An In Silico Study of the Ros/MucR Protein Family Distribution and Its Structural Properties across Bacterial and Eukaryotic Lineages

The Ros/MucR protein family represents a group of prokaryotic zinc-finger transcriptional regulators involved in gene regulation, virulence, and host–microbe interactions. Although structurally characterized in α-proteobacteria, the evolutionary distribution and structural conservation of Ros homologs across broader taxonomic lineages remain unclear. In this study, we performed a large-scale comparative analysis of Ros/MucR homologs across bacterial and eukaryotic taxa using sequence homology searches, multiple sequence alignment, phylogenetic reconstruction, structural modeling, and statistical analysis. A total of 1,840 homologous sequences were identified, with α-proteobacteria showing the highest sequence conservation. Predicted zinc-coordination patterns varied substantially among taxonomic groups, yet structural comparisons indicated that the C-terminal DNA-binding domain remained broadly conserved despite sequence divergence. In contrast, δ-proteobacterial homologs exhibited increased sequence and structural divergence. Analysis of the N-terminal domain revealed that residues associated with oligomerization are strongly conserved in α-proteobacteria but more variable in other lineages, although hydrophobic character at these positions is often retained. Phylogenetic analysis showed a polyphyletic distribution of homologs across taxa, with eukaryotic Ros-like sequences appearing in multiple regions of the tree. Overall, these findings indicate that Ros/MucR proteins combine evolutionary flexibility with structural resilience, maintaining a conserved DNA-binding architecture despite diversification of predicted zinc-coordination residues and oligomerization-related features. This work provides a comparative evolutionary framework for understanding structural conservation and functional diversification within the Ros/MucR protein family.