EXPRESSION OF THE ALPHA(1)-PROTEINASE INHIBITOR GENE FAMILY DURING EVOLUTION OF THE GENUS MUS

alpha(1)-Proteinase inhibitors (alpha(1)-PIs) are members of the serpi n superfamily of proteinase inhibitors, and are important in the maint enance of homeostasis in a wide variety of animal taxa. Previous studi es have shown that in mice (genus Mus), evolution of alpha(1)-PIs is c haracterized by gene amplification, region-specific concerted evolutio n, and rapid accumulation of amino acid substitutions. The latter occu rs 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 methi onine in so-called orthodox alpha(1)-PIs and an amino acid other than methionine in unorthodox alpha(1)-PIs, is a primary determinant of inh ibitor specificity. In the present study, we find that the expression of mRNAs encoding unorthodox alpha(1)-PIs is polymorphic within Mus sp ecies, i.e., among individuals or inbred strains. This is in striking contrast to mRNAs that encode orthodox alpha(1)-PIs, whose concentrati ons are relatively invariant. The intraspecies variations in mRNA expr ession represent polymorphisms in the structure of the alpha(1)-PI gen e family. The results, taken together with previously described aspect s of alpha(1)-PI evolution, indicate that the dissimilar levels of pol ymorphism exhibited by orthodox and unorthodox alpha(1)-PIs, which lik ely have distinct physiological functions, may reflect different level s of selective constraint. The significance of this finding to the evo lution of gene families is discussed.