A Phospholipase A 2 -Like Pseudogene Retaining the Highly Conserved Introns of Mojave Toxin and Other Snake Venom Group II PLA 2 S,but Having Different Exons

Mojave toxin is a neurotoxic, heterodimeric phospholipase A₂ (PLA₂) from the venom of the Mojave rattlesnake (Crotalus scutulatus scutulatus) and is characteristic of all rattlesnake presynaptic neurotoxins. Here, we describe a phospholipase A₂ pseudogene (ψ-Mtx) located 2,000 nucleotides upstream, and on the opposite DNA strand, from a gene for Mojave toxin acidic subunit (Mtx-a). The pseudogene lacks the first exon and a few segments of noncoding DNA found in functional snake venom PLA₂ genes, but does have the coding information for a complete PLA₂ protein. ψ-Mtx retains the unusual gene sequence similarity pattern found in functional viperid PLA₂ genes. When compared to genes from C. s. scutulatus and the Habu snake (Trimeresurus flavoviridus), ψ-Mtx shows strong conservation of nocoding regions and variable protein-coding regions. Although the nocoding regions of ψ-Mtx are conserved with respect to other viperid PLA₂ genes, the three exons code for a unique PLA₂-like protein similar in sequence to ammodytoxin b found in the venom of the western sand viper (Vipera ammodytes ammodytes). The structure of these genes suggests a common ancestor for all viperid PLA₂ genes. Phylogenetic analysis of ψ-Mtx, Mtx-a, Mtx-b, pgPLA 1a, and pgPLA 1b suggest that ψ-Mtx diverged from an ancestral sequence before the presumed gene duplication event leading to Mtx-a and Mtx-b. However, analysis of the basis of coding regions alone gives a conflicting result.