{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T05:47:33Z","timestamp":1788587253230,"version":"build-2803163510"},"reference-count":150,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T00:00:00Z","timestamp":1641513600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T00:00:00Z","timestamp":1641513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"crossref","award":["DP190100304 DP210102406"],"award-info":[{"award-number":["DP190100304 DP210102406"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Biol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>The explosive radiation\u00a0and diversification of the\u00a0advanced snakes (superfamily Colubroidea) was associated with changes in all aspects of the shared\u00a0venom system. Morphological changes included the partitioning of the\u00a0mixed ancestral glands into\u00a0two discrete glands devoted for production of venom or mucous\u00a0respectively, as well as changes in\u00a0the location,\u00a0size and structural elements of the venom-delivering teeth. Evidence also exists for homology among venom gland toxins expressed across the advanced snakes. However, despite the evolutionary novelty of snake venoms, in-depth\u00a0toxin molecular evolutionary history reconstructions have been mostly limited to those\u00a0types present in only two\u00a0front-fanged snake families, Elapidae and Viperidae. To have a broader understanding of toxins shared among extant snakes, here we first sequenced the transcriptomes of eight taxonomically diverse rear-fanged species and four key viperid species and analysed\u00a0major toxin types shared across the\u00a0advanced snakes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Transcriptomes were constructed for the following families and species: Colubridae - <jats:italic>Helicops leopardinus<\/jats:italic>, <jats:italic>Heterodon nasicus<\/jats:italic>, <jats:italic>Rhabdophis subminiatus<\/jats:italic>; Homalopsidae \u2013 <jats:italic>Homalopsis buccata<\/jats:italic>; Lamprophiidae - <jats:italic>Malpolon monspessulanus<\/jats:italic>, <jats:italic>Psammophis schokari<\/jats:italic>, <jats:italic>Psammophis subtaeniatus<\/jats:italic>, <jats:italic>Rhamphiophis oxyrhynchus<\/jats:italic>; and Viperidae \u2013 <jats:italic>Bitis atropos<\/jats:italic>, <jats:italic>Pseudocerastes urarachnoides<\/jats:italic>, <jats:italic>Tropidolaeumus subannulatus<\/jats:italic>, <jats:italic>Vipera transcaucasiana<\/jats:italic>. These sequences were combined with those from available databases of other species in order to facilitate a robust reconstruction of the molecular evolutionary history of the key toxin classes present in the venom of the last common ancestor of the advanced snakes, and thus present across the full diversity of colubroid snake venoms. In addition to differential rates of evolution in toxin classes between the snake lineages, these analyses revealed multiple instances of previously unknown instances of structural and functional convergences. Structural convergences included: the evolution of new cysteines to form heteromeric complexes, such as within kunitz peptides (the beta-bungarotoxin trait evolving on at least two occasions) and within SVMP enzymes (the P-IIId trait evolving on at least three occasions); and the C-terminal tail evolving on two separate occasions within the C-type natriuretic peptides, to create structural and functional analogues of the ANP\/BNP tailed condition. Also shown was that the <jats:italic>de novo<\/jats:italic> evolution of new post-translationally liberated toxin families within the natriuretic peptide gene propeptide region occurred on at least five occasions, with novel functions ranging from induction of hypotension to post-synaptic neurotoxicity. Functional convergences included the following: multiple occasions of SVMP neofunctionalised\u00a0in procoagulant venoms into activators of the clotting factors prothrombin and Factor X; multiple instances\u00a0in procoagulant venoms where kunitz\u00a0peptides\u00a0were neofunctionalised into inhibitors of the clot destroying enzyme plasmin, thereby prolonging the half-life of the clots formed by the clotting activating enzymatic toxins; and multiple occasions of kunitz peptides neofunctionalised into neurotoxins acting on presynaptic targets, including twice just within <jats:italic>Bungarus<\/jats:italic> venoms.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>We found novel convergences in both structural and functional evolution of snake toxins. These results provide a detailed roadmap for future work to elucidate predator\u2013prey evolutionary arms races, ascertain differential clinical pathologies,\u00a0as well as documenting rich biodiscovery resources for lead compounds in the drug design and discovery pipeline.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12915-021-01208-9","type":"journal-article","created":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T19:02:48Z","timestamp":1641582168000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Dynamic genetic differentiation drives the widespread structural and functional convergent evolution of snake venom proteinaceous toxins"],"prefix":"10.1186","volume":"20","author":[{"given":"Bing","family":"Xie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Dashevsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darin","family":"Rokyta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parviz","family":"Ghezellou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Behzad","family":"Fathinia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael K.","family":"Richardson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6661-1283","authenticated-orcid":false,"given":"Bryan G.","family":"Fry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,7]]},"reference":[{"key":"1208_CR1","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1038\/nature04328","volume":"439","author":"BG Fry","year":"2006","unstructured":"Fry BG, Vidal N, Norman JA, Vonk FJ, Scheib H, Ramjan SFR, et al. 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