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A metabolic force for gene clustering

Authors: R.E. Svetic; K.L. Smythe; Julius H. Jackson; C.R MacCluer; C.O. Buckley;

A metabolic force for gene clustering

Abstract

Bacterial chromosomes frequently contain arrays of contiguous genes that group according to related metabolic roles. We propose that clustering of genes for metabolically related functions confers thermodynamic advantage to the organism based upon our protein immobility model (PIM) of intracellular diffusion. This thermodynamic effect provides the selection force argument that is missing from previous models of gene clustering. The PIM posits that clustered genes produce local clusters of enzymes in bacteria owing to the co-linearity of transcription and translation, and to the relative immobility of large proteins released into the cytosol. We maintain that the resulting physical proximity of enzymes for related pathway steps minimizes the steady state level of reaction step intermediates and thus conserves the energy and material required for rapid growth and maintenance. Support for this idea comes from in silico experiments using the PIM applied to a model metabolic pathway A --> B --> C. The metabolites A, B, and C are small molecules that diffuse freely in a cytosol crowded with macromolecules, whereas the large enzyme molecules, E1 and E2, tend to remain in the vicinity of their point of release. Modeling E1 as a source of B from A, and E2 as a sink for B, numerical experiments suggest that the steady state concentration of B in the cytosol increases approximately in proportion to the square of the distance of the E1 and E2 separation. A further model prediction is that the steady state concentration of B is influenced by the geometric effects of the spatial location and orientation of E1 relative to E2. These results suggest that: (i) gene clustering reduces the energy and material costs of enzyme reactions linked by metabolic intermediates; (ii) gene clusters near ori, the origin of replication, utilize the geometric effect to conserve free energy by further reducing the steady state concentration of the intermediate; (iii) gene organization on a chromosome influences the organism's capacity to accelerate into steady state growth and is, in turn, influenced by the abundance and frequency of access to nutrients.

Related Organizations
Keywords

Bacterial Proteins, Models, Genetic, Multigene Family, Thermodynamics, Gene Expression Regulation, Bacterial

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
15
Top 10%
Average
Average
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