Venoms to the rescue

Holford, Mandë; Daly, Marymegan; King, Glenn F.; Norton, Raymond S.

doi:10.1126/science.aau7761

Cited by 77 publications

(82 citation statements)

References 15 publications

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“…The acquisition of venoms and poisons is a transformative event in the evolution of an animal, because it remodels the predator-prey interaction from a physical to a biochemical battle, enabling animals to prey on, and defend themselves against, much larger animals (Holford, Daly, King, & Norton, 2018). Here we report the initial functional and structural characterization of PmPV2, a toxin that, according to the experimental results on mice and cell cultures, would be a potential defense of apple snail embryos against predation.…”

Section: Discussionmentioning

confidence: 99%

Exaptation of two ancient immune proteins into a new dimeric pore-forming toxin in snails

Giglio

Ituarte

Milesi

et al. 2019

Preprint

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The Membrane Attack Complex-Perforin (MACPF) family is ubiquitously found in all kingdoms. They have diverse cellular roles but MACPF but pore-forming toxic function are very rare in animals. Here we present the structure of PmPV2, a MACPF toxin from the poisonous apple snail eggs, that can affect the digestive and nervous systems of potential predators. We report the three-dimensional structure of PmPV2, at 15 Å resolution determined by negative stain electron microscopy (NS-EM) and its solution structure by small angle X-ray scattering (SAXS). We found that PV2s differ from nearly all MACPFs in two respects: it is a dimer in solution and protomers combine two immune proteins into an AB toxin. MACPF chain is linked by a single disulfide bond to a tachylectin chain, and two heterodimers are arranged head-to-tail by non-covalent forces in the native protein. MACPF domain is fused with a putative new Ct-accessory domain exclusive to invertebrates. Tachylectin is a six-bladed β-propeller, similar to animal tectonins. We experimentally validated the predicted functions of both subunits and demonstrated for the first time that PV2s are true pore-forming toxins. The tachylectin ..B.. delivery subunit would bind to target membranes, and then its MACPF ..A.. toxic subunit disrupt lipid bilayers forming large pores altering the plasma membrane conductance. These results indicate that PV2s toxicity evolved by linking two immune proteins where their combined preexisting functions give rise to a new toxic entity with a novel role in defense against predation. This structure is an unparalleled example of protein exaptation.

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Section: Discussionmentioning

confidence: 99%

Exaptation of two ancient immune proteins into a new dimeric pore-forming toxin in snails

Giglio

Ituarte

Milesi

et al. 2019

Preprint

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“…They are used for defense, predation or competitor deterrence, but in all cases they are physiologically expensive traits that have been optimized by strong selective pressure for specific functions. This evolutionary streamlining often results in high selectivity and target-specific bioactivity, meaning that animal venoms are now considered valuable bioresources in the field of drug discovery (Holford et al, 2018). Several blockbuster drugs have been derived from venom components (Holford et al, 2018), but they were also investigated as research tools, cosmetics, industrial enzymes or bioinsecticides (e.g.…”

Section: Introductionmentioning

confidence: 99%

“…This evolutionary streamlining often results in high selectivity and target-specific bioactivity, meaning that animal venoms are now considered valuable bioresources in the field of drug discovery (Holford et al, 2018). Several blockbuster drugs have been derived from venom components (Holford et al, 2018), but they were also investigated as research tools, cosmetics, industrial enzymes or bioinsecticides (e.g. Duterte and Lewis, 2010;Pennington et al, 2018;Dongol et al, 2019;Saez and Herzig, 2019).…”

Section: Introductionmentioning

confidence: 99%

An economic dilemma between weapon systems may explain an arachno-atypical venom in wasp spiders (Argiope bruennichi)

Lueddecke

Reumont

Foerster

et al. 2020

Preprint

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Spiders use venom to subdue their prey, but little is known about the diversity of venoms in different spider families. Given the limited data available for orb-weaver spiders (Araneidae) we selected the wasp spider Argiope bruennichi for detailed analysis. Our strategy combined a transcriptomics pipeline based on multiple assemblies with a dual proteomics workflow involving parallel mass spectrometry techniques and electrophoretic profiling. We found that the remarkably simple venom of A. bruennichi has an atypical composition compared to other spider venoms, prominently featuring members of the CAP superfamily and other, mostly high-molecular-weight proteins. We also detected a subset of potentially novel toxins similar to neuropeptides. We discuss the potential function of these proteins in the context of the unique hunting behavior of wasp spiders, which rely mostly on silk to trap their prey. We propose that the simplicity of the venom evolved to solve an economic dilemma between two competing yet metabolically expensive weapon systems. This study emphasizes the importance of cutting-edge methods to encompass smaller lineages of venomous species that have yet to be characterized in detail, allowing us to understand the biology of their venom systems and to mine this prolific resource for translational research.

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“…Venomous species are extremely diverse and ubiquitously evolved in all known animal phyla, as for example in old lineages such as marine cnidarians, molluscs, or polychaetes, but also terrestrial groups like reptiles, all major arthropod clades and even mammals Dutertre et al, 2014;von Reumont et al, 2014a,b). It is estimated that around 200,000 animal species (Holford et al, 2018) use venom as the utmost important molecular trait that guarantees the fitness and survival of species being employed for defense, predation, and competition von Reumont et al, 2014a;Sunagar et al, 2016), see also Figure 1. In contrast to poisons, which are generally composed of less complex mixtures of toxic substances and used in a rather unspecific manner, venoms are constituted by complex toxin components such as peptides, proteins, and other smaller organic molecules (Fry et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…The production of an effective antidote is largely dependent on the present knowledge of a species' venom cocktail and possible intra-specific variation in its toxin components (Chippaux et al, 1991;Gutiérrez et al, 2009). Another motivation behind many studies in venomics is to screen for and to harvest the potential of identified venom proteins (single toxins) for applied research, such as the development of highly specific agrochemicals like bio-insecticides or pharmaceutical applications and drug design (Windley et al, 2012;King and Hardy, 2013;Holford et al, 2018;Pennington et al, 2018;Senji Laxme et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

The Significance of Comparative Genomics in Modern Evolutionary Venomics

Drukewitz

Reumont

2019

Front. Ecol. Evol.

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Venoms evolved convergently in diverse animal lineages as key adaptations that increase the evolutionary fitness of species which are manifold employed for defense, predation, and competition. They constitute complex cocktails of various toxins that feature a broad range of bioactivities. The majority of described venom proteins belong to protein families that are known to comprise housekeeping genes or harbor protein-domains, which are present in genes with non-venom related functions. However, the evolutionary processes and mechanisms that foster the origin of these venom proteins and triggered their recruitment into the venom delivery system are still critically discussed. In most instances single or combined proteomic and transcriptomic approaches are applied to describe venom compositions and the biological context of venoms. For neglected species these studies represent crucial contributions to improve our understanding of venom diversity on a broader scale. Nonetheless, the inference of the evolutionary origin of putative toxins in these studies could be misleading without appropriate coverage of gene populations from different tissue samples (gene completeness) or complementary genome data. Providing a valid backbone to correctly map transcriptome and proteome data, whole genome sequences facilitate a clear distinction between variability of venom proteins or toxins due to posttranslational modifications, alternative splicing, and false-positive matches that stem from sequencing or read processing and assembly errors. High-quality whole genome sequence data of venomous species are still sparse and unevenly distributed within taxon lineages. However, to reveal the evolutionary pattern of putative toxins in venomous lineages and to identify ancestral variants of venom proteins, the appropriate sampling of genomes from venomous and non-venomous species is crucial. Nevertheless, larger comparative studies based on multiple whole genome data sets are still sparse to uncover processes of venom evolution. Here, we review the general potential of comparative genomics in venomics to unravel mechanisms and patterns of evolutionary origin of toxin genes. Finally, we discuss the benefit of whole genome data to improve transcriptomics and proteomics-only studies, in particular if datasets are applied to assess the evolutionary origin of venom proteins.

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Venoms to the rescue

Abstract: Insights into the evolutionary biology of venoms are leading to therapeutic advances

Cited by 77 publications

References 15 publications

Exaptation of two ancient immune proteins into a new dimeric pore-forming toxin in snails

Exaptation of two ancient immune proteins into a new dimeric pore-forming toxin in snails

An economic dilemma between weapon systems may explain an arachno-atypical venom in wasp spiders (Argiope bruennichi)

The Significance of Comparative Genomics in Modern Evolutionary Venomics

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