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Ancient gene duplications in RNA viruses revealed by protein tertiary structure comparisons.

ABSTRACT: To date only a handful of duplicated genes have been described in RNA viruses. This shortage can be attributed to different factors, including the RNA viruses with high mutation rate that would make a large genome more prone to acquire deleterious mutations. This may explain why sequence-based approaches have only found duplications in their most recent evolutionary history. To detect earlier duplications, we performed protein tertiary structure comparisons for every RNA virus family represented in the Protein Data Bank. We present a list of thirty pairs of possible paralogs with <30 per cent sequence identity. It is argued that these pairs are the outcome of six duplication events. These include the α and β subunits of the fungal toxin KP6 present in the dsRNA Ustilago maydis virus (family Totiviridae), the SARS-CoV (Coronaviridae) nsp3 domains SUD-N, SUD-M and X-domain, the Picornavirales (families Picornaviridae, Dicistroviridae, Iflaviridae and Secoviridae) capsid proteins VP1, VP2 and VP3, and the Enterovirus (family Picornaviridae) 3C and 2A cysteine-proteases. Protein tertiary structure comparisons may reveal more duplication events as more three-dimensional protein structures are determined and suggests that, although still rare, gene duplications may be more frequent in RNA viruses than previously thought. Keywords: gene duplications; RNA viruses.

SUBMITTER: Cisneros-Martinez AM

PROVIDER: S-EPMC7967035 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundRhodobacter sphaeroides 2.4.1 is a metabolically versatile organism that belongs to ?-3 subdivision of Proteobacteria. The present study was to identify the extent, history, and role of gene duplications in R. sphaeroides 2.4.1, an organism that possesses two chromosomes.ResultsA protein similarity search (BLASTP) identified 1247 orfs (~29.4% of the total protein coding orfs) that are present in 2 or more copies, 37.5% (234 gene-pairs) of which exist in duplicate copies. The distribution of the duplicate gene-pairs in all Clusters of Orthologous Groups (COGs) differed significantly when compared to the COG distribution across the whole genome. Location plots revealed clusters of gene duplications that possessed the same COG classification. Phylogenetic analyses were performed to determine a tree topology predicting either a Type-A or Type-B phylogenetic relationship. A Type-A phylogenetic relationship shows that a copy of the protein-pair matches more with an ortholog from a species closely related to R. sphaeroides while a Type-B relationship predicts the highest match between both copies of the R. sphaeroides protein-pair. The results revealed that ~77% of the proteins exhibited a Type-A phylogenetic relationship demonstrating the ancient origin of these gene duplications. Additional analyses on three other strains of R. sphaeroides revealed varying levels of gene loss and retention in these strains. Also, analyses on common gene pairs among the four strains revealed that these genes experience similar functional constraints and undergo purifying selection.ConclusionsAlthough the results suggest that the level of gene duplication in organisms with complex genome structuring (more than one chromosome) seems to be not markedly different from that in organisms with only a single chromosome, these duplications may have aided in genome reorganization in this group of eubacteria prior to the formation of R. sphaeroides as gene duplications involved in specialized functions might have contributed to complex genomic development.

Project description:RNA junctions are secondary-structure elements formed when three or more helices come together. They are present in diverse RNA molecules with various fundamental functions in the cell. To better understand the intricate architecture of three-dimensional (3D) RNAs, we analyze currently solved 3D RNA junctions in terms of base-pair interactions and 3D configurations. First, we study base-pair interaction diagrams for solved RNA junctions with 5 to 10 helices and discuss common features. Second, we compare these higher-order junctions to those containing 3 or 4 helices and identify global motif patterns such as coaxial stacking and parallel and perpendicular helical configurations. These analyses show that higher-order junctions organize their helical components in parallel and helical configurations similar to lower-order junctions. Their sub-junctions also resemble local helical configurations found in three- and four-way junctions and are stabilized by similar long-range interaction preferences such as A-minor interactions. Furthermore, loop regions within junctions are high in adenine but low in cytosine, and in agreement with previous studies, we suggest that coaxial stacking between helices likely forms when the common single-stranded loop is small in size; however, other factors such as stacking interactions involving noncanonical base pairs and proteins can greatly determine or disrupt coaxial stacking. Finally, we introduce the ribo-base interactions: when combined with the along-groove packing motif, these ribo-base interactions form novel motifs involved in perpendicular helix-helix interactions. Overall, these analyses suggest recurrent tertiary motifs that stabilize junction architecture, pack helices, and help form helical configurations that occur as sub-elements of larger junction networks. The frequent occurrence of similar helical motifs suggest nature's finite and perhaps limited repertoire of RNA helical conformation preferences. More generally, studies of RNA junctions and tertiary building blocks can ultimately help in the difficult task of RNA 3D structure prediction.

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Ancient gene duplications in RNA viruses revealed by protein tertiary structure comparisons.

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