Patterns of divergence during evolution of alpha 1-proteinase inhibitors in mammals

alpha 1-Proteinase inhibitor (alpha 1-PI), a member of the serineproteinase inhibitor superfamily, has a primary role in controllingneutrophil elastase activity within the mammalian circulation. Severalstudies have indicated that the reactive center region of alpha 1-PI, theamino acid sequence of which is critical to recognition of and binding totarget proteinases, is highly divergent within and among species. Thisappears to be a consequence of accelerated rates of evolution that may havebeen driven by positive Darwinian selection. In order to examine this andother features of alpha 1-PI evolution in more detail, we have isolated andsequenced cDNAs representing alpha 1- PI mRNAs of the mouse species Mussaxicola and Mus minutoides and have compared these with a number of othermammalian alpha 1-PI mRNAs. Relative to other mammalian mRNAs, the extentof nonsynonymous substitution is generally high throughout the alpha 1-PImRNA molecule, indicating greater overall rates of amino acid substitution.Within and among mouse species, the 5'-half of the mRNA, but not the3'-half, has been homogenized by concerted evolution. Finally, the reactivecenter is under diversifying or positive Darwinian selection in muridrodents (rats, mice) and guinea pigs yet is under purifying selection inprimates and artiodactyls. The significance of these findings to alpha 1-PIfunction and the possible selective forces driving evolution of serpins ingeneral are discussed.