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Molecular Evolution, Functional Variation, and Proposed Nomenclature of the Gene Family That Includes Sphingomyelinase D in Sicariid Spider Venoms

Binford, Greta J ; Bodner, Melissa R ; Cordes, Matthew H.J ; Baldwin, Katherine L ; Rynerson, Melody R ; Burns, Scott N ; Zobel-Thropp, Pamela A

Molecular biology and evolution, 2009-03, Vol.26 (3), p.547-566 [Periódico revisado por pares]

United States: Oxford University Press

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  • Título:
    Molecular Evolution, Functional Variation, and Proposed Nomenclature of the Gene Family That Includes Sphingomyelinase D in Sicariid Spider Venoms
  • Autor: Binford, Greta J ; Bodner, Melissa R ; Cordes, Matthew H.J ; Baldwin, Katherine L ; Rynerson, Melody R ; Burns, Scott N ; Zobel-Thropp, Pamela A
  • Assuntos: Animals ; Araneae ; Enzymes ; Evolution, Molecular ; Evolutionary biology ; Gene Duplication ; Loxosceles ; Loxosceles rufescens ; Molecular biology ; Multigene Family ; Phosphoric Diester Hydrolases - genetics ; Phylogeny ; Selection, Genetic ; Spider Venoms - enzymology ; Spiders ; Toxicology
  • É parte de: Molecular biology and evolution, 2009-03, Vol.26 (3), p.547-566
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
    Adriana Briscoe, Associate Editor
    Present address: Department of Cellular and Molecular Biology, University of Wisconsin, Madison, WI.
    Present address: Department of Zoology, University of British Columbia, Vancouver, BC, Canada.
    Present address: Department of Genome Sciences, University of Washington, Seattle, WA.
  • Descrição: The venom enzyme sphingomyelinase D (SMase D) in the spider family Sicariidae (brown or fiddleback spiders [Loxosceles] and six-eyed sand spiders [Sicarius]) causes dermonecrosis in mammals. SMase D is in a gene family with multiple venom-expressed members that vary in functional specificity. We analyze molecular evolution of this family and variation in SMase D activity among crude venoms using a data set that represents the phylogenetic breadth of Loxosceles and Sicarius. We isolated a total of 190 nonredundant nucleotide sequences encoding 168 nonredundant amino acid sequences of SMase D homologs from 21 species. Bayesian phylogenies support two major clades that we name α and β, within which we define seven and three subclades, respectively. Sequences in the α clade are exclusively from New World Loxosceles and Loxosceles rufescens and include published genes for which expression products have SMase D and dermonecrotic activity. The β clade includes paralogs from New World Loxosceles that have no, or reduced, SMase D and no dermonecrotic activity and also paralogs from Sicarius and African Loxosceles of unknown activity. Gene duplications are frequent, consistent with a birth-and-death model, and there is evidence of purifying selection with episodic positive directional selection. Despite having venom-expressed SMase D homologs, venoms from New World Sicarius have reduced, or no, detectable SMase D activity, and Loxosceles in the Southern African spinulosa group have low SMase D activity. Sequence conservation mapping shows >98% conservation of proposed catalytic residues of the active site and around a plug motif at the opposite end of the TIM barrel, but α and β clades differ in conservation of key residues surrounding the apparent substrate binding pocket. Based on these combined results, we propose an inclusive nomenclature for the gene family, renaming it SicTox, and discuss emerging patterns of functional diversification.
  • Editor: United States: Oxford University Press
  • Idioma: Inglês
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