Expression of Venom Gene Homologs in Diverse Python Tissues Suggests a New Model for the Evolution of Snake Venom

Abstract

Snake venom gene evolution has been studied intensively over the past several decades, yet most previous studies have lacked the context of complete snake genomes and the full context of gene expression across diverse snake tissues. We took a novel approach to studying snake venom evolution by leveraging the complete genome of the Burmese python, including information from tissue-specific patterns of gene expression. We identified the orthologs of snake venom genes in the python genome, and conducted detailed analysis of gene expression of these venom homologs to identify patterns that differ between snake venom gene families and all other genes. We found that venom gene homologs in the python are expressed in many different tissues outside of oral glands, which illustrates the pitfalls of using transcriptomic data alone to define "venom toxins." We hypothesize that the python may represent an ancestral state prior to major venom development, which is supported by our finding that the expansion of venom gene families is largely restricted to highly venomous caenophidian snakes. Therefore, the python provides insight into biases in which genes were recruited for snake venom systems. Python venom homologs are generally expressed at lower levels, have higher variance among tissues, and are expressed in fewer organs compared with all other python genes. We propose a model for the evolution of snake venoms in which venom genes are recruited preferentially from genes with particular expression profile characteristics, which facilitate a nearly neutral transition toward specialized venom system expression.

Proteotranscriptomic Analysis and Discovery of the Profile and Diversity of Toxin-like Proteins in Centipede

“…We finally provide an overview of toxin production from the torso to the venom gland, initially highlighting the extensive and surprising phenomenon of the toxin-like protein gene recruitment process in centipede. This result provided foundational evidence supporting the gene recruitment hypothesis for venom toxin in which toxin gene recruitment is linked to the functional constraints of the recruited proteins (24)(25)(26).…”

“…Actually, researchers have hypothesized that toxin genes display a recruitment process in snake venom (24,25). Venom gene homologs in snakes were recently shown to be expressed in many different tissues outside of the oral glands (26,36). Compared with venom gland-specific expression putative toxins, most neurotoxins and ion channel inhibitors from centipede displayed extraordinarily higher levels of expression in venoms than in torso tissues.…”

The Mobilome of Reptiles: Evolution, Structure, and Function

“…Squamate reptiles provide many classic models of extreme adaptation, e.g., the remarkable growth and metabolic shifts observed in pythons , multiple systems of venom evolution [Reyes-Velasco et al, 2015], repeated parallel instances of limb [Brandley et al, 2008] and sensory organ loss, and the remarkable adaptive radiations and convergent evolution documented in anole lizards, one of the most studied model systems in evolutionary biology [Losos, 2009]. Despite these fascinating aspects of squamate biology and their obvious utility as a research tool, only a limited number of highquality squamate genome assemblies are available and have been analyzed for their repeat content.…”

A Critique of the Toxicoferan Hypothesis

“…However, the downside of these qualities is that it has also avoided scrutiny and testing. There have recently been several studies which have cast doubt on the Toxicofera hypothesis (Hargreaves et al 2014a;Reyes-Velasco et al 2015), although their interpretation has led to alternative conclusions. Several phylogenetic analyses incorporating non-venom gland transcriptomic data have shown that non-toxin sequences nest within clades of toxin genes, and it has been acknowledged that such findings provide ".…”