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dc.creatorDurban, Jordi
dc.creatorPérez, Alicia
dc.creatorSanz, Libia
dc.creatorGómez Argüello, Aarón
dc.creatorBonilla Murillo, Fabián
dc.creatorRodríguez Arguedas, Santos
dc.creatorChacón Gutiérrez, Danilo
dc.creatorSasa Marín, Mahmood
dc.creatorAngulo Ugalde, Yamileth
dc.creatorGutiérrez, José María
dc.creatorCalvete Chornet, Juan José
dc.description.abstractBackground Understanding the processes that drive the evolution of snake venom is a topic of great research interest in molecular and evolutionary toxinology. Recent studies suggest that ontogenetic changes in venom composition are genetically controlled rather than environmentally induced. However, the molecular mechanisms underlying these changes remain elusive. Here we have explored the basis and level of regulation of the ontogenetic shift in the venom composition of the Central American rattlesnake, Crotalus s. simus using a combined proteomics and transcriptomics approach. Results Proteomic analysis showed that the ontogenetic shift in the venom composition of C. s. simus is essentially characterized by a gradual reduction in the expression of serine proteinases and PLA2 molecules, particularly crotoxin, a β-neurotoxic heterodimeric PLA2, concominantly with an increment of PI and PIII metalloproteinases at age 9–18 months. Comparison of the transcriptional activity of the venom glands of neonate and adult C. s. simus specimens indicated that their transcriptomes exhibit indistinguisable toxin family profiles, suggesting that the elusive mechanism by which shared transcriptomes generate divergent venom phenotypes may operate post-transcriptionally. Specifically, miRNAs with frequency count of 1000 or greater exhibited an uneven distribution between the newborn and adult datasets. Of note, 590 copies of a miRNA targeting crotoxin B-subunit was exclusively found in the transcriptome of the adult snake, whereas 1185 copies of a miRNA complementary to a PIII-SVMP mRNA was uniquely present in the newborn dataset. These results support the view that age-dependent changes in the concentration of miRNA modulating the transition from a crotoxin-rich to a SVMP-rich venom from birth through adulhood can potentially explain what is observed in the proteomic analysis of the ontogenetic changes in the venom composition of C. s. simus. Conclusions Existing snake venom toxins are the result of early recruitment events in the Toxicofera clade of reptiles by which ordinary genes were duplicated, and the new genes selectively expressed in the venom gland and amplified to multigene families with extensive neofunctionalization throughout the approximately 112–125 million years of ophidian evolution. Our findings support the view that understanding the phenotypic diversity of snake venoms requires a deep knowledge of the mechanisms regulating the transcriptional and translational activity of the venom gland. Our results suggest a functional role for miRNAs. The impact of specific miRNAs in the modulation of venom composition, and the integration of the mechanisms responsible for the generation of these miRNAs in the evolutionary landscape of the snake's venom gland, are further challenges for future research.es_ES
dc.description.sponsorshipMinisterio de Economía y Competitividad/[BFU2010-17373]//Españaes_ES
dc.description.sponsorshipGeneralitat Valenciana/[PROMETEO/2010/005]//Españaes_ES
dc.description.sponsorshipUniversidad de Costa Rica/[741-B2-093]/UCR/Costa Ricaes_ES
dc.description.sponsorshipPrograma Iberoamericano de Ciencia y Tecnología para el Desarrollo/206AC0281/CYTED/Españaes_ES
dc.rightsAtribución-NoComercial-CompartirIgual 3.0 Costa Rica*
dc.sourceBMC Genomics; Volumen 14, Número 234. 2013es_ES
dc.subjectOntogenetic venom shiftes_ES
dc.subjectSnake venom gland transcriptomicses_ES
dc.subject454 pyrosequencinges_ES
dc.subjectIon-Torrent microRNA profilinges_ES
dc.subjectCrotalus simus simuses_ES
dc.subjectSnake venomes_ES
dc.titleIntegrated “omics” profiling indicates that miRNAs are modulators of the ontogenetic venom composition shift in the Central American rattlesnake, Crotalus simus simuses_ES
dc.typeartículo original
dc.description.procedenceUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP)es_ES

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Atribución-NoComercial-CompartirIgual 3.0 Costa Rica
Except where otherwise noted, this item's license is described as Atribución-NoComercial-CompartirIgual 3.0 Costa Rica