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Evolutionary mechanisms of origins of new gene function have been a subject of long-standing debate. Here we report a convincing case in which positive Darwinian selection operated at the molecular level during the evolution of novel function by gene duplication. The genes for eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) in(More)
The mammalian RNase A superfamily comprises a diverse array of ribonucleolytic proteins that have a variety of biochemical activities and physiological functions. Two rapidly evolving RNases of higher primates are of particular interest as they are major secretory proteins of eosinophilic leukocytes and have been found to possess anti-pathogen activities in(More)
RNase A (bovine pancreatic RNase) is the founding member an extensive family of divergent proteins that share specific elements of sequence homology, a unique disulfide-bonded tertiary structure, and the ability to hydrolyze polymeric RNA. Among the more intriguing and perhaps counterintuitive findings, at the current state of the art, the connection(More)
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.(More)
Here we report on the expression and function of RNase 7, one of the final RNase A superfamily ribonucleases identified in the human genome sequence. The human RNase 7 gene is expressed in various somatic tissues including the liver, kidney, skeletal muscle and heart. Recombinant RNase 7 is ribonucleolytically active against yeast tRNA, as expected from the(More)
We have isolated a unique genomic fragment encoding human ribonuclease 4 (RNase 4) of the mammalian ribonuclease gene family, whose members include pancreatic ribonuclease, eosinophil-derived neurotoxin, eosinophil cationic protein and angiogenin. We have determined that the coding sequence of RNase 4 resides on a single exon found on human chromosome 14.(More)
Although the complete genome sequences of over 50 representative species have revealed the many duplicated genes in all three domains of life, the roles of gene duplication in organismal adaptation and biodiversity are poorly understood. In addition, the evolutionary forces behind the functional divergence of duplicated genes are often unknown, leading to(More)
Eosinophil-derived neurotoxin (EDN) is an eosinophil granule-derived secretory protein with ribonuclease and antiviral activity. We have previously shown that EDN can induce the migration and maturation of dendritic cells (DCs). Here, we report that EDN can activate myeloid DCs by triggering the Toll-like receptor (TLR)2-myeloid differentiation factor 88(More)
We have devised an ex vivo culture system which generates large numbers of eosinophils at high purity (>90%) from unselected mouse bone marrow progenitors. In response to 4 days of culture with recombinant mouse FLT3-L and recombinant mouse stem cell factor followed by recombinant mouse IL-5 alone thereafter, the resulting bone marrow-derived eosinophils(More)
An improved understanding of the evolution of gene function at the molecular level may provide significant insights into the origin of biological novelty and adaptation. With the approach of ancestral protein reconstruction, we here address the question of how a dramatically enhanced ribonucleolytic activity and the related antiviral activity evolved in a(More)