{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T13:23:04Z","timestamp":1791724984291,"version":"4.3.4"},"reference-count":66,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,25]],"date-time":"2022-03-25T00:00:00Z","timestamp":1648166400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2018\/26520-4"],"award-info":[{"award-number":["2018\/26520-4"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2016\/50127-5"],"award-info":[{"award-number":["2016\/50127-5"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2013\/07467-1"],"award-info":[{"award-number":["2013\/07467-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Interspecific differences in snake venom compositions can result from distinct regulatory mechanisms acting in each species. However, comparative analyses focusing on identifying regulatory elements and patterns that led to distinct venom composition are still scarce. Among venomous snakes, Bothrops cotiara and Bothrops fonsecai represent ideal models to complement our understanding of the regulatory mechanisms of venom production. These recently diverged species share a similar specialized diet, habitat, and natural history, but each presents a distinct venom phenotype. Here, we integrated data from the venom gland transcriptome and miRNome and the venom proteome of B. fonsecai and B. cotiara to better understand the regulatory mechanisms that may be acting to produce differing venom compositions. We detected not only the presence of similar toxin isoforms in both species but also distinct expression profiles of phospholipases A2 (PLA2) and some snake venom metalloproteinases (SVMPs) and snake venom serine proteinases (SVSPs) isoforms. We found evidence of modular expression regulation of several toxin isoforms implicated in venom divergence and observed correlated expression of several transcription factors. We did not find strong evidence for miRNAs shaping interspecific divergence of the venom phenotypes, but we identified a subset of toxin isoforms whose final expression may be fine-tuned by specific miRNAs. Sequence analysis on orthologous toxins showed a high rate of substitutions between PLA2s, which indicates that these toxins may be under strong positive selection or represent paralogous toxins in these species. Our results support other recent studies in suggesting that gene regulation is a principal mode of venom evolution across recent timescales, especially among species with conserved ecotypes.<\/jats:p>","DOI":"10.3390\/toxins14040237","type":"journal-article","created":{"date-parts":[[2022,3,27]],"date-time":"2022-03-27T21:31:25Z","timestamp":1648416685000},"page":"237","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Differences in PLA2 Constitution Distinguish the Venom of Two Endemic Brazilian Mountain Lanceheads, Bothrops cotiara and Bothrops fonsecai"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3196-0173","authenticated-orcid":false,"given":"Pedro G.","family":"Nachtigall","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Toxinologia Aplicada, Center of Toxins, Immune-Response and Cell Signaling (CeTICS), Instituto Butantan, S\u00e3o Paulo, SP 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana A.","family":"Freitas-de-Sousa","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunopatologia, Instituto Butantan, S\u00e3o Paulo, SP 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0297-1313","authenticated-orcid":false,"given":"Andrew J.","family":"Mason","sequence":"additional","affiliation":[{"name":"Department of Evolution, Ecology, and Organismal Biology, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1787-6634","authenticated-orcid":false,"given":"Ana M.","family":"Moura-da-Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Imunopatologia, Instituto Butantan, S\u00e3o Paulo, SP 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9896-9722","authenticated-orcid":false,"given":"Felipe G.","family":"Grazziotin","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Cole\u00e7\u00f5es Zool\u00f3gicas, Instituto Butantan, S\u00e3o Paulo, SP 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00e1cio L. M.","family":"Junqueira-de-Azevedo","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Toxinologia Aplicada, Center of Toxins, Immune-Response and Cell Signaling (CeTICS), Instituto Butantan, S\u00e3o Paulo, SP 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Greene, H.W. (1997). Snakes: The Evolution of Mystery in Nature, University of California Press.","DOI":"10.1525\/9780520935433"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Grundler, M.C., and Rabosky, D.L. (2021). Rapid increase in snake dietary diversity and complexity following the end-Cretaceous mass extinction. 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