The Role of Replication-induced Chromosomal Copy Numbers in Spatio-temporal Gene Regulation and Evolutionary Chromosome Plasticity

Abstract

For a coherent response to environmental changes, bacterial evolution has formed a complex transcriptional regulatory system comprising classical DNA binding proteins sigma factors and modulation of DNA topology. In this study, we investigate replication-induced gene copy numbers - a regulatory concept that is unlike the others not based on modulation of promoter activity but replication dynamics. We show that a large fraction of genes are predominantly affected by transient copy numbers and identify cellular functions and central pathways governed by this mechanism in Escherichia coli. Furthermore, we show quantitatively that the previously observed spatio-temporal expression pattern between different growth phases mainly emerges from transient chromosomal copy numbers. We extend the analysis to the plant pathogen Dickeya dadantii and the biotechnologically relevant organism Vibrio natriegens. The analysis reveals a connection between growth phase dependent gene expression and evolutionary gene migration in these species. Further extension to the bacterial kingdom shows that chromosome evolution is governed by growth rate related transient copy numbers.

Oligonucleotide Library Assisted Sequence Mining Reveals Promoter Sequences With Distinct Temporal Expression Dynamics For Applications InCurvibactersp. AEP1-3

“…This is in accordance with previous findings which show that bacterial cells are able to recall distinct global expression patterns based on their stage of growth by the spatio-temporal regulation of chromosomal macrodomains [32]. While replication induced transient changes in actual copy numbers are a factor directing genomic transcription biases along the oriC/ter axis [33], the regulation of macrodomains occurs for functionally similar genes through direct DNA topology and transcriptional control. While in trans expression systems are per definition not affected by positional effects of the promoter of interest (as they are taken out of their natural, genomic context), they are partially affected by DNA topology [34] (e.g.…”

Emergence and Inter- and Intrahost Evolution of Pandrug-Resistant Klebsiella pneumoniae Coharboring tmexCD1-toprJ1, bla NDM-1 , and bla KPC-2

“…It has been confirmed that the genes that are closer to the origin site ( ori proximal gene) are replicated first and are more highly expressed ( 26 , 27 ). In E. coli , higher expression of oriC-proximal genes has been discovered on the chromosome, which is caused by the replication-induced increase of copy numbers (up to eight copies) of the oriC proximal region ( 28 , 29 ). However, we did not find any evidence in previous studies about this phenomenon in the expression of genes in plasmids, which should be validated in the future.…”