Most bacterial gene families are biased toward specific chromosomal positions.

The arrangement of genes along bacterial chromosomes influences their expression through growth rate–dependent gene copy number changes during DNA replication. Although translation- and transcription-related genes often cluster near the origin of replication, the extent of positional biases across gene families remains unclear. We hypothesized that natural selection broadly favors specific chromosomal positions to optimize growth rate–dependent expression. Analyzing 910 bacterial species and proteomics data from Escherichia coli and Bacillus subtilis, we found that about two-thirds of bacterial gene families are positionally biased. Natural selection drives genes mainly toward the origin or terminus of replication, with the strongest selection in fast-growing species. Our findings reveal chromosomal positioning as a fundamental mechanism for coordinating gene expression with growth rate, highlighting evolutionary constraints on bacterial genome architecture. Editor's summary: In bacteria's circular chromosomes, replication begins bidirectionally from one location (oriC) and ends at another (ter). Genes are still expressed during replication, so those near oriC are more likely to have multiple copies present and are more highly expressed during growth. Hu et al. analyzed chromosome positions for all genes across 910 bacterial species. Consistent with previous studies, they found that many transcription and translation genes were biased toward oriC. However, 65.8% of gene families showed bias toward particular positions, and these biases were stronger with higher growth rates. This work demonstrates that many more genes are positionally constrained in bacteria than was previously thought, possibly providing insight into the function of uncharacterized genes. —Corinne Simonti [ABSTRACT FROM AUTHOR]