Abstract
Several genes in Gram-negative bacteria encoding outer membrane proteins (OMPs) have been reported to show patterns of mosaic evolution featured by a mixture of negative selection and local recombination. Here, we improved a strategy and applied it to screen OMPs under mosaic evolution in Escherichia coli at the genome level. In total, 21 OMP families, including 16 new ones, were detected with the typical patterns of mosaic evolution. An absolute majority of the protein families are conserved in E. coli for the composition, genomic loci, and the overall structures. Highly variable regions (HVRs) can be recognized, which are frequently located extracellularly within the protruding loops. There is only a limited number of major HVR sequence types, within which positively selected sites can be detected occassionally. Based on the simulated results of multiple models, the OMPs under mosaic evolution are often with good antigenicity, with HVRs of various sequence types coinciding with the B-cell epitopes of the strongest immunogenicity. The study further broadened our understanding of the characteristics of mosaic evolution and the functions of OMPs in Gram-negative bacteria, laying an important foundation for their potential translational applications.IMPORTANCEIt is important to understand the evolutionary mechanisms of bacterial OMP-encoding genes, which would facilitate the development of anti-bacterial reagents. This study made the first genome-wide screening of bacterial OMPs under mosaic evolution and increased the list of candidate OMP families by threefold in E. coli, far more than we expected. The study further confirmed the hypothesis about the evolutionary, micro-evolutionary, and structural features of these OMPs and facilitated the functional theory of mosaic evolution. Moreover, the findings of limited HVR sequence types and strong immunogenicity of HVRs paved an important foundation for the application of these OMPs and their HVRs in the development of antibodies or other antibacterial treatment.