Entropy as the driver of chromosome segregation

Abstract

We present a new physical biology approach to understanding the relationship between the organization and segregation of bacterial chromosomes. We posit that replicated Escherichia coli daughter strands will spontaneously demix as a result of entropic forces, despite their strong confinement within the cell; in other words, we propose that entropy can act as a primordial physical force which drives chromosome segregation under the right physical conditions. Furthermore, proteins implicated in the regulation of chromosome structure and segregation may in fact function primarily in supporting such an entropy-driven segregation mechanism by regulating the physical state of chromosomes. We conclude that bacterial chromosome segregation is best understood in terms of spontaneous demixing of daughter strands. Our concept may also have important implications for chromosome segregation in eukaryotes, in which spindle-dependent chromosome movement follows an extended period of sister chromatid demixing and compaction.

Physical manipulation of the Escherichia coli chromosome reveals its soft nature

“…The equilibrium volume of the in vitro chromosomes isolated in microchannels is several times smaller than the ones isolated in the absence of confinement (Table 1 and SI Appendix, Section II.B). This shape-dependent decrease in total chromosomal volume is consistent with a polymer model of the bacterial chromosome (11,17,44).…”

“…1 and 4), means that entropic forces can readily and dynamically influence the chromosome, from segregation and organization (11,13,17,44) to compaction (3,23), as suggested previously and demonstrated in this work.…”

“…The measured force-compression curves are consistent with an entropic spring model (11,17,25). The quantitative agreement between the data and the model allows us to estimate the force and free energy required to compress the in vitro chromosome to its in vivo size.…”

Independent Segregation of the Two Arms of theEscherichia coli oriRegion Requires neither RNA Synthesis nor MreB Dynamics

“…Blocking of replication in one replichore does not prevent segregation of loci on the other. It seems plausible that spontaneous chromosome segregation by entropic disentanglement of the chromosomal polymer (1,27,28) may provide the essence of the segregation mechanism. Therefore, the key to efficient and faithful segregation is likely to reside in chromosome organization itself and the processes that drive this organization, as well as independent replication by spatially separated replisomes tracking along the DNA and the subsequent decatenation by TopoIV.…”

“…Finally, thermodynamic considerations of the properties of a highly confined, self-avoiding polymer (representing a DNA molecule) in a rod-shaped cell-like geometry (representing a bacterial cell) have indicated that duplicated circular chromosomes could segregate spontaneously without any additional force in physiologically relevant timescales (1,27,28). Therefore, entropy alone may be sufficient to produce the observed segregation of replicated chromosomes, while plasmids use active partition systems because their small size in a "sea" of chromosomal DNA would not lead to effective spontaneous segregation.…”