Evolution of the rodent eosinophil-associated RNase gene family by rapid gene sorting and positive selection

The mammalian RNase A superfamily comprises a diverse array of ribonucleoly tic proteins that have a variety of biochemical activities and physiologica l functions. Two rapidly evolving RNases of higher primates are of particul ar interest as they are major secretory proteins of eosinophilic leukocytes and have been found to possess anti-pathogen activities in vitro. To under stand how these RNases acquired this function during evolution and to devel op animal models for the study of their functions in vivo, it is necessary to investigate these genes in many species. Here, we report the sequences o f 38 functional genes and 23 pseudogenes of the eosinophil-associated RNase (EAR) family from 5 rodent species. Our phylogenetic analysis of these gen es showed a clear pattern of evolution by a rapid birth-and-death process a nd gene sorting, a process characterized by rapid gene duplication and deac tivation occurring differentially among lineages. This process ultimately g enerates distinct or only partially overlapping inventories of the genes, e ven in closely related species. Positive Darwinian selection also contribut ed to the diversification of these EAR genes. The striking similarity betwe en the evolutionary patterns of the EAR genes and those of the major histoc ompatibility complex, immunoglobulin, and T cell receptor genes stands in s trong support of the hypothesis that host-defense and generation of diversi ty are among the primary physiological function of the rodent EARs. The dis covery of a large number of divergent EARs suggests the intriguing possibil ity that these proteins have been specifically tailored to fight against di stinct rodent pathogens.