title: Trends in the Evolution of Snake Toxins Underscored by an Integrative Omics Approach to Profile the Venom of the Colubrid Phalotris mertensi.
abstract: Only few studies on snake venoms were dedicated to deeply characterize the toxin secretion of animals from the Colubridae family, despite the fact that they represent the majority of snake diversity. As a consequence, some evolutionary trends observed in venom proteins that underpinned the evolutionary histories of snake toxins were based on data from a minor parcel of the clade. Here, we investigated the proteins of the totally unknown venom from Phalotris mertensi (Dipsadinae subfamily), in order to obtain a detailed profile of its toxins and to appreciate evolutionary tendencies occurring in colubrid venoms. By means of integrated omics and functional approaches, including RNAseq, Sanger sequencing, high-resolution proteomics, recombinant protein production, and enzymatic tests, we verified an active toxic secretion containing up to 21 types of proteins. A high content of Kunitz-type proteins and C-type lectins were observed, although several enzymatic components such as metalloproteinases and an L-amino acid oxidase were also present in the venom. Interestingly, an arguable venom component of other species was demonstrated as a true venom protein and named svLIPA (snake venom acid lipase). This finding indicates the importance of checking the actual protein occurrence across species before rejecting genes suggested to code for toxins, which are relevant for the discussion about the early evolution of reptile venoms. Moreover, trends in the evolution of some toxin classes, such as simplification of metalloproteinases and rearrangements of Kunitz and Wap domains, parallel similar phenomena observed in other venomous snake families and provide a broader picture of toxin evolution.
authors.affiliation: Laboratório Especial de Toxinologia Aplicada, Center of Toxins, Immune-Response and Cell Signaling (CeTICS), Instituto Butantan, São Paulo, Brazil.
authors.forename: Pollyanna Fernandes
authors.initials: PF
authors.lastname: Campos
authors.affiliation: Laboratório Especial de Toxinologia Aplicada, Center of Toxins, Immune-Response and Cell Signaling (CeTICS), Instituto Butantan, São Paulo, Brazil.
authors.forename: Débora
authors.initials: D
authors.lastname: Andrade-Silva
authors.affiliation: Departamento de Ciência E Tecnologia, Universidade Federal de São Paulo, São José Dos Campos, Brazil.
authors.forename: André
authors.initials: A
authors.lastname: Zelanis
authors.affiliation: Laboratório Nacional de Biociências (LNBio), Campinas, Brazil.
authors.forename: Adriana Franco
authors.initials: AF
authors.lastname: Paes Leme
authors.affiliation: Laboratório de Herpetologia, Instituto Butantan, São Paulo, Brazil.
authors.forename: Marisa Maria Teixeira
authors.initials: MM
authors.lastname: Rocha
authors.affiliation: Laboratório Especial de Toxinologia Aplicada, Center of Toxins, Immune-Response and Cell Signaling (CeTICS), Instituto Butantan, São Paulo, Brazil.
authors.forename: Milene Cristina
authors.initials: MC
authors.lastname: Menezes
authors.affiliation: Laboratório Especial de Toxinologia Aplicada, Center of Toxins, Immune-Response and Cell Signaling (CeTICS), Instituto Butantan, São Paulo, Brazil.
authors.forename: Solange M T
authors.initials: SM
authors.lastname: Serrano
authors.affiliation: Laboratório Especial de Toxinologia Aplicada, Center of Toxins, Immune-Response and Cell Signaling (CeTICS), Instituto Butantan, São Paulo, Brazil inacio.azevedo@butantan.gov.br.
authors.forename: Inácio de Loiola Meirelles
authors.initials: Ide L
authors.lastname: Junqueira-de-Azevedo
mesh_terms: D000818:Animals; D017812:Colubridae / Q000235:genetics*; D019143:Evolution, Molecular; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D012910:Snake Venoms / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome
chemical_list: D037181:Lectins, C-Type; D020543:Proteome; D012910:Snake Venoms; D008049:Lipase
keywords: acid lipase; molecular evolution; proteome; snake; transcriptome; venom