Modern venomics--Current insights, novel methods, and future perspectives in biological and applied animal venom research

Venoms have evolved >100 times in all major animal groups, and their components, known as toxins, have been fine-tuned over millions of years into highly effective biochemical weapons. There are many outstanding questions on the evolution of toxin arsenals, such as how venom genes originate, how venom contributes to the fitness of venomous species, and which modifications at the genomic, transcriptomic, and protein level drive their evolution. These questions have received particularly little attention outside of snakes, cone snails, spiders, and scorpions. Venom compounds have further become a source of inspiration for translational research using their diverse bioactivities for various applications. We highlight here recent advances and new strategies in modern venomics and discuss how recent technological innovations and multi-omic methods dramatically improve research on venomous animals. The study of genomes and their modifications through CRISPR and knockdown technologies will increase our understanding of how toxins evolve and which functions they have in the different ontogenetic stages during the development of venomous animals. Mass spectrometry imaging combined with spatial transcriptomics, in situ hybridization techniques, and modern computer tomography gives us further insights into the spatial distribution of toxins in the venom system and the function of the venom apparatus. All these evolutionary and biological insights contribute to more efficiently identify venom compounds, which can then be synthesized or produced in adapted expression systems to test their bioactivity. Finally, we critically discuss recent agrochemical, pharmaceutical, therapeutic, and diagnostic (so-called translational) aspects of venoms from which humans benefit.This work is funded by the European Cooperation in Science and Technology (COST, www.cost.eu) and based upon work from the COST Action CA19144 – European Venom Network (EUVEN, see https://euven-network.eu/). This review is an outcome of EUVEN Working Group 2 (“Best practices and innovative tools in venomics”) led by B.M.v.R. As coordinator of the group Animal Venomics until end 2021 at the Institute for Insectbiotechnology, JLU Giessen, B.M.v.R. acknowledges the Centre for Translational Biodiversity Genomics (LOEWE-TBG) in the programme “LOEWE – Landes-Offensive zur Entwicklung Wissenschaftlich-ökonomischer Exzellenz” of Hesse's Ministry of Higher Education, Research, and the Arts. B.M.v.R. and I.K. further acknowledge funding on venom research by the German Science Foundation to B.M.v.R. (DFG RE3454/6-1). A.C., A.V., and G.Z. were supported by the European Union's Horizon 2020 Research and Innovation program through Marie Sklodowska-Curie Individual Fellowships (grant agreements No. A.C.: 896849, A.V.: 841576, and G.Z.: 845674). M.P.I. is supported by the TALENTO Program by the Regional Madrid Government (2018-T1/BIO-11262). T.H.'s venom research is funded by the DFG projects 271522021 and 413120531. L.E. was supported by grant No. 7017-00288 from the Danish Council for Independent Research (Technology and Production Sciences). N.I. acknowledges funding on venom research by the Research Fund of Nevsehir Haci Bektas Veli University (project Nos. ABAP20F28, BAP18F26). M.I.K. and A.P. acknowledge support from GSRT National Research Infrastructure structural funding project INSPIRED (MIS 5002550). G.A. acknowledges support from the Slovenian Research Agency grants P1-0391, J4-8225, and J4-2547. G.G. acknowledges support from the Institute for Medical Research and Occupational Health, Zagreb, Croatia. E.A.B.U. is supported by a Norwegian Research Council FRIPRO-YRT Fellowship No. 287462

A Phylogenomic Approach to Resolve the Arthropod Tree of Life

Arthropods were the first animals to conquer land and air. They encompass more than three quarters of all described living species. This extraordinary evolutionary success is based on an astoundingly wide array of highly adaptive body organizations. A lack of robustly resolved phylogenetic relationships, however, currently impedes the reliable reconstruction of the underlying evolutionary processes. Here, we show that phylogenomic data can substantially advance our understanding of arthropod evolution and resolve several conflicts among existing hypotheses. We assembled a data set of 233 taxa and 775 genes from which an optimally informative data set of 117 taxa and 129 genes was finally selected using new heuristics and compared with the unreduced data set. We included novel expressed sequence tag (EST) data for 11 species and all published phylogenomic data augmented by recently published EST data on taxonomically important arthropod taxa. This thorough sampling reduces the chance of obtaining spurious results due to stochastic effects of undersampling taxa and genes. Orthology prediction of genes, alignment masking tools, and selection of most informative genes due to a balanced taxa-gene ratio using new heuristics were established. Our optimized data set robustly resolves major arthropod relationships. We received strong support for a sister group relationship of onychophorans and euarthropods and strong support for a close association of tardigrades and cycloneuralia. Within pancrustaceans, our analyses yielded paraphyletic crustaceans and monophyletic hexapods and robustly resolved monophyletic endopterygote insects. However, our analyses also showed for few deep splits that were recently thought to be resolved, for example, the position of myriapods, a remarkable sensitivity to methods of analyses