title: Rapid evolution of the ribonuclease A superfamily: adaptive expansion of independent gene clusters in rats and mice.
abstract: The two eosinophil ribonucleases, eosinophil-derived neurotoxin (EDN/RNase 2) and eosinophil cationic protein (ECP/RNase 3), are among the most rapidly evolving coding sequences known among primates. The eight mouse genes identified as orthologs of EDN and ECP form a highly divergent, species-limited cluster. We present here the rat ribonuclease cluster, a group of eight distinct ribonuclease A superfamily genes that are more closely related to one another than they are to their murine counterparts. The existence of independent gene clusters suggests that numerous duplications and diversification events have occurred at these loci recently, sometime after the divergence of these two rodent species ( approximately 10-15 million years ago). Nonsynonymous substitutions per site (d(N)) calculated for the 64 mouse/rat gene pairs indicate that these ribonucleases are incorporating nonsilent mutations at accelerated rates, and comparisons of nonsynonymous to synonymous substitution (d(N) / d(S)) suggest that diversity in the mouse ribonuclease cluster is promoted by positive (Darwinian) selection. Although the pressures promoting similar but clearly independent styles of rapid diversification among these primate and rodent genes remain uncertain, our recent findings regarding the function of human EDN suggest a role for these ribonucleases in antiviral host defense.
authors.affiliation: Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 10 Bethesda, MD 20892, USA.
authors.forename: N A
authors.initials: NA
authors.lastname: Singhania
authors.forename: K D
authors.initials: KD
authors.lastname: Dyer
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: M S
authors.initials: MS
authors.lastname: Deming
authors.forename: C A
authors.initials: CA
authors.lastname: Bonville
authors.forename: J B
authors.initials: JB
authors.lastname: Domachowske
authors.forename: H F
authors.initials: HF
authors.lastname: Rosenberg
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D017124:Conserved Sequence / Q000235:genetics; D019143:Evolution, Molecular; D020131:Genes, Duplicate / Q000235:genetics; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D010802:Phylogeny; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D012259:Ribonuclease, Pancreatic / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D012641:Selection, Genetic; D016415:Sequence Alignment; D013997:Time Factors
chemical_list: D012333:RNA, Messenger; D012259:Ribonuclease, Pancreatic