The evolution and structure of snake venom phosphodiesterase (svPDE) highlight its importance in venom actions

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Abstract

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.

Data availability

The CDS and peptides of N. atra svPDE revealed in this study have been presented in Figure 1-figure supplement 1. The signal peptides of svPDE in different snake species identified with the public genome assemblies have been shown in Figure 1-figure supplement 3. The newly identified first exon for each species could be retrieved by searching its corresponding genome assembly (NCBI accessions in Supplementary File 1).

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Cheng-Tsung Pan

Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan

Competing interests
The authors declare that no competing interests exist.
Chien-Chu Lin

Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-0647-427X
I-Jin Lin

Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan

Competing interests
The authors declare that no competing interests exist.
Kun-Yi Chien

Department of Biochemistry and Molecular Biology, Chang Gung University, Taoyuan, Taiwan

Competing interests
The authors declare that no competing interests exist.
Yeong-Shin Lin

Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan

For correspondence
yslin@nycu.edu.tw

Competing interests
The authors declare that no competing interests exist.
Hsiao-Han Chang

Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan

For correspondence
hhchang@life.nthu.edu.tw

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-8016-1530
Wen-Guey Wu

Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan

For correspondence
wgwu@life.nthu.edu.tw

Competing interests
The authors declare that no competing interests exist.

Funding

Ministry of Education (Higher Education SPROUT Project)

I-Jin Lin
Hsiao-Han Chang
Wen-Guey Wu

Ministry of Education (Yushan Scholar Program)

Cheng-Tsung Pan
Hsiao-Han Chang

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: One male Taiwan cobra, raised by Tainan World Snake King Educational Farm, was donated by Tainan County Government and the permit was granted by Hsinchu City Animal Protection and Health Inspection office for this study. The animal use protocol was approved by the Institutional Animal Care and Use Committee of National Tsing Hua University (IACUC Protocol No. 11003H010 and Approval No. 110010).

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.