Deciphering gene redundancy in prokaryotic genomes provides evolutionary insights for pathogenicity and its roles in clinical infections

Gene redundancy, increasing gene dosage and functional diversity, remains understudied regarding its roles in evolution and clinical infections. Exploring 22,310 prokaryotic genomes with our custom pipeline, we found that redundant genes, though less frequent than in eukaryotes, are widespread and mainly linked to niche specialization. Evolutionary analyses delineated a propensity for gene redundancy expansion with increasing phylogenetic distance, with pathogens accumulating more redundancy than non-pathogens. Redundant genes are always co-duplicated with translation initiation signals and potentially preserve functionality. Time series examining 69 Acinetobacter baumannii isolates from multi-sites in severely infected patients, we identified redundant alcohol dehydrogenase genes and translation initiation signals, introduced by gene islands, as advantageous for invasive urinary tract infection throughout its within-patient development and cross-patient transmission. Mouse peritoneal infection models and plasmid transformation experiments confirmed that the redundancy of frmA, an alcohol dehydrogenase gene, is linked to both enhanced virulence and increased biofilm mass in Acinetobacter baumannii. Additional analysis of 898 Enterobacter cloacae complex genomes revealed that redundant metal ion resistance genes carried by mobile genetic elements may provide selective advantages. This study unveiled a moderate gene redundancy within prokaryotes, providing genetic insights into the adaptive evolution and clinical infection of pathogens.