Snakes on a plain: biotic and abiotic factors determine venom compositional variation in a wide-ranging generalist rattlesnake

Abstract

Background Snake venoms are trophic adaptations that represent an ideal model to examine the evolutionary factors that shape polymorphic traits under strong natural selection. Venom compositional variation is substantial within and among venomous snake species. However, the forces shaping this phenotypic complexity, as well as the potential integrated roles of biotic and abiotic factors, have received little attention. Here, we investigate geographic variation in venom composition in a wide-ranging rattlesnake (Crotalus viridis viridis) and contextualize this variation by investigating dietary, phylogenetic, and environmental variables that covary with venom. Results Using shotgun proteomics, venom biochemical profiling, and lethality assays, we identify 2 distinct divergent phenotypes that characterize major axes of venom variation in this species: a myotoxin-rich phenotype and a snake venom metalloprotease (SVMP)-rich phenotype. We find that dietary availability and temperature-related abiotic factors are correlated with geographic trends in venom composition. Conclusions Our findings highlight the potential for snake venoms to vary extensively within species, for this variation to be driven by biotic and abiotic factors, and for the importance of integrating biotic and abiotic variation for understanding complex trait evolution. Links between venom variation and variation in biotic and abiotic factors indicate that venom variation likely results from substantial geographic variation in selection regimes that determine the efficacy of venom phenotypes across populations and snake species. Our results highlight the cascading influence of abiotic factors on biotic factors that ultimately shape venom phenotype, providing evidence for a central role of local selection as a key driver of venom variation.

Studying Venom Toxin Variation Using Accurate Masses from Liquid Chromatography–Mass Spectrometry Coupled with Bioinformatic Tools

“…While venom variation between species has been well studied (e.g., [ 4 , 5 , 10 , 11 ]), the extent of intraspecific variation is starting to gain significant attention [ 12 ]. A thorough understanding of venom variation is of interest to different scientific disciplines, as venom variation provides a model system for understanding adaptive responses to biotic and abiotic factors in an ecological context [ 5 , 7 , 13 , 14 ]. Additionally, snakebite envenoming is a neglected tropical disease severely affecting millions of people worldwide [ 15 ], and venom variation between and within species can complicate the cross-neutralising capacity of snakebite treatments [ 16 ].…”

Venom diversity in Naja mossambica: Insights from proteomic and immunochemical analyses reveal intraspecific differences

“…Venom diversity plays a crucial role in determining the clinical manifestations of snakebite envenoming. Variations in venom composition have been extensively documented not only between different snake species but also, more recently, within a single species [ 5 – 11 ]. Hence, intraspecific differences in venom composition have emerged as an important area of study, highlighting the complex nature of venom.…”

“…Hence, intraspecific differences in venom composition have emerged as an important area of study, highlighting the complex nature of venom. Factors such as geographic location, diet, genetic variation, and evolutionary adaptations can contribute to these variations [ 2 , 11 – 12 ]. Gaining a comprehensive understanding of these intraspecific differences is essential for developing effective snakebite management strategies and targeted antivenom therapies, as they directly impact the diverse clinical effects observed in envenomed patients [ 2 , 12 ].…”

Venom diversity inNaja mossambica: Insights from proteomic and immunochemical analyses reveal intraspecific differences

“…Venom diversity plays a crucial role in determining the clinical manifestations of snakebite envenoming. Variations in venom composition have been extensively documented not only between different snake species but also, more recently, within a single species [5][6][7][8][9][10][11]. Hence, intraspecific differences in venom composition have emerged as an important area of study, highlighting the complex nature of venom.…”

“…Hence, intraspecific differences in venom composition have emerged as an important area of study, highlighting the complex nature of venom. Factors such as geographic location, diet, genetic variation, and evolutionary adaptations can contribute to these variations [2,[11][12]. Gaining a comprehensive understanding of these intraspecific differences is essential for developing effective snakebite management strategies and targeted antivenom therapies, as they directly impact the diverse clinical effects observed in envenomed patients [2,12].…”