Detection of fundamental principles and a level of order for large-scale gene clustering on the Escherichia coli chromosome

Abstract

The Escherichia coli K-12 genetic map was divided into intervals of equal length to count the number of genes per interval. Plots of genes per interval at four sets of interval lengths revealed large-scale clustering of genes with the major clusters occurring at regularly spaced distances apart. Major gene cluster properties were analyzed at a scale of 100 intervals wherein each interval corresponded to a genetic map unit length of 1 min. In any major gene cluster, the highest gene concentration was observed at or near the midpoint interval, and the number of genes per interval was found to decline exponentially as a function of the linear distance from the midpoint or interval of peak gene concentration of that cluster. An autocorrelation analysis of gene content in first-neighbor intervals throughout the chromosome revealed an ordered first-neighbor relationship in comparison to 2,000 randomized interval versions of the chromosome. Attempts to simulate gene placement by a Gaussian model did not produce large-scale gene clustering in any way comparable to that observed on the chromosome. We propose that major gene clusters formed from smaller gene clusters, and the contemporary chromosome formed from fusion of homologous or heterologous major gene clusters.

A Theoretical Limit to Coding Space in Chromosomes of Bacteria

“…In that study (Williamson et al, 1993), the theoretical maximum coding space would contain 4,181 nonoverlapping genes of 1,100-bp average length in a 4.6-mb chromosome. By the preced-JACKSON ET AL.…”

“…An analysis of the patterns of gene arrangement on the 1990 genetic map of Escherichia coli revealed the presence of scale-independent gene clustering (Williamson et al, 1993). A mathematical model derived from the clustering pattern at a scale of 1-centisome intervals (Eq.…”

“…Each interval, i, on the bacterial chromosome falls within a major gene cluster and contains a gene concentration, C i , at a major cluster interval S i . The decrease in gene content per interval as a function of distance from the peak interval, DS i 5 u S i 2 S p u , is described by dC/dS 5 2bC, from which Equation 1 is derived by successive integration, and b is a measured constant (Williamson et al, 1993). Since the content of genes, C i , in each interval of a major cluster is proportionate to the gene content C p in the peak interval, the maximum value for M j occurs when C p reaches a maximum, that is, when all space in the S p interval is coding space.…”

“…The implication is that noncoding space exists within major clusters, even when the peak interval is packed with contiguous genes, as long as the pattern is conserved. An assumption of pattern conservation is a reasonable expectation owing to the consistency of the pattern for 14 major clusters using a large sample size of known genes (Williamson et al, 1993). Then, let y i represent any noncoding interval of any major cluster, M j .…”

“…A mathematical model derived from the clustering pattern at a scale of 1-centisome intervals (Eq. 1) was used to compute a theoretical maximum number of functional genes in the E. coli chromosome (Williamson et al, 1993). (1) This model (Equation 1) represents n 5 14 major clusters of M j genes each, with an interval S p of peak gene content C p in each major cluster.…”