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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.


Predators and prey driving accelerated evolution of scorpion α-toxins.Birds, lizards and mammals are selected as representatives of scorpion’s predators and insects as a representative of scorpion’s prey. The toxins shown here all stem from M. martensii with the core-domain-derived PSSs in different colors, including cyan (BmKM1); red (BmKM4); brown (BmKM7); tint (BmKM8); blue, BmKαTX10; green, BmKαTX17; pink, BmKmX4; and yellow, BmKSCT (Fig. S1). Evolutionarily variable and conserved loops are colored cyan and brown, respectively, in the channel schematic diagram. The image of the bird was photographed by Prof. Sun Yuehua and others by the authors.
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f8: Predators and prey driving accelerated evolution of scorpion α-toxins.Birds, lizards and mammals are selected as representatives of scorpion’s predators and insects as a representative of scorpion’s prey. The toxins shown here all stem from M. martensii with the core-domain-derived PSSs in different colors, including cyan (BmKM1); red (BmKM4); brown (BmKM7); tint (BmKM8); blue, BmKαTX10; green, BmKαTX17; pink, BmKmX4; and yellow, BmKSCT (Fig. S1). Evolutionarily variable and conserved loops are colored cyan and brown, respectively, in the channel schematic diagram. The image of the bird was photographed by Prof. Sun Yuehua and others by the authors.

Mentions: In the toxin-channel complex, we have established several pairs of interactions, in which three channel sites located in the two loops are involved in interaction with the PSSs of toxins, including 1560, 1611 and 1613 (Fig. 3), and two of them exhibit a side-chain variability: 1560: E/K/Q/T/V in birds, D/E/I/K/T/V in lizards, E/D/K/S/T/V in mammals, N/S/T in insects; 1613: E/D/G/K in birds, E/D/G/K/Q in lizards, A/D/E/G/T in mammals. Besides these point mutations, LDIVS3-S4 also contains some insertion/deletion (indel) mutations in birds and mammals (Figs. S2–S4). Collectively, these variable toxin-bound sites derived from the predators and prey may drive accelerated changes of their interacting residues (PSSs) in scorpion toxins for maintaining abilities in both defense and attack during evolution (Fig. 8). These observations also account for evolutionary rationality of gene duplication of scorpion toxins in a specific species since multiple toxin members may facilitate to deal with a diversity of competitor species via rapidly changing their bioactive surfaces by positive selection (Fig. 8). Given that the majority of animal toxins exist in a multigene form41, our finding may be of general significance in understanding forces driving the evolution of these toxins in diverse venomous species.


Target-Driven Evolution of Scorpion Toxins.

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

Predators and prey driving accelerated evolution of scorpion α-toxins.Birds, lizards and mammals are selected as representatives of scorpion’s predators and insects as a representative of scorpion’s prey. The toxins shown here all stem from M. martensii with the core-domain-derived PSSs in different colors, including cyan (BmKM1); red (BmKM4); brown (BmKM7); tint (BmKM8); blue, BmKαTX10; green, BmKαTX17; pink, BmKmX4; and yellow, BmKSCT (Fig. S1). Evolutionarily variable and conserved loops are colored cyan and brown, respectively, in the channel schematic diagram. The image of the bird was photographed by Prof. Sun Yuehua and others by the authors.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f8: Predators and prey driving accelerated evolution of scorpion α-toxins.Birds, lizards and mammals are selected as representatives of scorpion’s predators and insects as a representative of scorpion’s prey. The toxins shown here all stem from M. martensii with the core-domain-derived PSSs in different colors, including cyan (BmKM1); red (BmKM4); brown (BmKM7); tint (BmKM8); blue, BmKαTX10; green, BmKαTX17; pink, BmKmX4; and yellow, BmKSCT (Fig. S1). Evolutionarily variable and conserved loops are colored cyan and brown, respectively, in the channel schematic diagram. The image of the bird was photographed by Prof. Sun Yuehua and others by the authors.
Mentions: In the toxin-channel complex, we have established several pairs of interactions, in which three channel sites located in the two loops are involved in interaction with the PSSs of toxins, including 1560, 1611 and 1613 (Fig. 3), and two of them exhibit a side-chain variability: 1560: E/K/Q/T/V in birds, D/E/I/K/T/V in lizards, E/D/K/S/T/V in mammals, N/S/T in insects; 1613: E/D/G/K in birds, E/D/G/K/Q in lizards, A/D/E/G/T in mammals. Besides these point mutations, LDIVS3-S4 also contains some insertion/deletion (indel) mutations in birds and mammals (Figs. S2–S4). Collectively, these variable toxin-bound sites derived from the predators and prey may drive accelerated changes of their interacting residues (PSSs) in scorpion toxins for maintaining abilities in both defense and attack during evolution (Fig. 8). These observations also account for evolutionary rationality of gene duplication of scorpion toxins in a specific species since multiple toxin members may facilitate to deal with a diversity of competitor species via rapidly changing their bioactive surfaces by positive selection (Fig. 8). Given that the majority of animal toxins exist in a multigene form41, our finding may be of general significance in understanding forces driving the evolution of these toxins in diverse venomous species.

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.