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.
Highlights
Homologous recombination (HR), the exchange of DNA strands of similar or identical nucleotide sequence, is essential to cell division in eukaryotes, including protists, fungi, plants, and animals
For a global analysis of the RAD51 protein family in Metazoa, the sequences of these genes were retrieved from the InterPro database1 (Mitchell et al, 2015)
The values for the seven genes were different: the dN/dS values for both RAD51 and DMC1 were
Summary
Homologous recombination (HR), the exchange of DNA strands of similar or identical nucleotide sequence, is essential to cell division in eukaryotes, including protists, fungi, plants, and animals. As the e-value cut-off was decreased to 10−30, human RAD51D was further separated from the cluster, but other proteins from humans (RAD51A, RAD51B, RAD51C, DMC1, and XRCC3) were still grouped together. RAD51A and DMC1 were close to each other, indicating that they share high identity in the protein sequence, and they were duplicated from the same ancestor.
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