title: Target-Driven Evolution of Scorpion Toxins.
abstract: It is long known that peptide neurotoxins derived from a diversity of venomous animals evolve by positive selection following gene duplication, yet a force that drives their adaptive evolution remains a mystery. By using maximum-likelihood models of codon substitution, we analyzed molecular adaptation in scorpion sodium channel toxins from a specific species and found ten positively selected sites, six of which are located at the core-domain of scorpion α-toxins, a region known to interact with two adjacent loops in the voltage-sensor domain (DIV) of sodium channels, as validated by our newly constructed computational model of toxin-channel complex. Despite the lack of positive selection signals in these two loops, they accumulated extensive sequence variations by relaxed purifying selection in prey and predators of scorpions. The evolutionary variability in the toxin-bound regions of sodium channels indicates that accelerated substitutions in the multigene family of scorpion toxins is a consequence of dealing with the target diversity. This work presents an example of atypical co-evolution between animal toxins and their molecular targets, in which toxins suffered from more prominent selective pressure from the channels of their competitors. Our discovery helps explain the evolutionary rationality of gene duplication of toxins in a specific venomous species.
authors.affiliation: Group of Peptide Biology and Evolution, State Key Laboratory of Integrated Management of Pest Insects &Rodents, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, 100101 Beijing, China.
authors.forename: Shangfei
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Group of Peptide Biology and Evolution, State Key Laboratory of Integrated Management of Pest Insects &Rodents, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, 100101 Beijing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Gao
authors.affiliation: Group of Peptide Biology and Evolution, State Key Laboratory of Integrated Management of Pest Insects &Rodents, Institute of Zoology, Chinese Academy of Sciences, 1 Beichen West Road, Chaoyang District, 100101 Beijing, China.
authors.forename: Shunyi
authors.initials: S
authors.lastname: Zhu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001717:Birds / Q000502:physiology; D019143:Evolution, Molecular; D020387:Food Chain; D020440:Gene Duplication; D015870:Gene Expression; D014644:Genetic Variation; D007313:Insecta / Q000502:physiology; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D005810:Multigene Family; D009498:Neurotoxins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012104:Reptiles / Q000502:physiology; D012604:Scorpion Venoms / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012605:Scorpions / Q000472:pathogenicity / Q000502:physiology*; D061566:Voltage-Gated Sodium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D009498:Neurotoxins; D012604:Scorpion Venoms; D061566:Voltage-Gated Sodium Channels