Orphan Genes Shared by Pathogenic Genomes Are More Associated with Bacterial Pathogenicity

Area of Science:

• Genomics
• Microbiology
• Evolutionary Biology

Background:

• Orphan genes (ORFans) are unique or rarely found genes enabling organism adaptation.
• Comparative genomics reveals ORFans' role in bacterial evolution and pathogenicity.
• Understanding ORFans in pathogens versus nonpathogens is crucial for infectious disease research.

Purpose of the Study:

• To compare orphan genes (ORFans) between pathogenic and nonpathogenic bacteria within the same genus.
• To investigate the association between ORFans and pathogenicity-related genes (PRGs).
• To identify potential targets for novel antimicrobial strategies.

Main Methods:

• Pangenome analysis of 505 bacterial genomes across nine genera.
• Classification of ORFans into single-strain (SS) and pan-strain (PS) categories for both pathogens and nonpathogens.
• Correlation analysis of ORFan types with PRGs (prophages, PAIs, VFs, HGTs).

Main Results:

• Pathogens did not consistently possess more genes, ORFans, or PRGs than nonpathogens.
• Pathogenic bacteria showed a higher proportion of pan-strain ORFans (PS-ORFans) compared to single-strain ORFans (SS-ORFans).
• PS-ORFans in pathogens were more frequently associated with PRGs than SS-ORFans, unlike in nonpathogens.

Conclusions:

• Pan-strain orphan genes (PS-ORFans) are significantly associated with bacterial pathogenicity.
• Shared ORFans in pathogens represent promising targets for developing new diagnostic markers and therapeutic drugs.
• Comparative analysis of ORFans provides insights into bacterial adaptation and virulence mechanisms.