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Found throughout various tropical and temperate habitats, these predatory arachnids have a long evolutionary history, with a fossil record that began in the Silurian. While all scorpions are venomous, the asymmetrically diverse family Buthidae harbors nearly half the diversity of extant scorpions, and all but one of the 58 species that are medically significant to humans. However, the lack of a densely sampled scorpion phylogeny has hindered broader inferences of the diversification dynamics of scorpion toxins. To redress this gap, we assembled a phylogenomic data set of 100 scorpion venom gland transcriptomes and genomes, emphasizing the sampling of highly toxic buthid genera. To infer divergence times of venom gene families, we applied a phylogenomic node dating approach for the species tree in tandem with phylostratigraphic bracketing to estimate the minimum ages of mammal-specific toxins. Our analyses establish a robustly supported phylogeny of scorpions, particularly with regard to relationships between medically significant taxa. Analysis of venom gene families shows that mammal-active sodium channel toxins (NaTx) have independently evolved in five lineages within Buthidae. Temporal windows of mammal-targeting toxin origins are correlated with the basal diversification of major scorpion mammal predators such as shrews, bats, and rodents. These results suggest an evolutionary model of relatively recent diversification of buthid NaTx homologs in response to the diversification of scorpion predators. [Adaptation; arachnids; phylogenomic dating; phylostratigraphy; venom.]<\/jats:p>","DOI":"10.1093\/sysbio\/syac021","type":"journal-article","created":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T20:12:00Z","timestamp":1646770320000},"page":"1281-1289","source":"Crossref","is-referenced-by-count":61,"title":["Phylogenomics of Scorpions Reveal Contemporaneous Diversification of Scorpion Mammalian Predators and Mammal-Active Sodium Channel Toxins"],"prefix":"10.1093","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6062-282X","authenticated-orcid":false,"given":"Carlos E","family":"Santib\u00e1\u00f1ez-L\u00f3pez","sequence":"first","affiliation":[{"name":"Department of Integrative Biology, University of Wisconsin\u2013Madison , Madison, WI 53706, USA"},{"name":"Department of Biology, Western Connecticut State University , 181 White Street, Danbury, CT 06810, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3862-2756","authenticated-orcid":false,"given":"Shlomi","family":"Aharon","sequence":"additional","affiliation":[{"name":"National Natural History Collections, The Hebrew University of Jerusalem , 91904 Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2315-2368","authenticated-orcid":false,"given":"Jes\u00fas A","family":"Ballesteros","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology, University of Wisconsin\u2013Madison , Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9040-4863","authenticated-orcid":false,"given":"Guilherme","family":"Gainett","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology, University of Wisconsin\u2013Madison , Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9782-4959","authenticated-orcid":false,"given":"Caitlin M","family":"Baker","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology, University of Wisconsin\u2013Madison , Madison, WI 53706, USA"},{"name":"Department of Organismic and Evolutionary Biology, Harvard University , Cambridge, MA 02138, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1340-068X","authenticated-orcid":false,"given":"Edmundo","family":"Gonz\u00e1lez-Santill\u00e1n","sequence":"additional","affiliation":[{"name":"Colecci\u00f3n Nacional de Ar\u00e1cnidos, Instituto de Biolog\u00eda , Universidad Nacional Aut\u00f3noma de M\u00e9xico, 3er Circuito s\/n Ciudad Universitaria, Alcald\u00eda Coyoac\u00e1n, C.P. 04510 Mexico city, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1482-0109","authenticated-orcid":false,"given":"Mark S","family":"Harvey","sequence":"additional","affiliation":[{"name":"Department of Terrestrial Zoology, Western Australian Museum, Locked Bag 49 , Welshpool DC 6986, Western Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3345-4642","authenticated-orcid":false,"given":"Mohamed K","family":"Hassan","sequence":"additional","affiliation":[{"name":"Zoology Department, Faculty of Science, Port Said University , Port Fouad, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9056-0228","authenticated-orcid":false,"given":"Ali Hussein","family":"Abu Almaaty","sequence":"additional","affiliation":[{"name":"Zoology Department, Faculty of Science, Port Said University , Port Fouad, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0413-7675","authenticated-orcid":false,"given":"Shorouk Mohamed","family":"Aldeyarbi","sequence":"additional","affiliation":[{"name":"Zoology Department, Faculty of Science, Port Said University , Port Fouad, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0839-760X","authenticated-orcid":false,"given":"Lionel","family":"Monod","sequence":"additional","affiliation":[{"name":"De\u00edpartement des arthropodes et d\u2019entomologie I , Muse\u00edum d\u2019histoire naturelle, Route de Malagnou 1, 1208 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1093-5822","authenticated-orcid":false,"given":"Andr\u00e9s","family":"Ojanguren-Affilastro","sequence":"additional","affiliation":[{"name":"Divisi\u00f3n Arachnolog\u00eda, Museo Argentino de Ciencias Naturales , Av. 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