A phospholipase A2-like pseudogene retaining the highly conserved introns of Mojave toxin and other snake venom group II PLA2s, but having different exons.

Abstract

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 (psi-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. psi-Mtx retains the unusual gene sequence similarity pattern found in functional viperid PLA2 genes. When compared to genes from C. s. scutulatus and the Hahn snake (Trimeresurus flavoviridus), psi-Mtx shows strong conservation of nocoding regions and variable protein-coding regions. Although the nocoding regions of psi-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 psi-Mtx, Mtx-a, Mtx-b, pgPLA 1a, and pgPLA 1b suggest that psi-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.