Mouse eosinophil-associated ribonucleases: a unique subfamily expressed during hematopoiesis

A unique family of ribonucleases was identified by exhaustive screening of genomic and cDNA libraries using a probe derived from a gene encoding a rib onuclease stored in the mouse eosinophil secondary granule. This family con tains at least 13 genes, which encode ribonucleases, and two potential pseu dogenes. The conserved sequence identity among these genes (similar to 70%) , as well as the isolation/purification of these ribonucleases from eosinop hil secondary granules, has led us to conclude that these genes form a uniq ue clade in the mouse that we have identified as the Ear ((E) under bar osi nophil-(a) under bar ssociated (r) under bar ibonuclease) gene family. Anal yses of the nucleotide substitutions that have occurred among these ribonuc lease genes reveal that duplication events within this family have been epi sodic, occurring within three unique periods during the past 18 x 10(6) yea rs. Moreover, comparisons of nonsynonymous (K-a) vs. synonymous (K-s) rates of nucleotide substitution show that although these genes conserve residue s necessary for RNase activity, selective evolutionary pressure(s) exist su ch that acquired amino acid changes appear to be advantageous. The selectiv e advantage of these amino acid changes is currently unclear, but the occur rence of this phenomenon in both the mouse and the human highlights the imp ortance of these changes for Ear and, therefore, eosinophil effector functi on(s).