title: Expression of the alpha 1-proteinase inhibitor gene family during evolution of the genus Mus.
abstract: alpha 1-Proteinase inhibitors (alpha 1-PIs) are members of the serpin superfamily of proteinase inhibitors, and are important in the maintenance of homeostasis in a wide variety of animal taxa. Previous studies have shown that in mice (genus Mus), evolution of alpha 1-PIs is characterized by gene amplification, region-specific concerted evolution, and rapid accumulation of amino acid substitutions. The latter occurs primarily in the reactive center, which is the region of the alpha 1-PI molecule that determines the inhibitor's specificity for target proteinases. The P1 residue within the reactive center, which is methionine in so-called orthodox alpha 1-PIs and an amino acid other than methionine in unorthodox alpha 1-PIs, is a primary determinant of inhibitor specificity. In the present study, we find that the expression of mRNAs encoding unorthodox alpha 1-PIs is polymorphic within Mus species, i.e., among individuals or inbred strains. This is in striking contrast to mRNAs that encode orthodox alpha 1-PIs, whose concentrations are relatively invariant. The intraspecies variations in mRNA expression represent polymorphisms in the structure of the alpha 1-PI gene family. The results, taken together with previously described aspects of alpha 1-PI evolution, indicate that the dissimilar levels of polymorphism exhibited by orthodox and unorthodox alpha 1-PIs, which likely have distinct physiological functions, may reflect different levels of selective constraint. The significance of this finding to the evolution of gene families is discussed.
authors.affiliation: Department of Biological Sciences, University of South Carolina, Columbia, South Carolina 29208-1801, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Goodwin
authors.forename: K W
authors.initials: KW
authors.lastname: Barbour
authors.forename: F G
authors.initials: FG
authors.lastname: Berger
mesh_terms: D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary; D019143:Evolution, Molecular; D005796:Genes; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics; D008969:Molecular Sequence Data; D009115:Muridae / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D013045:Species Specificity; D000515:alpha 1-Antitrypsin / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D012333:RNA, Messenger; D000515:alpha 1-Antitrypsin