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Network Analysis of RAD51 Proteins in Metazoa and the Evolutionary Relationships With Their Archaeal Homologs.

ABSTRACT: The RAD51 (DNA repair protein RAD51) recombinases are essential for homologous recombination, DNA repair, and genome stability. Overexpression of RAD51 proteins has been observed in many cancer cells, such as thyroid carcinoma, breast cancer, pancreatic cancer, and others. In Metazoa, there are multiple members of RAD51 (RAD51, RAD51B, RAD51C, RAD51D, DMC1) (DNA meiotic recombinase 1), XRCC2 (X-ray repair cross-complementing 2), and XRCC3. In this study, we used a protein sequence similarity network (SSN) to analyze the evolutionary relationship within this protein family. The SSN based on the RAD51 proteins from Metazoa indicated that there are several proteins that have yet to be functionally defined. The SSN based on the distribution of the proteins supports the hypothesis that horizontal gene transfer plays an important role in the evolution of RAD51 proteins. Multiple sequence alignments with structural information revealed that the amino acid residues for ATP and Mg²⁺ are highly conserved. The seven RAD51 proteins in humans are under different selective pressure: RAD51 and DMC1 are under stringent negative selection, while other proteins are subject to relatively relaxed negative selection. Furthermore, the expression levels of the seven genes in different tissues showed that the genes in the same cluster in the phylogenetic tree showed similar expression profiles. Finally, the SSN based on the RAD51 proteins from both eukaryotes and prokaryotes suggested that the eukaryotic RAD51 recombinases share a common ancestor with the archaeal homologs, but XRCC2 may have a different origin. These findings expand the understanding of the evolution and diversity of RAD51 recombinases in Metazoa.

SUBMITTER: Jiang S

PROVIDER: S-EPMC6168637 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Archaea and particularly hyperthermophilic crenarchaea are hosts to many unusual viruses with diverse virion shapes and distinct gene compositions. As is typical of viruses in general, there are no universal genes in the archaeal virosphere. Therefore, to obtain a comprehensive picture of the evolutionary relationships between viruses, network analysis methods are more productive than traditional phylogenetic approaches. Here we present a comprehensive comparative analysis of genomes and proteomes from all currently known taxonomically classified and unclassified, cultivated and uncultivated archaeal viruses. We constructed a bipartite network of archaeal viruses that includes two classes of nodes, the genomes and gene families that connect them. Dissection of this network using formal community detection methods reveals strong modularity, with 10 distinct modules and 3 putative supermodules. However, compared to similar previously analyzed networks of eukaryotic and bacterial viruses, the archaeal virus network is sparsely connected. With the exception of the tailed viruses related to bacteriophages of the order Caudovirales and the families Turriviridae and Sphaerolipoviridae that are linked to a distinct supermodule of eukaryotic and bacterial viruses, there are few connector genes shared by different archaeal virus modules. In contrast, most of these modules include, in addition to viruses, capsidless mobile elements, emphasizing tight evolutionary connections between the two types of entities in archaea. The relative contributions of distinct evolutionary origins, in particular from nonviral elements, and insufficient sampling to the sparsity of the archaeal virus network remain to be determined by further exploration of the archaeal virosphere.ImportanceViruses infecting archaea are among the most mysterious denizens of the virosphere. Many of these viruses display no genetic or even morphological relationship to viruses of bacteria and eukaryotes, raising questions regarding their origins and position in the global virosphere. Analysis of 5,740 protein sequences from 116 genomes allowed dissection of the archaeal virus network and showed that most groups of archaeal viruses are evolutionarily connected to capsidless mobile genetic elements, including various plasmids and transposons. This finding could reflect actual independent origins of the distinct groups of archaeal viruses from different nonviral elements, providing important insights into the emergence and evolution of the archaeal virome.

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Network Analysis of RAD51 Proteins in Metazoa and the Evolutionary Relationships With Their Archaeal Homologs.

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