Pseudogenes act as a neutral reference for detecting selection in prokaryotic pangenomes

Area of Science:

• Microbial genomics
• Evolutionary biology
• Bacterial genetics

Background:

• Bacterial pangenomes comprise accessory genes, but forces driving their divergence (genetic drift vs. selection) are debated.
• Rare genes, including singletons, constitute a significant portion of pangenomes, with unclear adaptive, deleterious, or neutral roles.
• Previous models linking effective population size (Ne) to pangenome size have been interpreted through both neutral and adaptive lenses.

Purpose of the Study:

• To differentiate between neutral and adaptive models of bacterial pangenome evolution.
• To investigate the evolutionary forces shaping rare accessory gene content in bacteria.
• To establish a method for inferring the fitness effects of rare genes using pseudogenes as a neutral reference.

Main Methods:

• Utilized pseudogenes as a neutral evolutionary marker to assess the roles of rare genes.
• Analyzed gene family pseudogene and intact gene copy numbers across bacterial genomes.
• Defined and calculated the ratio of singleton intact genes to singleton pseudogenes (si/sp) across 668 prokaryotic species.

Main Results:

• Most functional categories showed depletion of rare pseudogenes when only one intact copy of a gene family was present.
• Transposable elements were enriched in pseudogenes, suggesting neutral or deleterious roles.
• The singleton intact to singleton pseudogene ratio (si/sp) indicated adaptive value for many rare accessory genes across diverse prokaryotes.

Conclusions:

• Pseudogene analysis provides a robust method to infer evolutionary forces in bacterial pangenomes.
• Rare accessory genes are not solely neutral or deleterious; many confer adaptive advantages.
• This study refines our understanding of bacterial genome evolution and the significance of accessory gene content.