GENOMIC SEQUENCES ENCODING THE ACIDIC AND BASIC SUBUNITS OF MOJAVE TOXIN - UNUSUALLY HIGH SEQUENCE IDENTITY OF NONCODING REGIONS

Mojave toxin (Mtx) is a heterodimeric, neurotoxic phospholipase A(2) ( PLA(2)) found in the venom of the Mojave rattlesnake, Crotalus scutula tus scutulatus, and is characteristic of all rattlesnake presynaptic n eurotoxins. This paper describes the isolation and nucleotide (nt) seq uence of the genomic clones encoding both the non-neurotoxic, nonenzym atic acidic subunit (Mtx-a) and the toxic, PLA(2)-active basic subunit (Mtx-b), and compares their structures. Both cloned genes shared virt ually identical overall organization, with four exons separated by thr ee introns, which were inserted in the same relative positions of the genes' coding regions. The exon/intron structure was similar to that r eported for mammalian PLA(2) genes. Most remarkable was the high degre e of nt sequence identity between Mtx-a and Mtx-b. While the exons sha red about 70% identity, the introns were greater than 90% identical an d 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 stron g selection on the nt sequence of the non-coding regions during this e volutionary process. This is the first report of genomic sequences of PLA(2)-like proteins from snakes.