Evolution of Tertiary Structure of Viral RNA Dependent Polymerases

Abstract

Viral RNA dependent polymerases (vRdPs) are present in all RNA viruses; unfortunately, their sequence similarity is too low for phylogenetic studies. Nevertheless, vRdP protein structures are remarkably conserved. In this study, we used the structural similarity of vRdPs to reconstruct their evolutionary history. The major strength of this work is in unifying sequence and structural data into a single quantitative phylogenetic analysis, using powerful a Bayesian approach.The resulting phylogram of vRdPs demonstrates that RNA-dependent DNA polymerases (RdDPs) of viruses within Retroviridae family cluster in a clearly separated group of vRdPs, while RNA-dependent RNA polymerases (RdRPs) of dsRNA and +ssRNA viruses are mixed together. This evidence supports the hypothesis that RdRPs replicating +ssRNA viruses evolved multiple times from RdRPs replicating +dsRNA viruses, and vice versa. Moreover, our phylogram may be presented as a scheme for RNA virus evolution. The results are in concordance with the actual concept of RNA virus evolution. Finally, the methods used in our work provide a new direction for studying ancient virus evolution.

Annotating Protein Functional Residues by Coupling High-Throughput Fitness Profile and Homologous-Structure Analysis

“…It consists of three major conserved domains (finger, palm, and thumb) and six motifs (pre-A/F and A to E) (20). Since canonical vRdRp functional residues of the PB1 protein are expected to be structurally conserved, they aligned well with other protein structures from the vRdRp family.…”

“…Twenty representative vRdRp structures were selected from positive single-stranded RNA (ssRNA) viruses, negative ssRNA viruses, and double-stranded RNA (dsRNA) virus families on the basis of previously stated criteria (20). Briefly, representative structures were selected from each of the Baltimore classes that encoded vRdRp, including positive ssRNA viruses ( Caliciviridae , Flaviviridae , Picornaviridae , Cystoviridae ), dsRNA viruses ( Birnaviridae , Cystoviridae , and Reoviridae ), and negative ssRNA viruses ( Bunyaviridae ) (62–81).…”

“…vRdRps probably evolved from a common ancestor (100). Although their sequence identity is ~20%, they have adopted similar structural domains and use similar catalytic mechanisms (20). Throughout evolution, different proteins also evolved diverse functions to satisfy the needs of specific organisms.…”

Putative DNA-dependent RNA polymerase in Mitochondrial Plasmid of Paramecium caudatum Stock GT704

“…In linear plasmids, DNA polymerase and RNAP each is encoded by one single plasmid, or encoded by different plasmid if there are more than one plasmids in mitochondria (Cermakian et al 1997).…”

“…In this group of RNAP, a number of conserved motifs have been identified (Chan et al 1991). Cermakian et al (1997) states that motif X (INSLEA: Ile-Asn-Ser-Leu-Glu-Ala in pGT704-2.8) resides in the nucleotides 783e788 while motif XI (IHDCF: Ile-His-Asp-Cys-Phe) resides in the nucleotides 810e814. Considering the length of pGT704-2.8 as 2.8 indicates that the ORF is located in the center.…”