Nearly half of all bacterial gene families are biased toward specific chromosomal positions

Abstract

Many bacterial genes encoding components of the translation and transcription machinery occupy genomic positions close to the origin of genome replication. These positional biases are thought to result from selection for high expression levels, as genes close to the origin are the first to be duplicated after the initiation of DNA replication. However, recent work indicates that positional biases of RNA genes involved in translation have evolved to support optimal growth rate dependence of expression levels rather than high expression per se. We hypothesized that, more generally, natural selection may have favored the location of different genes at specific chromosomal positions to optimize the growth rate dependence of their relative gene copy numbers. Here we show that 49% of bacterial gene families are preferentially localized to specific chromosomal regions, with most families biased toward either the origin or the terminus of replication. From our hypothesis, we derive six specific predictions regarding the genes chromosomal positioning and functional categories, as well as the minimum cellular doubling times. All six predictions are robustly supported by comparative genomic analyses of 773 bacterial species and by proteomics data from Escherichia coli and Bacillus subtilis. Our findings reveal a complex relationship between bacterial growth, resource allocation and genome organization, and they provide new insights into the physiological significance and potential functions of a large number of gene families.