title: The Deep Origin and Recent Loss of Venom Toxin Genes in Rattlesnakes.
abstract: The genetic origin of novel traits is a central but challenging puzzle in evolutionary biology. Among snakes, phospholipase A2 (PLA2)-related toxins have evolved in different lineages to function as potent neurotoxins, myotoxins, or hemotoxins. Here, we traced the genomic origin and evolution of PLA2 toxins by examining PLA2 gene number, organization, and expression in both neurotoxic and non-neurotoxic rattlesnakes. We found that even though most North American rattlesnakes do not produce neurotoxins, the genes of a specialized heterodimeric neurotoxin predate the origin of rattlesnakes and were present in their last common ancestor (∼22 mya). The neurotoxin genes were then deleted independently in the lineages leading to the Western Diamondback (Crotalus atrox) and Eastern Diamondback (C. adamanteus) rattlesnakes (∼6 mya), while a PLA2 myotoxin gene retained in C. atrox was deleted from the neurotoxic Mojave rattlesnake (C. scutulatus; ∼4 mya). The rapid evolution of PLA2 gene number appears to be due to transposon invasion that provided a template for non-allelic homologous recombination.
authors.affiliation: Howard Hughes Medical Institute and Laboratory of Molecular Biology, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI 53706, USA. Electronic address: ndowell@wisc.edu.
authors.forename: Noah L
authors.initials: NL
authors.lastname: Dowell
authors.affiliation: Howard Hughes Medical Institute and Laboratory of Molecular Biology, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI 53706, USA.
authors.forename: Matt W
authors.initials: MW
authors.lastname: Giorgianni
authors.affiliation: Howard Hughes Medical Institute and Laboratory of Molecular Biology, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI 53706, USA.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Kassner
authors.affiliation: Howard Hughes Medical Institute and Laboratory of Molecular Biology, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI 53706, USA.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Selegue
authors.affiliation: National Natural Toxins Research Center and Department of Chemistry, Texas A&M University-Kingsville, MSC 224, Kingsville, TX 78363, USA.
authors.forename: Elda E
authors.initials: EE
authors.lastname: Sanchez
authors.affiliation: Howard Hughes Medical Institute and Laboratory of Molecular Biology, University of Wisconsin-Madison, 1525 Linden Drive, Madison, WI 53706, USA. Electronic address: sbcarrol@wisc.edu.
authors.forename: Sean B
authors.initials: SB
authors.lastname: Carroll
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003435:Crotalid Venoms / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017839:Crotalus / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D054467:Phospholipases A2 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D010802:Phylogeny; D030162:Reptilian Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D013045:Species Specificity
chemical_list: D003435:Crotalid Venoms; D030162:Reptilian Proteins; D054467:Phospholipases A2
keywords: gene duplication; gene expression; gene loss; genome sequencing; neurotoxin; novelty; phospholipase A2; rattlesnake; transposable elements; venom