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Several isoforms present in these venoms can be structurally classified in two groups. Class I Sphingomyelinase D contains a single disulphide bridge and variable loop. Class II Sphingomyelinase D presents an additional intrachain disulphide bridge that links a flexible loop with a catalytic loop. These classes exhibit differences in their toxic potential. In this paper we address the distribution of the structural classes of SMase D within and among species of spiders and also their evolutionary origin by means of phylogenetic analyses. We also conducted tests to assess the action of natural selection in their evolution combined to structural modelling of the affected sites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The majority of the Class I enzymes belong to the same clade, which indicates a recent evolution from a single common ancestor. Positively selected sites are located on the catalytic interface, which contributes to a distinct surface charge distribution between the classes. Sites that may prevent the formation of an additional bridge were found in Class I enzymes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The evolution of Sphingomyelinase D has been driven by natural selection toward an increase in noxiousness, and this might help explain the toxic variation between classes.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12862-015-0561-4","type":"journal-article","created":{"date-parts":[[2015,12,21]],"date-time":"2015-12-21T11:41:18Z","timestamp":1450698078000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Adaptive evolution in the toxicity of a spider\u2019s venom enzymes"],"prefix":"10.1186","volume":"15","author":[{"given":"Aur\u00e9lio","family":"Pedroso","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio Russo","family":"Matioli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario Tyago","family":"Murakami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giselle","family":"Pidde-Queiroz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise V.","family":"Tambourgi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2015,12,21]]},"reference":[{"key":"561_CR1","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/0003-9861(78)90046-2","volume":"187","author":"LJ Forrester","year":"1978","unstructured":"Forrester LJ, Barrett JT, Campbell BJ. 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