Chromosomal origin of replication coordinates logically distinct types of bacterial genetic regulation

Abstract

For a long time it has been hypothesized that bacterial gene regulation involves an intricate interplay of the transcriptional regulatory network (TRN) and the spatial organization of genes in the chromosome. Here we explore this hypothesis both on a structural and on a functional level. On the structural level, we study the TRN as a spatially embedded network. On the functional level, we analyze gene expression patterns from a network perspective ("digital control"), as well as from the perspective of the spatial organization of the chromosome ("analog control"). Our structural analysis reveals the outstanding relevance of the symmetry axis defined by the origin (Ori) and terminus (Ter) of replication for the network embedding and, thus, suggests the coevolution of two regulatory infrastructures, namely the transcriptional regulatory network and the spatial arrangement of genes on the chromosome, to optimize the cross-talk between two fundamental biological processes: genomic expression and replication. This observation is confirmed by the functional analysis based on the differential gene expression patterns of more than 4000 pairs of microarray and RNA-Seq datasets for E. coli from the Colombos Database using complex network and machine learning methods. This large-scale analysis supports the notion that two logically distinct types of genetic control are cooperating to regulate gene expression in a complementary manner. Moreover, we find that the position of the gene relative to the Ori is a feature of very high predictive value for gene expression, indicating that the Ori-Ter symmetry axis coordinates the action of distinct genetic control mechanisms.

The nucleoid-associated protein IHF acts as a “domainin” protein coordinating the bacterial virulence traits with global transcription

“…On the other hand, the comparison of the wild-type and ihfA mutant cells shows a difference between the chromosomal arms which again, is augmented under conditions of DNA relaxation. This differential effect of IHF on chromosomal arms is fully consistent with the observed spatial organization of transcriptional regulatory networks along the replichores in E. coli [80,81]. Thus, the regulatory impacts of IHF and DNA supercoiling appear organized along the orthogonal axes (respectively along the OriC -Ter axis, and the lateral axis) of the chromosome.…”

The nucleoid-associated protein IHF acts as a ‘transcriptional domainin’ protein coordinating the bacterial virulence traits with global transcription

“…On the other hand, the comparison of the wild-type and ihfA mutant cells shows a conspicuous difference between the right and left chromosomal arms which again, is augmented under conditions of DNA relaxation. This differential regulatory effect on chromosomal arms is reminiscent of the observed spatial organization of transcriptional regulatory networks along the replichores in E. coli ( 84 , 85 ). Thus, the regulatory impacts of IHF and DNA supercoiling appear organized along the orthogonal axes (respectively along the OriC – Ter axis, and the lateral axis) of the chromosome.…”

The Location of Substitutions and Bacterial Genome Arrangements

“…To date there has been a large body of work looking at how molecular trends such as gene expression ( Couturier and Rocha 2006 ; Cooper et al. 2010 ; Morrow and Cooper 2012 ; Kosmidis et al. 2020 ; Lato and Golding 2020 ), substitution rates ( Sharp et al.…”

“…Prior research on molecular trends when moving from the origin of replication to the terminus have determined that gene expression is increased near the origin ( Couturier and Rocha 2006 ; Kosmidis et al. 2020 ; Lato and Golding 2020 ), and genes become less conserved with increasing distance from the origin ( Rocha and Danchin 2004 ; Couturier and Rocha 2006 ).…”

“…2010 ). The placement of these two gene categories may explain why near the origin, gene expression and essentiality are high ( Couturier and Rocha 2006 ; Kosmidis et al. 2020 ; Lato and Golding 2020 ) and substitution rate is low ( Flynn et al.…”