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Target-Driven Evolution of Scorpion Toxins.

Zhang S, Gao B, Zhu S - Sci Rep (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Different divergence rates between scorpion toxin-bound regions and non-bound regions of Nav channels.Three fixed-sites models (D–F) were used to calculate ω values for two partitions of the VSD in Nav channels from birds, lizards, mammals and insects: one partition representing the scorpion toxin-bound regions (two extracellular loops, bars in light green) and the other the four transmembrane helices and the intracellular loop (bars in orange).
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f5: Different divergence rates between scorpion toxin-bound regions and non-bound regions of Nav channels.Three fixed-sites models (D–F) were used to calculate ω values for two partitions of the VSD in Nav channels from birds, lizards, mammals and insects: one partition representing the scorpion toxin-bound regions (two extracellular loops, bars in light green) and the other the four transmembrane helices and the intracellular loop (bars in orange).

Mentions: To provide further evidence for relaxed purifying selection in the toxin-bound regions (LDIVS1-S2 and LDIVS3-S4) of Nav channels, we employed six fixed-sites models (A to F, from simple to complex) developed by Yang and Swanson36 to compare their ω values with those of the non-toxin-bound regions (S1–S4 and the intracellular loop) from the four different lineages. As shown in Supplementary Tables 2 to 5, in all the lineages, the three more complex models (D, E, and F) that assume different ω ratios between two partitions convergently fit the data better than the three more simple models (A, B, and C). For example, the LRT statistics between C and E are 14.4 for birds, 33.0 for lizards, 43.2 for mammals, and 12.4 for insects (p < 0.005) (Table S2–Table S5). These models all suggest that the two partitions have very different ω values and overall the toxin-bound regions evolved two folds more quickly than its neighboring regions (Fig. 5), in line with the opinion of relaxation of purifying selection in these extracellular loops (Fig. 4).


Target-Driven Evolution of Scorpion Toxins.

Zhang S, Gao B, Zhu S - Sci Rep (2015)

Different divergence rates between scorpion toxin-bound regions and non-bound regions of Nav channels.Three fixed-sites models (D–F) were used to calculate ω values for two partitions of the VSD in Nav channels from birds, lizards, mammals and insects: one partition representing the scorpion toxin-bound regions (two extracellular loops, bars in light green) and the other the four transmembrane helices and the intracellular loop (bars in orange).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4595728&req=5

f5: Different divergence rates between scorpion toxin-bound regions and non-bound regions of Nav channels.Three fixed-sites models (D–F) were used to calculate ω values for two partitions of the VSD in Nav channels from birds, lizards, mammals and insects: one partition representing the scorpion toxin-bound regions (two extracellular loops, bars in light green) and the other the four transmembrane helices and the intracellular loop (bars in orange).
Mentions: To provide further evidence for relaxed purifying selection in the toxin-bound regions (LDIVS1-S2 and LDIVS3-S4) of Nav channels, we employed six fixed-sites models (A to F, from simple to complex) developed by Yang and Swanson36 to compare their ω values with those of the non-toxin-bound regions (S1–S4 and the intracellular loop) from the four different lineages. As shown in Supplementary Tables 2 to 5, in all the lineages, the three more complex models (D, E, and F) that assume different ω ratios between two partitions convergently fit the data better than the three more simple models (A, B, and C). For example, the LRT statistics between C and E are 14.4 for birds, 33.0 for lizards, 43.2 for mammals, and 12.4 for insects (p < 0.005) (Table S2–Table S5). These models all suggest that the two partitions have very different ω values and overall the toxin-bound regions evolved two folds more quickly than its neighboring regions (Fig. 5), in line with the opinion of relaxation of purifying selection in these extracellular loops (Fig. 4).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.