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 alpha-1-antitrypsin) with a molecular mass of 56 kDa was purified from plasma of the Mongolian gerbil, Meriones unguiculatus, to apparent homogeneity. It inhibited trypsin, chymotrypsin, elastase, and plasmin, but not kallikrein or thrombin. Eight cDNA clones coding for this protein were isolated from a liver cDNA library and sequenced. They contained the same coding regions consisting of a 24-residue signal peptide and a 382-residue mature protein. The reactive site sequence (P3-P3) was 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, constructed on the basis of the synonymous substitution rate, shows (i) that the reactive site region is highly conserved as compared to the other part of the molecule, which contrasts with the generally accepted view that 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 traditional taxonomy based on the morphology. In the present tree, the guinea pig joins the lagomorph (rabbit), and is rather widely separated from the myomorph branch. The result, however, supports the recent hypothesis 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 ordinal status distinct from the rodents.
Department of Biochemistry, Kinki University School of Medicine, Osaka.
K
K
Goto
Y
Y
Suzuki
K
K
Yoshida
K
K
Yamamoto
H
H
Sinohara
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics*; D005849:Gerbillinae / Q000097:blood*; D008969:Molecular Sequence Data; D015183:Restriction Mapping; D000515:alpha 1-Antitrypsin / Q000235:genetics / Q000378:metabolism*
D018076:DNA, Complementary; D000515:alpha 1-Antitrypsin