Abstract

Availability of snake genome sequences has opened up exciting areas of research on comparative genomics and gene diversity. One of the challenges in studying snake genomes is the acquisition of biological material from live animals, especially from the venomous ones, making the process cumbersome and time-consuming. Here, we report comparative sequence analyses of putative toxin gene homologs from Russell’s viper (Daboia russelii) using whole-genome sequencing data obtained from shed skin. When compared with the major venom proteins in Russell’s viper studied previously, we found 45–100% sequence similarity between the venom proteins and their putative homologs in the skin. Additionally, comparative analyses of 20 putative toxin gene family homologs provided evidence of unique sequence motifs in nerve growth factor (NGF), platelet derived growth factor (PDGF), Kunitz/Bovine pancreatic trypsin inhibitor (Kunitz BPTI), cysteine-rich secretory proteins, antigen 5, andpathogenesis-related1 proteins (CAP) and cysteine-rich secretory protein (CRISP). In those derived proteins, we identified V11 and T35 in the NGF domain; F23 and A29 in the PDGF domain; N69, K2 and A5 in the CAP domain; and Q17 in the CRISP domain to be responsible for differences in the largest pockets across the protein domain structures in crotalines, viperines and elapids from the in silico structure-based analysis. Similarly, residues F10, Y11 and E20 appear to play an important role in the protein structures across the kunitz protein domain of viperids and elapids. Our study highlights the usefulness of shed skin in obtaining good quality high-molecular weight DNA for comparative genomic studies, and provides evidence towards the unique features and evolution of putative venom gene homologs in vipers.

Highlights

  • Snake venom genes and their products offer an excellent model system to study gene duplication, evolution of regulatory DNA sequences, and biochemical diversity and novelty of venom proteins

  • Whole genome sequences of several snake species, king cobra Ophiophagus hannah (Vonk et al, 2013); Burmese python Python bivitattus (Castoe et al, 2013); rattlesnake Crotalus atrox (Dowell et al, 2016); Florida pygmy rattlesnake Sistrurus miliarius barbouri (Vicoso et al, 2013); garter snake Thamnophis elegans (Vicoso et al, 2013); five-pacer viper Deinagkistrodon acutus (Yin et al, 2016); pit viper Protobothops mucrosquamatus (NCBI Accession PRJDB4386); and corn snake Pantherophis guttatus (Ullate-Agote, Milinkovitch & Tzika, 2014) have either been published or their sequence been made available in the public domain

  • We explored the possibility of getting putative toxin gene homolog information from skin-derived low-coverage whole-genome sequencing data from Russell’s viper, and performed comparative analysis versus major toxin proteins from a previously studied report (Sharma et al, 2015)

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Summary

Introduction

Snake venom genes and their products offer an excellent model system to study gene duplication, evolution of regulatory DNA sequences, and biochemical diversity and novelty of venom proteins. Previous studies have highlighted the importance of gene duplications and/or sub-functionalization (Hargreaves et al, 2014; Malhotra et al, 2015; Rokyta et al, 2011) and transcriptional/posttranscriptional mechanisms (Casewell et al, 2014) contributing towards snake venom. Out of the sequenced genomes, only a few have been annotated, or made public, a key requirement for comparative analysis of genes. This, along with the lack of availability of whole genome sequences and/or complete transcript sequences from venom glands for most snakes has limited studies on toxin gene orthologies and gene variation among venomous snakes

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