Integrated “omics” profiling indicates that miRNAs are modulators of the ontogenetic venom composition shift in the Central American rattlesnake, Crotalus simus simus
Gómez Argüello, Aarón
Bonilla Murillo, Fabián
Rodríguez Arguedas, Santos
Chacón Gutiérrez, Danilo
Angulo Ugalde, Yamileth
Gutiérrez, José María
Calvete, Juan J.
MetadatosMostrar el registro completo del ítem
Background 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.
Enlace externo al ítem10.1186/1471-2164-14-234
- Microbiología 
El ítem tiene asociados los siguientes ficheros de licencia:
Excepto si se señala otra cosa, la licencia del ítem se describe como Atribución-NoComercial-CompartirIgual 3.0 Costa Rica
Mostrando ítems relacionados por Título, autor o materia.
Impact of Regional Variation in Bothrops asper Snake Venom on the Design of Antivenoms: Integrating Antivenomics and Neutralization Approaches Gutiérrez, José María; Sanz, Libia; Flores Díaz, Marietta; Figueroa, Lucía; Madrigal Villalobos, Marvin; Herrera Vega, María; Villalta, Mauren; León Montero, Guillermo; Estrada Umaña, Ricardo; Borges, Adolfo; Alape Girón, Alberto; Calvete, Juan J. (2010-10-21)Intraspecific snake venom variations have implications in the preparation of venom pools for the generation of antivenoms. The impact of such variation in the cross-reactivity of antivenoms against Bothrops asper venom was ...
Comparative study of the cytolytic activity of myotoxic phospholipases A2 on mouse endothelial (tEnd) and skeletal muscle (C2C12) cells in vitro Lomonte, Bruno; Angulo Ugalde, Yamileth; Rufini, Stefano; Cho, Wonhwa; Giglio, José Roberto; Ohno, Motoroni; Daniele, José Julían; Geoghegan, Patricia; Gutiérrez, José María (1999-01)A rapid in vitro cytolytic effect of some myotoxic phospholipases A2 (PLA2s) isolated from the venoms of Viperidae snakes has been previously described. This study was undertaken to investigate if cytolytic activity is a ...
Snake venomics and antivenomics: Proteomic tools in the design and control of antivenoms for the treatment of snakebite envenoming Gutiérrez, José María; Lomonte, Bruno; León Montero, Guillermo; Alape Girón, Alberto; Flores Díaz, Marietta; Sanz, Libia; Angulo Ugalde, Yamileth; Calvete, Juan J. (2009-03-06)Snakebite envenoming represents a neglected tropical disease that has a heavy public health impact, particularly in Asia, Africa and Latin America. A global initiative, aimed at increasing antivenom production and ...