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Abstract
A new member of the human RNase A superfamily is reported. Identified in the human genome assembly as LOC 390443, this locus is located 128 kb telomeric to the established RNase A gene family cluster on chromosome 14q11.2. The amino acid sequence of this locus is sufficiently similar to the eight previously identified gene family members to warrant a designation as RNase 9. RNase 9 is expressed in a wide range of human tissues. In addition, a 30-amino acid sequence lying between a 26-amino acid putative signal peptide and the last 148 amino acids that align with the other RNases A is not seen in other members of the RNase A superfamily in any species. Nucleotide and amino acid sequences of RNase 9 in 13 nonhuman primate species were determined and indicate several conserved sites but, also, an excess of nonsynonymous substitutions, about one-third of which are radical substitutions. This suggests that RNase 9, similar to several other human RNases A, has been under diversifying selection in the primates. Data from the mouse and rat genomes indicate that RNase 9 is also present in rodents, thus making it older than most of the established members of the human RNase A superfamily. Many of the human RNases A have been shown to have antimicrobial, antiviral, or antiparasitic functions involved in host-defense mechanisms. The features of RNase 9 described here suggest that it, too, may be involved in host defense and that it, along with the rest of the superfamily, may prove to have played an important role in anthropoid evolution.
KEY WORDS: RIBONUCLEASES, RNASE A SUPERFAMILY, HOST-DEFENSE MECHANISMS, DIVERSIFYING SELECTION, PRIMATES, ANTHROPOID EVOLUTION.
The ribonuclease (RNase) A gene family is the only vertebrate-specific superfamily known to encode proteins with enzymatic function (Lander et al. 2001). To date, eight members of the superfamily have been identified in the human genome, all located in a 375-kb region of chromosome 14q11.2 (Zhang et al. 2002). The encoded enzymes exhibit diverse expression patterns, varying catalytic activities against specific RNA substrates, and a variety of physiologic functions (Zhang et al. 2002, 2003). Recent studies of a number of these proteins have shown that they are involved in antimicrobial, antiviral, or antiparasitic host-defense mechanisms (Harder and Schroder 2002; Rosenberg and...