Venom Gene Sequence Diversity and Expression Jointly Shape Diet Adaptation in Pitvipers

Abstract

Understanding the joint roles of amino acid sequences variation of proteins and differential expression during adaptive evolution is a fundamental, yet largely unrealized, goal of evolutionary biology. Here, we use phylogenetic path analysis to analyze a comprehensive venom gland transcriptome dataset spanning three genera of pitvipers to identify the functional genetic basis of a key adaptation (venom complexity) linked to diet breadth. Analysis of gene family-specific patterns reveal that, for genes encoding two of the most important venom proteins (SVMPs and SVSPs), there are direct, positive relationships between sequence diversity, evenness of expression, and increased diet breadth. Further analysis of gene family diversification for these proteins showed no constraint on how individual lineages achieved toxin gene sequence diversity in terms of patterns of paralog diversification. In contrast, another major venom protein family (PLA2s) showed no relationship between venom molecular diversity and diet breadth. Additional analyses suggest that other molecular mechanisms—such as higher absolute levels of expression—are responsible for diet adaptation involving these venom proteins. Broadly, our findings argue that functional diversity generated through sequence and expression variation determine adaptation in key components of pitviper venoms, which mediate complex molecular interactions between the snakes and their prey.

Highly Evolvable: Investigating Interspecific and Intraspecific Venom Variation in Taipans (Oxyuranus spp.) and Brown Snakes (Pseudonaja spp.)

“…In Oxyuranus , fluctuations in mass abundance, i.e., shifting levels of gene expression, appear to play a more important role. In a recent study, Mason et al described the distinct but complementary roles of toxin absence/presence and variations in expression levels in generating variation in the venom phenotypes of North American pit vipers [ 48 ]. This toxin diversity was linked to the phylogenetically distinct prey taxa in their diets [ 6 , 48 ].…”

“…In a recent study, Mason et al described the distinct but complementary roles of toxin absence/presence and variations in expression levels in generating variation in the venom phenotypes of North American pit vipers [ 48 ]. This toxin diversity was linked to the phylogenetically distinct prey taxa in their diets [ 6 , 48 ]. In our case, given the degree of variation we have observed, coupled with the available data on Pseudonaja and Oxyuranus , it is not possible to tell a convincing adaptationist story that would tightly link venom variation to diverse feeding ecologies.…”

Comprehensive isoform-level analysis reveals the contribution of alternative isoforms to venom evolution and repertoire diversity

“…Additionally, alternative isoforms have been suggested to facilitate rapid evolutionary innovations ( Tovar-Corona et al 2015 ; Howes et al 2017 ; Fujikura et al 2018 ; Wright et al 2022 ). Although the rapid evolution of venom compositions in parasitoid wasps has been observed, potentially driven by variable host ranges or parasitoid strategies ( Martinson et al 2017 ; Mason et al 2022 ; Ye et al 2022 ), few studies have investigated the role of alternative isoforms in the origin of venom genes. Multiple models of venom evolution have been proposed over the years ( Mrinalini and Werren 2016 ), including duplication followed by neofunctionalization ( Chen et al 2021 ; Yang et al 2021 ; Ye et al 2022 ), co-option ( Martinson et al 2017 ; Ye et al 2022 ), and lateral gene transfer ( Martinson et al 2016 ), with three of these models well-characterized in parasitoid wasp venom systems.…”

“…Moreover, venom presents excellent opportunities for investigating the emergence of new gene functions and the evolution of novel regulatory networks. Different venomous animals have developed diverse venom genes for distinct purposes ( Casewell et al 2013 ; Reyes-Velasco et al 2015 ; Schield et al 2019 , 2022 ; Giorgianni et al 2020 ; Almeida et al 2021 ; Barua and Mikheyev 2021 ; Mason et al 2022 ; Perry et al 2022 ). Although extensive studies on venom genes have provided profound insights into venom diversity, origins, turnover, regulatory mechanisms, and biological functions, the majority of these studies have focused on the gene level ( Casewell et al 2013 ; Suryamohan et al 2020 ; Almeida et al 2021 ).…”

A novel broad spectrum venom metalloproteinase autoinhibitor in the rattlesnakeCrotalus atroxevolved via a shift in paralog function

“…The ability of prey to evolve venom resistance can trigger a coevolutionary arms race in which snake predators in turn evolve toxins or venom compositions that circumvent resistance, as has been shown, for example, in the case of California ground squirrels and the Northern Pacific rattlesnake ( C. oreganus ) ( 11 , 13 ). Indeed, it is widely thought that the diversity of snake venom composition reflects adaptation to the diversity and susceptibility of prey in their diets ( 14 , 15 , 16 , 17 ).…”