PLASMA ALPHA-1-ANTIPROTEINASE FROM THE MONGOLIAN GERBIL, MERIONES-UNGUICULATUS - ISOLATION, PARTIAL CHARACTERIZATION, SEQUENCING OF CDNA, AND IMPLICATIONS FOR MOLECULAR EVOLUTION

alpha-1-Antiproteinase (also called alpha-1-proteinase inhibitor or al pha-1-antitrypsin) with a molecular mass of 56 kDa was purified from p lasma of the Mongolian gerbil, Meriones unguiculatus, to apparent homo geneity. It inhibited trypsin, chymotrypsin, elastase, and plasmin, bu t not kallikrein or thrombin. Eight cDNA clones coding for this protei n were isolated from a liver cDNA library and sequenced. They containe d the same coding regions consisting of a 24-residue signal peptide an d a 382-residue mature protein. The reactive site sequence (P3-P'3) wa s Val-Pro-Met-Ser-Ile-Pro, characteristic of alpha-1-antiproteinase of orthodox type [Suzuki, Y. et al. (1991) J. Biol. Chem. 266, 928-932]. A molecular phylogenetic tree of 11 orthologous inhibitors, construct ed on the basis of the synonymous substitution rate, shows (i) that th e reactive site region is highly conserved as compared to the other pa rt of the molecule, which contrasts with the generally accepted view t hat the reactive site region of serpins is strongly hypervariable, and (ii) that the myomorphs (gerbil, rat, and two species of mouse, i.e. Mus domesticus and Mus caroli) and the caviomorph (guinea pig) fail to consist of a monophyletic order, which also contradicts the tradition al taxonomy based on the morphology. In the present tree, the guinea p ig joins the lagomorph (rabbit), and is rather widely separated from t he myomorph branch. The result, however, supports the recent hypothesi s based on the molecular evolution of several other proteins that the guinea pig does not belong to the same order as the myomorph, and the caviomorphs should be elevated in taxonomic rank and conferred an ordi nal status distinct from the rodents.