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Nucleic Acids Research, 2002, Vol. 30, No. 5 1169-1175
© 2002 Oxford University Press

RNase 8, a novel RNase A superfamily ribonuclease expressed uniquely in placenta

Jianzhi Zhang1,2,*, Kimberly D. Dyer1 and Helene F. Rosenberg1

1Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA and 2Department of Ecology and Evolutionary Biology and Department of Molecular, Cellular and Developmental Biology, University of Michigan, MI 48109, USA

We report the identification and characterization of the gene encoding the eighth and final human ribonuclease (RNase) of the highly diversified RNase A superfamily. The RNase 8 gene is linked to seven other RNase A superfamily genes on chromosome 14. It is expressed prominently in the placenta, but is not detected in any other tissues examined. Phylogenetic analysis suggests that RNase 7 is the closest relative of RNase 8 and that the pair likely resulted from a recent gene duplication event in primates. Further analysis reveals that the RNase 8 gene has incorporated non-silent mutations at an elevated rate (1.3 x 10–9 substitutions/site/year) and that orthologous RNase 8 genes from 6 of 10 primate species examined have been deactivated by frameshifting deletions or point mutations at crucial structural or catalytic residues. The ribonucleolytic activity of recombinant human RNase 8 is among the lowest of members of this superfamily and it exhibits neither antiviral nor antibacterial activities characteristic of some other RNase A ribonucleases. The rapid evolution, species-limited deactivation and tissue-specific expression of RNase 8 suggest a unique physiological function and reiterates the evolutionary plasticity of the RNase A superfamily.

* To whom correspondence should be addressed at: Departments of Ecology and Evolutionary Biology and Molecular, Cellular and Developmental Biology, University of Michigan, 3003 Natural Sciences Building, 830 North University Avenue, Ann Arbor, MI 48109, USA. Tel: +1 734 763 0527; Fax: +1 734 763 0544; Email: jianzhi{at}umich.edu


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