What's in a mass?

This short essay pretends to make the reader reflect on the concept of biological mass and on the added value that the determination of this molecular property of a protein brings to the interpretation of evolutionary and translational snake venomics research. Starting from the premise that the amino acid sequence is the most distinctive primary molecular characteristics of any protein, the thesis underlying the first part of this essay is that the isotopic distribution of a protein's molecular mass serves to unambiguously differentiate it from any other of an organism's proteome. In the second part of the essay, we discuss examples of collaborative projects among our laboratories, where mass profiling of snake venom PLA2 across conspecific populations played a key role revealing dispersal routes that determined the current phylogeographic pattern of the species.

Snake venomics at the crossroads between ecological and clinical toxinology

Venoms are complex secretions used for predatory and defensive purposes by a wide range of organisms. Venoms and venom production represent fascinating systems to study fundamental evolutionary processes. Understanding the evolution of venom generation demands the integration of the selective interactions and mechanisms, which transformed ordinary genes into deadly toxins, in the context of the natural history of the producing organism. Humans are not prey for any extant venomous creature on Earth, and thus human envenomings result from unexpected encounters with venomous animals, e.g., snakes. Research on snake venoms conducted on mammalian prey from an ecologically informed perspective is conceptually transferable to the clinic, highlighting the mutually enlightening relationship between evolutionary and translational venomics.

Extended snake venomics by top-down in-source decay: Investigating the newly discovered Anatolian Meadow viper subspecies, Vipera anatolica senliki

Herein we report on the venom proteome of Vipera anatolica senliki, a recently discovered and hitherto unexplored subspecies of the critically endangered Anatolian Meadow viper endemic to the Antalya Province of Turkey. Integrative venomics, including venom gland transcriptomics as well as complementary bottom-up and top-down proteomic analyses, were applied to fully characterize the venom of V. a. senliki. Furthermore, the classical top-down venomics approach was extended to elucidate the venom proteome by an alternative in-source decay (ISD) proteomics workflow using the reducing matrix 1,5-diaminonaphthalene (1,5-DAN). Top-down ISD proteomics allows for disulfide bond mapping as well as effective de novo identification of high molecular weight venom constituents, both of which are difficult to achieve by commonly established top-down approaches. Venom gland transcriptome analysis identified 42 venom transcript annotations from 13 venom toxin families. Relative quantitative snake venomics revealed snake venom metalloproteinases (svMP, 42.9%) as the most abundant protein family, followed by several less dominant toxin families. Online mass profiling and top-down venomics provide a detailed insight into the venom proteome of V. a. senliki and facilitates a comparative analysis of venom variability for the closely related subspecies, V. a. anatolica.TOC Figure