title: Evolutionary dynamics of Polynucelotide phosphorylases.
abstract: Polynucleotide phosphorylase (PNPase) is an evolutionarily conserved 3'→5' phosphate-dependent exoribonucease belonging to the PDX family of proteins. It consists of two catalytic RNase PH domains (PNP1 and PNP2), an α-helical domain and two RNA-binding domains. The PNP1 and PNP2 domains share substantial sequence and structural homology with RNase PH (RPH), which is another PDX family member found in all the three major kingdoms of life, suggesting that these three domains originated from a common ancestor. Phylogenetic analysis (based on the PNPase/RNase PH sequence information for 43 vertebrate taxa) shows that PNP2 and RPH are sister taxa which arose through duplication of the ancestral PNP1 domain. Also, all three domains (PNP1, PNP2 and RPH), along with the KH and S1 domains have undergone significant and directional sequence change, as determined by branch and site-specific dN/dS analyses. In general, codons that show dN/dS ratios that are significantly greater than 1.0 are outside the ordered regions (α-helices and β-sheets) of these protein domains. In addition, sites that have been selected for mutagenesis in these proteins lie embedded in regions where there is a preponderance of codons with dN/dS values that are not significantly different from 0.0. Overall, this report is an attempt to further our understanding of the evolutionary history of these three protein domains, and define the evolutionary events that led to their refinement in the vertebrate lineage leading to mammals.
authors: Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States; VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States.
authors: Upneet K
authors: UK
authors: Sokhi
authors: American Museum of Natural History, New York University, New York, NY, United States. Electronic address: desalle@amnh.org.
authors: Rob
authors: R
authors: DeSalle
authors: Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States; VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States.
authors: Manny D
authors: MD
authors: Bacolod
authors: Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States; VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States.
authors: Swadesh K
authors: SK
authors: Das
authors: Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States; VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States.
authors: Santanu
authors: S
authors: Dasgupta
authors: Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States; VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States; VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States.
authors: Devanand
authors: D
authors: Sarkar
authors: Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States; VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States; VCU Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States. Electronic address: pbfisher@vcu.edu.
authors: Paul B
authors: PB
authors: Fisher
mesh_terms: D000818:Animals; D020134:Catalytic Domain / Q000235:genetics; D003062:Codon / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D019143:Evolution, Molecular; D010802:Phylogeny; D011117:Polyribonucleotide Nucleotidyltransferase / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D017433:Protein Structure, Secondary; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D003062:Codon; D011117:Polyribonucleotide Nucleotidyltransferase
keywords: Positive selection; Purifying selection; dN/dS ratio