Genetic organization of A chain and B chain of beta-bungarotoxin from Taiwan banded krait (Bungarus multicinctus) - A chain genes and B chain genes do not share a common origin

beta-Bungarotoxin, the main presynaptic neurotoxin purified from the venom of Bungarus multicinctus, consists of two dissimilar polypeptide chains, th e A chain and the B chain, cross-linked by an interchain disulfide bond. In this study, A and B chain genes isolated from the liver of B. multicinctus encoded the A and B chain precursors, respectively. Analyses of the coding regions of the A and B chain genes revealed that both consist of three exo ns and two introns. The sequences of all exon/intron junctions agree with t he GT/AG rule. However, sequence alignment and phylogenetic analysis did no t support that the evolution of A and B chain genes are closely related. Co mparative analysis of A chain genes with Viperinae and Crotalinae phospholi pase A(2) genes indicated that genetic divergence of the A chain and phosph olipase A(2)s was in accordance with their family. Moreover, evolutionary d ivergence of the intron and exon regions of the A chain, as observed for ph ospholipase A(2) genes, was not consistent. Noticeably, the transcription o f A and B chain genes may be regulated under different transcription factor s as revealed by analyses of their promoter sequences. In terms of the find ing that A and B chains are encoded separately by different genes, this str ongly supports the view that the intact beta-bungarotoxin molecules should be derived from the pairing of A and B chains after their mRNAs are transla ted.