Visualizing Chromosomes, Cell Cycles, and Entropy

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David Goodsell is a legendary figure whose scientific illustrations have inspired many. When I first entered the bacterial chromosome field in 2004 as a theoretical physicist, his illustration was a definite guide to the inner space of Escherichia coli. It conveyed the right sense of scale and the numbers of different types of proteins and biomolecules inside the cell. Goodsell regularly updates his illustrations to incorporate up-to-date information from the scientific literature. A detailed explanation behind his work process can be found in Miniseries: Illustrating the Machinery of Life, Escherichia coli (Biochem Mol Biol Educ. 2009 [37]: 325-332).

In recent years, my lab has been taking multidisciplinary approaches to understand the physical principles that drive organization and segregation of the chromosomes in bacteria. For example, we have revealed the fundamentally “soft” nature of the bacterial chromosome and the entropic forces that can compact it in a crowded intracellular environment (Pelletier et al. Physical manipulation of the Escherichia coli chromosome reveals its soft nature. PNAS Plus. 2012; 109 [40]: E2649–2656), which motivated the work by Shendruk et al. in this issue of Biophysical Journal (108 [4]: February 17, 2015).

In the meantime, Stuart Austin’s group at the National Cancer Institute was tackling what had been considered impossible. They started the measurements and analysis of intracellular positions of dozens of dual genomic loci markers under overlapping cell-cycle conditions. This is a daunting task because, for any given moment, every cell contains several homologous copies of each genomic locus, and deciphering the organization and dynamics of the whole chromosome based on their positional information was something that had never been done before. Nevertheless, Stuart’s group relentlessly pushed their efforts without publishing anything for several years. When the task was done, the end result was simple, elegant, and surprising. The organization of the chromosome during multifork replication was that of a simple branched donut, with the two arms of the chromosome occupying each cell half along the radial axis of the cell. This result could not have been predicted based on our knowledge of the slowest-growing cells, but it encompasses all the previously known results and moves beyond them into something new and general (Youngren et al. The multifork Escherichia coli chromosome is a self-duplicating and self-segregating thermodynamic ring polymer. Genes Dev. 2014 [28]: 71-84).

Because of these radical new findings, I felt that David Goodsell’s famous illustration of E. coli would benefit from revision. Our cover image is the result of 12 revisions. A high-resolution file of Goodsell’s E. coli illustration can be downloaded from my lab web site: http://jun.ucsd.edu.

–Suckjoon Jun

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