4-D model of bacterial chromosome structure

摘要: Massive effort has been devoted to understanding biopolymer structure at the nanometer and micrometer scales. Very little success has been achieved studying their structure at intermediate scales. We outline a method to integrate data on the three dimensional structure of whole chromosomes and genomes. The method is based on evolutionary optimality. We hypothesize that the three dimensional structure of the chromosome is optimal for many of the functions that it performs. These functions determine geometrical and dynamical constraints that can be expressed mathematically. Our goal is to gather enough constraints to create a 4D model of the chromosome. Changes in the structure of the chromosome over time (the 4th dimension) will reflect the varying functional constraints on the genome during different phases of the cell cycle.We model the bacterium Mycoplasma pneumoniae. It is nearly a minimal cell with a genome that is 816 kbp long and only 688 genes. It has limited metabolism, no known regulation, and very few DNA binding proteins [1]. Since it is so simple, we expect chromosome structure to be under strong evolutionary selection. We use transcriptional efficiency to motivate two sets of constraints for our model. First, we expect most transmembrane genes to be close to the membrane [2] and second we anticipate that ribosome component genes can be spatially colocalized (as they are in nucleoli). Both sets of constraints reflect the efficiency of producing proteins near their targets. Additional constraints are provided by experimental observations of bacterial nucleoids and considerations of chromosome replication. Microscopy …