important role in generating molecular diversity. Curiously, venomous snakes are not lethal to the viper itself because the viper’s resistance against its own venom. However, endogenous inhibitor proteins evolutionarily acquired by venomous snakes to protect themselves have not yet been fully characterised because it is unclear how to inhibit for target toxin due to the lack of information including mutation analysis and the three-dimensional structures of the inhibitors. This review provides an overview of endogenous inhibitors of venomous snake as regulation systems for the toxin proteins. Recently, we isolated some inhibitors targeting different toxins from the sera of the Japanese vipers. We investigated the evolution of these endogenous inhibitors, which have been significantly influenced by positive selection. Directional mutagenesis, where mutation hotspots are found in genes encoding molecular surface proteins and functional domains of these proteins, acts as a diversifying mechanism for the exquisite biological targeting necessary to protect the host from its own venom.