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Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/282293
Dataset. 2015

DATA FROM: MEDICALLY IMPORTANT DIFFERENCES IN SNAKE VENOM COMPOSITION ARE DICTATED BY DISTINCT POSTGENOMIC MECHANISMS

  • Casewell, Nicholas R.
  • Wagstaff, Simon C.
  • Wüster, Wolfgang
  • Cook, Darren A. N.
  • Bolton, Fiona M. S.
  • King, Sarah I.
  • Pla, Davinia
  • Sanz, Libia
  • Calvete, Juan J.
  • Harrison, Robert A.
crisp_dna DNA alignment of the cysteine rich secretory protein (CRISP) toxin family LAAO_dna DNA alignment of the L-amino acid oxidase (LAAO) toxin family lectin_dna DNA alignment of the C-type lectin (CTL) toxin family pla2_dna DNA alignment of the phospholipase A2 (PLA2) toxin family serine_protease_dna DNA alignment of the serine protease (SP) toxin family svmp_dna DNA alignment of the snake venom metalloproteinase (SVMP) toxin family, Variation in venom composition is a ubiquitous phenomenon in snakes and occurs both interspecifically and intraspecifically. Venom variation can have severe outcomes for snakebite victims by rendering the specific antibodies found in antivenoms ineffective against heterologous toxins found in different venoms. The rapid evolutionary expansion of different toxin-encoding gene families in different snake lineages is widely perceived as the main cause of venom variation. However, this view is simplistic and disregards the understudied influence that processes acting on gene transcription and translation may have on the production of the venom proteome. Here, we assess the venom composition of six related viperid snakes and compare interspecific changes in the number of toxin genes, their transcription in the venom gland, and their translation into proteins secreted in venom. Our results reveal that multiple levels of regulation are responsible for generating variation in venom composition between related snake species. We demonstrate that differential levels of toxin transcription, translation, and their posttranslational modification have a substantial impact upon the resulting venom protein mixture. Notably, these processes act to varying extents on different toxin paralogs found in different snakes and are therefore likely to be as important as ancestral gene duplication events for generating compositionally distinct venom proteomes. Our results suggest that these processes may also contribute to altering the toxicity of snake venoms, and we demonstrate how this variability can undermine the treatment of a neglected tropical disease, snakebite., Peer reviewed

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