Venoms are one of the most convergent of animal traits known, and encompass a much greater taxonomic and functional diversity than is commonly appreciated. This knowledge gap limits the potential of venom as a model trait in evolutionary biology. Here, we summarize the taxonomic and functional diversity of animal venoms and relate this to what is known about venom system morphology, venom modulation, and venom pharmacology, with the aim of drawing attention to the importance of these largely neglected aspects of venom research. We find that animals have evolved venoms at least 101 independent times and that venoms play at least 11 distinct ecological roles in addition to predation, defense, and feeding. Comparisons of different venom systems suggest that morphology strongly influences how venoms achieve these functions, and hence is an important consideration for understanding the molecular evolution of venoms and their toxins. Our findings also highlight the need for more holistic studies of venom systems and the toxins they contain. Greater knowledge of behavior, morphology, and ecologically relevant toxin pharmacology will improve our understanding of the evolution of venoms and their toxins, and likely facilitate exploration of their potential as sources of molecular tools and therapeutic and agrochemical lead compounds.

Voltage-gated sodium (Na_V) channels are critical regulators of neuronal excitability and are targeted by many toxins that directly interact with the pore-forming α subunit, typically via extracellular loops of the voltage-sensing domains, or residues forming part of the pore domain. Excelsatoxin A (ExTxA), a pain-causing knottin peptide from the Australian stinging tree Dendrocnide excelsa, is the first reported plant-derived Na_V channel modulating peptide toxin. Here we show that TMEM233, a member of the dispanin family of transmembrane proteins expressed in sensory neurons, is essential for pharmacological activity of ExTxA at Na_V channels, and that co-expression of TMEM233 modulates the gating properties of Na_V1.7. These findings identify TMEM233 as a previously unknown Na_V1.7-interacting protein, position TMEM233 and the dispanins as accessory proteins that are indispensable for toxin-mediated effects on Na_V channel gating, and provide important insights into the function of Na_V channels in sensory neurons.

Agricultural ecosystems have faced dramatic changes during past decades, resulting in a dramatic loss of farmland biodiversity. The Corn Bunting Emberiza calandra is considered a suitable indicator for the conservation value of farmland habitats, and has recently suffered strong declines throughout much of its European range. As a basis for targeted conservation measures, we investigated the habitat preferences of this species in north-eastern Germany by comparing the composition of male territories with randomly chosen control sites. A territory was defined as the area within a radius of 150 meters around the assumed centre of the territory, as the majority of nests is found within this radius. To assess food availability for nestlings, arthropod abundance within the most abundant land use types i.e. crop fields, fallows, grassland as well as within unploughed strips was investigated. In total we found 102 male Corn Bunting territories, which were mainly composed of crop fields (50%), grassland (28%), and fallows (12%). Territories compared with control sites were characterized by a lower proportion of crop fields, a higher proportion of fallows, more diverse land use types, more abundant field boundaries, unploughed strips, and tracks, and a higher availability of song posts. However, neither the number of larger (≥ 1 cm), smaller (< 1 cm) or all arthropods differed significantly among analysed land use types i.e. crop fields, fallows, grassland, unploughed strips. Our study confirms the significance of habitat heterogeneity and especially of sites with sparse vegetation (fallows > 10%) and song posts (> 70 m ‘linear song posts’ or > 1 solitary post per ha) for the habitat selection of male Corn Buntings. We conclude that measures to halt population declines of Corn Buntings seem to be relatively easy to implement, provided that farmers are granted a fair compensation.

In the context of evolutionary arthopodial transformations, centipede ultimate legs exhibit a plethora of morphological modifications and behavioral adaptations. Many species possess significantly elongated, thickened, or pincer-like ultimate legs. They are frequently sexually dimorphic, indicating a role in courtship and mating. In addition, glandular pores occur more commonly on ultimate legs than on walking legs, indicating a role in secretion, chemical communication, or predator avoidance. In this framework, this study characterizes the evolutionarily transformed ultimate legs in Lithobius forficatus in comparison with regular walking legs. A comparative analysis using macro-photography, SEM, μCT, autofluorescence, backfilling, and 3D-reconstruction illustrates that ultimate legs largely resemble walking legs, but also feature a series of distinctions. Substantial differences are found with regard to aspects of the configuration of specific podomeres, musculature, abundance of epidermal glands, typology and distribution of epidermal sensilla, and architecture of associated nervous system structures. In consideration of morphological and behavioral characteristics, ultimate legs in L. forficatus primarily serve a defensive, but also a sensory function. Moreover, morphologically coherent characteristics in the organization of the ultimate leg versus the antenna-associated neuromere point to constructional constraints in the evolution of primary processing neuropils.

Harvester ants (genus Pogonomyrmex) are renowned for their stings which cause intense, long-lasting pain and other neurotoxic symptoms in vertebrates. Here we show that harvester ant venoms are relatively simple and composed largely of peptide toxins. One class of peptides is primarily responsible for the long-lasting local pain of envenomation via activation of peripheral sensory neurons. These hydrophobic, cysteine-free peptides potently modulate mammalian voltage-gated sodium (Na_V) channels, reducing the voltage threshold for activation and inhibiting channel inactivation. These toxins appear to have evolved specifically to deter vertebrates.

In light of competing hypotheses on arthropod phylogeny, independent data are needed in addition to traditional morphology and modern molecular approaches. One promising approach involves comparisons of structure and development of the nervous system. In addition to arthropod brain and ventral nerve cord morphology and anatomy, individually identifiable neurons (IINs) provide new character sets for comparative neurophylogenetic analyses. However, very few species and transmitter systems have been investigated, and still fewer species of centipedes have been included in such analyses. In a multi-methodological approach, we analyze the ventral nerve cord of the centipede Lithobius forficatus using classical histology, X-ray micro-computed tomography and immunohistochemical experiments, combined with confocal laser-scanning microscopy to characterize walking leg ganglia and identify IINs using various neurotransmitters. In addition to the subesophageal ganglion, the ventral nerve cord of L. forficatus is composed of the forcipular ganglion, 15 well-separated walking leg ganglia, each associated with eight pairs of nerves, and the fused terminal ganglion. Within the medially fused hemiganglia, distinct neuropilar condensations are located in the ventral-most domain. Immunoreactive neurons of different transmitter systems (allatostatin, histamine, and FMRF-amide) display serially homologous patterns that may lay the foundation for comparison with other arthropod taxa. Moreover, a pair of histaminergic neurons may constitute a promising intra- as well as interspecific IIN candidate.