RIBONUCLEASE K6 - CHROMOSOMAL MAPPING AND DIVERGENT RATES OF EVOLUTION WITHIN THE RNASE-A GENE SUPERFAMILY

We have localized the gene encoding human RNase k6 to within similar t o 120 kb on the long (q) arm of chromosome 14 by HAPPY mapping. With t his information, the relative positions of the six human RNase A ribon ucleases that have been mapped to this locus can be inferred. To furth er our understanding of the individual lineages comprising the RNase A superfamily, we have isolated and characterized 10 novel genes orthol ogous to that encoding human RNase k6 from Great Ape, Old World, and N ew World monkey genomes. Each gene encodes a complete ORF with no less than 86% amino acid sequence identity to human RNase k6 with the eigh t cysteines and catalytic histidines (H-15 and H-123) and lysine (K-38 ) typically observed among members of the RNase A superfamily. interes ting trends include an unusually low number of synonymous substituions (K-s) observed among the New World monkey RNase k6 genes. When consid ering nonsilent mutations, RNase k6 is a relatively stable lineage, Wi th a nonsynonymous substitution rate of 0.40 x 10(-9) nonsynonymous su bstitutions/nonsynonymons site/year (ns/ns/yr). These results stand in contrast to those determined for the primate orthologs of the two clo sely related ribonucleases, the eosinophil-derived neurotoxin (EDN) an d eosinophil cationic protein (ECP), which have incorporated nonsilent mutations at very rapid rates (1.9 x 10(-9) and 2.0 x 10(-9) ns/ns/yr , respectively). The uneventful trends observed for RNase k6 serve to spotlight the unique nature of EDN and ECP and the unusual evolutionar y constraints to which these two ribonuclease genes must be responding .