ACCELERATED EVOLUTION OF SNAKE-VENOM PHOSPHOLIPASE A(2) ISOZYMES FOR ACQUISITION OF DIVERSE PHYSIOLOGICAL FUNCTIONS

The nucleotide sequences of two cDNAs and four genes encoding Trimeres urus gramineus venom gland phospholipase A(2) (PLA(2)) isozymes were d etermined and compared internally and externally with those encoding T rimeresurus flavoviridis venom gland PLA(2) isozymes. It was revealed that the protein-coding regions are much more diversified than the 5' and 3' untranslated regions (UTRs) and the introns except for the sign al peptide domain. The numbers of nucleotide substitutions per site (K -N) for the UTRs and the introns were approximately one-quarter of the numbers of nucleotide substitutions per synonymous site (K-s) for the protein-coding regions and were at the same level as the K-N value of T. gramineus and T. flavoviridis TATA box-binding protein (TBP) genes , indicating that the protein-coding regions of PLA(2) isozyme genes a re unusually variable and that the UTRs including the introns of venom gland PLA(2) isozyme genes have evolved at similar rate to those of n on-venomous genes. The numbers of nucleotide substitutions per non-syn onymous site (K-A) values were close to or larger than the K-s values for the protein-coding regions in venom gland PLA(2) isozyme genes, in dicating that the protein-coding regions of snake venom gland PLA(2) i sozyme genes have evolved via accelerated evolution. Furthermore, the evolutionary trees derived from the combined sequences of the 5' and 3 ' UTRs and the signal peptide domain of cDNAs were in accord with the consequences from taxonomy. In contrast, the evolutionary trees from t he mature protein-coding region sequences of cDNAs and from the amino acid sequences showed random patterns. Estimations of nucleotide diver gence of genes and the phylogenetic analysis reveal that snake venom g roup II PLA(2) isozyme genes have been evolving under adaptive pressur e to acquire new physiological activities. Copyright (C) 1996 Elsevier Science Ltd