Data Sheet 2_Higher frequency of prokaryotic low complexity regions in core and orthologous genes.pdf

Prokaryotic genome evolution is shaped by mutation, gene duplication, and horizontal gene transfer, yet the interaction of these mechanisms, particularly in relation to low complexity regions (LCRs), remains poorly understood. LCRs are known to be mutation-prone and have been proposed to promote genetic innovation. However, the interaction between LCR-mediated and paralogy-mediated genetic innovation is still unclear. To clarify the interplay between these two evolutionary forces, we analyzed the distribution of LCRs in protein-coding genes from three closely related enterobacteria (Escherichia coli, Salmonella enterica, and Klebsiella pneumoniae) at both species and population levels. Using pangenomic and orthology-based approaches, we categorized genes by duplication history and conservation status and assessed LCR frequencies across these groups. We found that LCRs were consistently enriched in core and orthologous genes rather than in accessory or paralogous ones. This pattern was stable across evolutionary timescales and particularly pronounced in genes involved in cell cycle control and defense. These results suggest that, contrary to prior assumptions, LCRs may serve conserved functional roles rather than acting primarily as agents of evolutionary plasticity even at population-level timescales.