Venomous cone snails: molecular phylogeny and the generation of toxin diversity.

In order to investigate the generation of conotoxin diversity, delta-conotoxin sequences from nine Conus species were analyzed in the context of their phylogeny. Using a standard molecular marker, mitochondrial 16S RNA, we determined that the delta-conotoxins were derived from three distinct species clades based on the phylogenetic reconstruction of a large set (>80) of Conus species and other toxoglossate molluscs. Four different mechanisms appear to have contributed to the diversity of the delta-conotoxins analyzed: (1) Speciation: Delta-conotoxins in different species diverge from each other (the prepro regions of orthologous genes somewhat more slowly than the reference rRNA rate, the mature toxin regions significantly faster). (2) Duplication: Intraspecific delta-conotoxin divergence is initiated by gene duplication events, some of which may have predated the species itself. (3) Recombination: A novel delta-conotoxin may arise through recombination of two parental delta-contoxin genes. (4) 'Focal hypermutation': This sudden, almost saltatory change in sequence is always restricted to the mature toxin region. The first three have been recognized previously as mechanisms important for the evolution of gene families in other phylogenetic systems; the last is a remarkable, mechanistically unexplained and specialized feature of Conus peptide diversification.

[1]  M. Spira,et al.  Alteration of Sodium Currents by New Peptide Toxins From the Venom of a Molluscivorous Conus Snail , 1993, The European journal of neuroscience.

[2]  S. Woodward,et al.  A molluscivorous Conus toxin: conserved frameworks in conotoxins. , 1989, Biochemistry.

[3]  B. Olivera,et al.  Speciation of Cone Snails and Interspecific Hyperdivergence of Their Venom Peptides: Potential Evolutionary Significance of Introns a , 1999, Annals of the New York Academy of Sciences.

[4]  Walter Stühmer,et al.  Strategy for rapid immobilization of prey by a fish-hunting marine snail , 1996, Nature.

[5]  M. Spira,et al.  Mollusc-specific toxins from the venom of Conus textile neovicarius. , 1991, European journal of biochemistry.

[6]  B. Olivera,et al.  E.E. Just Lecture, 1996. Conus venom peptides, receptor and ion channel targets, and drug design: 50 million years of neuropharmacology. , 1997, Molecular biology of the cell.

[7]  Y. Gilad,et al.  Mechanisms for evolving hypervariability: the case of conopeptides. , 2001, Molecular biology and evolution.

[8]  J. Imperial,et al.  Precursor structure of ω-conotoxin GVIA determined from a cDNA clone , 1992 .

[9]  S. Woodward,et al.  Constant and hypervariable regions in conotoxin propeptides. , 1990, The EMBO journal.

[10]  W. Stühmer,et al.  κ-Conotoxin Pviia Is a Peptide Inhibiting theShaker K+ Channel* , 1998, The Journal of Biological Chemistry.

[11]  S. Palumbi,et al.  Molecular genetics of ecological diversification: duplication and rapid evolution of toxin genes of the venomous gastropod Conus. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[12]  S. Woodward,et al.  Diversity of Conus neuropeptides. , 1990, Science.

[13]  S. Palumbi,et al.  Developmental shifts and species selection in gastropods. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[14]  W R Gray,et al.  Delta-conotoxin GmVIA, a novel peptide from the venom of Conus gloriamaris. , 1994, Biochemistry.

[15]  C. J. Poklemba,et al.  A rapid one-tube genomic DNA extraction process for PCR and RAPD analyses , 1995, Nucleic Acids Res..

[16]  M. Adams,et al.  CALCIUM CHANNEL DIVERSITY AND NEUROTRANSMITTER RELEASE : THE OMEGA -CONOTOXINS AND OMEGA -AGATOXINS , 1994 .

[17]  G. Glusman,et al.  Position-specific codon conservation in hypervariable gene families. , 2000, Trends in genetics : TIG.

[18]  W R Gray,et al.  Purification, characterization, synthesis, and cloning of the lockjaw peptide from Conus purpurascens venom. , 1995, Biochemistry.