Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan; Department of Biostatistics, University of Oslo, Oslo, Norway
Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan
I-Jin Lin
Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan
Kun-Yi Chien
Graduate Institute of Biomedical Sciences, Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, Taiwan
Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan; Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan; Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan
Wen-Guey Wu
Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan; Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan
For decades, studies of snake venoms focused on the venom-ome-specific toxins (VSTs). VSTs are dominant soluble proteins believed to contribute to the main venomous effects and emerged into gene clusters for fast adaptation and diversification of snake venoms. However, the conserved minor venom components, such as snake venom phosphodiesterase (svPDE), remain largely unexplored. Here, we focus on svPDE by genomic and transcriptomic analysis across snake clades and demonstrate that soluble svPDE is co-opted from the ancestral membrane-attached ENPP3 (ectonucleotide pyrophosphatase/phosphodiesterase 3) gene by replacing the original 5′ exon with the exon encoding a signal peptide. Notably, the exons, promoters, and transcription/translation starts have been replaced multiple times during snake evolution, suggesting the evolutionary necessity of svPDE. The structural and biochemical analyses also show that svPDE shares the similar functions with ENPP family, suggesting its perturbation to the purinergic signaling and insulin transduction in venomous effects.
