Molecular evolution of scorpion α-toxins——Accelerated substitutions and functional divergence  

作　　者：ZHU Shunyi and LI Wenxin(Department of Biotechnology, College of Life Sciences, Wuhan University, Wuhan 430072, China) 

出　　处：《Progress in Natural Science:Materials International》2002年第2期30-36,84,共8页自然科学进展·国际材料（英文版）

基　　金：Supported by the National Natural Science Foundation of China (Grant No. 39970897)

摘　　要：Scorpion a-toxins are a family of toxic proteins with similar scaffold, but possess divergent pharmacological properties. Analysis of cDNA sequences reveals that the numbers of nucleotide substitutions per site (K) for 5’ and 3’ UTRs are smaller than those per synonymous site (Ks) for the mature peptide-coding sequences, whereas the numbers of nucleotide substitutions per nonsynonymous site (Ka) are close to or larger than Ks values for relevant pairs of cDNAs. These results, together with phylogenetic analysis, indicate that scorpion α-toxins have evolved by accelerated substitutions in the mature toxin regions. In addition, the 15 amino acids, absolutely conserved in all the scorpion α-toxins described so far, are mostly located in molecular interior, which may be involved in structural constraints for stabilizing the CSαβ fold in evolution of these molecules- Four hot spot mutation sites in the molecular surface are found to distribute in the putative functional regions of a-toxins, suggestingScorpion a-toxins are a family of toxic proteins with similar scaffold, but possess divergent pharmacological properties. Analysis of cDNA sequences reveals that the numbers of nucleotide substitutions per site (K) for 5' and 3' UTRs are smaller than those per synonymous site (Ks) for the mature peptide-coding sequences, whereas the numbers of nucleotide substitutions per nonsynonymous site (Ka) are close to or larger than Ks values for relevant pairs of cDNAs. These results, together with phylogenetic analysis, indicate that scorpion α-toxins have evolved by accelerated substitutions in the mature toxin regions. In addition, the 15 amino acids, absolutely conserved in all the scorpion α-toxins described so far, are mostly located in molecular interior, which may be involved in structural constraints for stabilizing the CSαβ fold in evolution of these molecules- Four hot spot mutation sites in the molecular surface are found to distribute in the putative functional regions of a-toxins, suggesting that positive Darwinian selection drives the accelerated evolution of scorpion a-toxins. These findings reasonably explain the relationship between three-dimensional structure conservation and functional divergence of scorpion a-toxins and are of important value in guiding us in our engineering experiments to obtain higher affinity ligands to Na channels.

关 键 词：SCORPION α-toxins cDNA ACCELERATED evolution functional divergence. 

分 类 号：Q58[生物学—生物化学]