Genomic sequences encoding the acidic and basic subunits of Mojave toxin: unusually high sequence identity of...

Mojave toxin (Mtx) is a heterodimeric, neurotoxic phospholipase A2 (PLA2) found in the venom of the Mojave rattlesnake, Crotalus scutulatus scutulatus, and is characteristic of all rattlesnake presynaptic neurotoxins. This paper describes the isolation and nucleotide (nt) sequence of the genomic clones encoding both the non-neurotoxic, non-enzymatic acidic subunit (Mtx-a) and the toxic, PLA2-active basic subunit (Mtx-b), and compares their structures. Both cloned genes shared virtually identical overall organization, with four exons separated by three introns, which were inserted in the same relative positions of the genes' coding regions. The exon/intron structure was similar to that reported for mammalian PLA2 genes. Most remarkable was the high degree of nt sequence identity between Mtx-a and Mtx-b. While the exons shared about 70% identity, the introns were greater than 90% identical and the 5' and 3' untranslated and flanking regions were greater than 95% identical. These findings support our earlier suggestion [Aird et al., Biochemistry 24 (1985) 7054-7058] that the genes coding for the two subunits arose from a common ancestor. There has clearly been a strong selection on the nt sequence of the non-coding regions during this evolutionary process. This is the first report of genomic sequences of PLA2-like proteins from snakes.