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Borrelia burgdorferi, a causative agent of Lyme disease, contains the most segmented bacterial genome known to date, with one linear chromosome and over twenty plasmids. How this unusually complex genome is organized, and whether and how the different replicons interact are unclear. We recently demonstrated thatB.burgdorferiis polyploid and that the copies of the chromosome and plasmids are regularly spaced in each cell, which is critical for faithful segregation of the genome to daughter cells. Regular spacing of the chromosome is controlled by two separate partitioning systems that involve the protein pairs ParA/ParZ and ParB/Smc. Here, using chromosome conformation capture (Hi-C), we characterized the organization of theB.burgdorferigenome and the interactions between the replicons. We uncovered that although the linear chromosome lacks contacts between the two replication arms, the two telomeres are in frequent contact. Moreover, several plasmids specifically interact with the chromosomeoriCregion, and a subset of plasmids interact with each other more than with others. We found that Smc and the Smc-like MksB protein mediate long-range interactions on the chromosome, but they minimally affect plasmid-chromosome or plasmid-plasmid interactions. Finally, we found that disruption of the two partition systems leads to chromosome restructuring, correlating with the mis-positioning of chromosomeoriC. Altogether, this study revealed the conformation of a complex genome and analyzed the contribution of the partition systems and SMC family proteins to this organization. This work expands the understanding of the organization and maintenance of multipartite bacterial genomes. 

Exponentially growing systems are prevalent in nature, spanning all scales from biochemical reaction networks in single cells to food webs of ecosystems. How exponential growth emerges in nonlin- ear systems is mathematically unclear. Here, we describe a general theoretical framework that reveals underlying principles of long- term growth: scalability of flux functions and ergodicity of the rescaled systems. Our theory shows that nonlinear fluxes can gen- erate not only balanced growth but also oscillatory or chaotic growth modalities, explaining nonequilibrium dynamics observed in cell cycles and ecosystems. Our mathematical framework is broadly useful in predicting long-term growth rates from natural and synthetic networks, analyzing the effects of system noise and perturbations, validating empirical and phenomenological laws on growth rate, and studying autocatalysis and network evolution. 

Exponentially growing systems are prevalent in nature, spanning all scales from biochemical reaction networks in single cells to food webs of ecosystems. How exponential growth emerges in nonlin- ear systems is mathematically unclear. Here, we describe a general theoretical framework that reveals underlying principles of long- term growth: scalability of flux functions and ergodicity of the rescaled systems. Our theory shows that nonlinear fluxes can gen- erate not only balanced growth but also oscillatory or chaotic growth modalities, explaining nonequilibrium dynamics observed in cell cycles and ecosystems. Our mathematical framework is broadly useful in predicting long-term growth rates from natural and synthetic networks, analyzing the effects of system noise and perturbations, validating empirical and phenomenological laws on growth rate, and studying autocatalysis and network evolution.