Abstract
In bacterial circular chromosomes and most plasmids, the replication is known to be terminated when either of the following occurs: the forks progressing in opposite directions meet at the distal end of the chromosome or the replication forks become trapped by Tus proteins bound to Ter sites. Most bacterial genomes have various polarities in their genomic structures. The most notable feature is polar genomic compositional asymmetry of the bases G and C in the leading and lagging strands, called GC skew. This asymmetry is caused by replication-associated mutation bias, and this “footprint" of the replication machinery suggests that, in contrast to the two known mechanisms, replication termination occurs near the chromosome dimer resolution site dif. To understand this difference between the known replication machinery and genomic compositional bias, we undertook a simulation study of genomic mutations, and we report here how different replication termination models contribute to the generation of replication-related genomic compositional asymmetry. Contrary to naive expectations, our results show that a single finite termination site at dif or at the GC skew shift point is not sufficient to reconstruct the genomic compositional bias as observed in published sequences. The results also show that the known replication mechanisms are sufficient to explain the position of the GC skew shift point.
Highlights
A circular bacterial chromosome has both a replication origin and a terminus, and replication of the chromosome proceeds bidirectionally from the origin to the terminus [1,2,3,4]
The collision of two opposing replication forks at a region approximately opposite the origin was initially suggested to be the predominant mechanism of termination in these organisms [6]; the finding that moving the replication origin does not change the replication terminus in E. coli [7,8] led to the identification of a fork-trapping mechanism involving the 36 kDa Tus protein in E. coli [9], and the 14.5 kDa RTP protein in B. subtilis, bound to Ter elements [10,11]
GC skew formation simulation Because GC skew represents the evolutionary footprint of a replication-related mutational bias, we attempted to elucidate the contributions of different replication termination models by computationally reconstructing the GC skew pattern using simulations of strand-biased mutations
Summary
A circular bacterial chromosome has both a replication origin and a terminus, and replication of the chromosome proceeds bidirectionally from the origin to the terminus [1,2,3,4]. Tus or RTP protein binds to the Ter sites (in E. coli, at the sequence 59AGNATGTTGTAAYKAA-39: [12]; in B. subtilis, at 59-KMACTAANWNNWCTATGTACYAAATNTTC- 39: [13]) and forms a barrier called a fork trap [14,15]. This fork trap acts as an antihelicase and allows forks to enter but not exit the terminus region [16,17]. In E. coli, most Ter sites are located in the terminus half of the genome [9,20]
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