title: Venomics of New World pit vipers: genus-wide comparisons of venom proteomes across Agkistrodon.
abstract: We report a genus-wide comparison of venom proteome variation across New World pit vipers in the genus Agkistrodon. Despite the wide variety of habitats occupied by this genus and that all its taxa feed on diverse species of vertebrates and invertebrate prey, the venom proteomes of copperheads, cottonmouths, and cantils are remarkably similar, both in the type and relative abundance of their different toxin families. The venoms from all the eleven species and subspecies sampled showed relatively similar proteolytic and PLA2 activities. In contrast, quantitative differences were observed in hemorrhagic and myotoxic activities in mice. The highest myotoxic activity was observed with the venoms of A. b. bilineatus, followed by A. p. piscivorus, whereas the venoms of A. c. contortrix and A. p. leucostoma induced the lowest myotoxic activity. The venoms of Agkistrodon bilineatus subspecies showed the highest hemorrhagic activity and A. c. contortrix the lowest. Compositional and toxicological analyses agree with clinical observations of envenomations by Agkistrodon in the USA and Central America. A comparative analysis of Agkistrodon shows that venom divergence tracks phylogeny of this genus to a greater extent than in Sistrurus rattlesnakes, suggesting that the distinct natural histories of Agkistrodon and Sistrurus clades may have played a key role in molding the patterns of evolution of their venom protein genes.
  
  
  CONCLUSIONS
  A deep understanding of the structural and functional profiles of venoms and of the principles governing the evolution of venomous systems is a goal of venomics. Isolated proteomics analyses have been conducted on venoms from many species of vipers and pit vipers. However, making sense of these large inventories of data requires the integration of this information across multiple species to identify evolutionary and ecological trends. Our genus-wide venomics study provides a comprehensive overview of the toxic arsenal across Agkistrodon and a ground for understanding the natural histories of, and clinical observations of envenomations by, species of this genus.
authors.affiliation: Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica. Electronic address: bruno.lomonte@ucr.ac.cr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Lomonte
authors.affiliation: Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Wan-Chih
authors.initials: WC
authors.lastname: Tsai
authors.affiliation: Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Ureña-Diaz
authors.affiliation: Laboratorio de Venómica y Proteinómica Estructural, Instituto de Biomedicina de Valencia, CSIC, Valencia, Spain.
authors.forename: Libia
authors.initials: L
authors.lastname: Sanz
authors.affiliation: Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
authors.forename: Diana
authors.initials: D
authors.lastname: Mora-Obando
authors.affiliation: National Natural Toxins Research Center, Department of Chemistry, Texas A&M University-Kingsville, MSC 224, 975 West Avenue B, Kingsville, TX 78363, USA.
authors.forename: Elda E
authors.initials: EE
authors.lastname: Sánchez
authors.affiliation: Venom Evolution Lab, School of Biological Sciences, University of Queensland, St. Lucia, Qld 4072, Australia.
authors.forename: Bryan G
authors.initials: BG
authors.lastname: Fry
authors.affiliation: Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
authors.forename: José María
authors.initials: JM
authors.lastname: Gutiérrez
authors.affiliation: Department of Evolution, Ecology, and Organismal Biology, Ohio State University, Columbus, OH 43210, USA.
authors.forename: H Lisle
authors.initials: HL
authors.lastname: Gibbs
authors.affiliation: Department of Evolution, Ecology, and Organismal Biology, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Sovic
authors.affiliation: Laboratorio de Venómica y Proteinómica Estructural, Instituto de Biomedicina de Valencia, CSIC, Valencia, Spain. Electronic address: jcalvete@ibv.csic.es.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Calvete
mesh_terms: D017836:Agkistrodon / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003435:Crotalid Venoms / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D003435:Crotalid Venoms; D020543:Proteome
keywords: Genus Agkistrodon; Mass spectrometry; Snake venomics