Bacterial chromosomal gene positioning is likely shaped by selection on both mean and growth-dependent expression
- 1Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, Michigan, United States of America
Abstract
In bacteria with circular chromosomes, genes near the replication origin (oriC) are replicated earlier and consequently attain higher copy numbers than genes near the terminus (ter), particularly during rapid growth. Hence, mutations altering a gene’s chromosomal position can affect its expression level and be subject to selection. Two non–mutually exclusive hypotheses regarding the target of this selection have been proposed. The mean expression hypothesis (MEH) posits that the target is a gene’s average expression across environments, whereas the growth-dependent expression hypothesis (GEH) proposes that the target is the growth dependence of gene expression, quantified by the expression slope—the change in expression level per unit change in growth rate. To test these hypotheses and assess their relative support, we analyze eight multi-environment protein expression datasets from three bacterial species, as well as Escherichia coli promoter strengths measured in two environments. Consistent with both MEH and GEH, we observe a significant decrease in both mean expression and expression slope from oriC to ter in six and four of the eight datasets, respectively. In regression models predicting gene position, the relative contributions of the two hypotheses differ across species. However, even when combined, the two hypotheses explain only a small fraction of chromosomal gene positioning, in part because the replication-dose effect is incompletely offset by compensatory evolution of individual promoter strengths. The positional gradients in mean and growth-dependent expression are disproportionately contributed by genes involved in translation and transcription. We conclude that patterns of bacterial chromosomal gene positioning are consistent with moderate effects of selection on both mean and growth-dependent expression. Author summary: Bacterial gene positioning affects gene expression because genes near the origin of chromosomal replication are replicated earlier than those near the terminus and thus have higher gene copy numbers, especially during rapid population growth. Consequently, mutations altering the chromosomal position of a gene influence its expression so could be targeted by natural selection. Two hypotheses propose that the selection target is the mean expression level of a gene across environments and the growth dependence of expression, respectively. This study analyzed multi-environment protein expression datasets from three bacterial species to assess the two hypotheses. We found evidence for both hypotheses, but also discovered that, even when combined, the two hypotheses explain only a small fraction of chromosomal gene positioning, in part because the replication-dose effect is incompletely offset by compensatory evolution of individual promoter strengths. We conclude that patterns of bacterial chromosomal gene positioning are consistent with moderate effects of selection on both mean and growth-dependent expression, but more bacteria should be studied in the future to test the generality of our findings.
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BibTeX
@article{yuan2026bacterial,
title = {{Bacterial chromosomal gene positioning is likely shaped by selection on both mean and growth-dependent expression}},
author = {Ruiqi Yuan and Jianzhi Zhang},
journal = {PLOS Genetics},
year = {2026},
month = sep,
doi = {10.1371/journal.pgen.1012316},
url = {https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1012316},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Bacterial chromosomal gene positioning is likely shaped by selection on both mean and growth-dependent expression
AU - Ruiqi Yuan
AU - Jianzhi Zhang
PY - 2026
DA - 2026/09/21
JO - PLOS Genetics
DO - 10.1371/journal.pgen.1012316
UR - https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1012316
AB - In bacteria with circular chromosomes, genes near the replication origin (oriC) are replicated earlier and consequently attain higher copy numbers than genes near the terminus (ter), particularly during rapid growth. Hence, mutations altering a gene’s chromosomal position can affect its expression level and be subject to selection. Two non–mutually exclusive hypotheses regarding the target of this selection have been proposed. The mean expression hypothesis (MEH) posits that the target is a gene’s average expression across environments, whereas the growth-dependent expression hypothesis (GEH) proposes that the target is the growth dependence of gene expression, quantified by the expression slope—the change in expression level per unit change in growth rate. To test these hypotheses and assess their relative support, we analyze eight multi-environment protein expression datasets from three bacterial species, as well as Escherichia coli promoter strengths measured in two environments. Consistent with both MEH and GEH, we observe a significant decrease in both mean expression and expression slope from oriC to ter in six and four of the eight datasets, respectively. In regression models predicting gene position, the relative contributions of the two hypotheses differ across species. However, even when combined, the two hypotheses explain only a small fraction of chromosomal gene positioning, in part because the replication-dose effect is incompletely offset by compensatory evolution of individual promoter strengths. The positional gradients in mean and growth-dependent expression are disproportionately contributed by genes involved in translation and transcription. We conclude that patterns of bacterial chromosomal gene positioning are consistent with moderate effects of selection on both mean and growth-dependent expression. Author summary: Bacterial gene positioning affects gene expression because genes near the origin of chromosomal replication are replicated earlier than those near the terminus and thus have higher gene copy numbers, especially during rapid population growth. Consequently, mutations altering the chromosomal position of a gene influence its expression so could be targeted by natural selection. Two hypotheses propose that the selection target is the mean expression level of a gene across environments and the growth dependence of expression, respectively. This study analyzed multi-environment protein expression datasets from three bacterial species to assess the two hypotheses. We found evidence for both hypotheses, but also discovered that, even when combined, the two hypotheses explain only a small fraction of chromosomal gene positioning, in part because the replication-dose effect is incompletely offset by compensatory evolution of individual promoter strengths. We conclude that patterns of bacterial chromosomal gene positioning are consistent with moderate effects of selection on both mean and growth-dependent expression, but more bacteria should be studied in the future to test the generality of our findings.
SN - 1553-7404
ER -