Analyzing genomes with cumulative skew diagrams

Abstract

A novel method of cumulative diagrams shows that the nucleotide composition of a microbial chromosome changes at two points separated by about a half of its length. These points coincide with sites of replication origin and terminus for all bacteria where such sites are known. The leading strand is found to contain more guanine than cytosine residues. This fact is used to predict origin and terminus locations in other bacterial and archaeal genomes. Local changes, visible as diagram distortions, may represent recent genome rearrangements, as demonstrated for two strains of Escherichia coli. Analysis of the diagrams of viral and mitochondrial genomes suggests a link between the base composition bias and the time spent by DNA in a single stranded state during replication.

Nucleotide Composition of the Genomic and Protein-Coding Sequences in the two DNA Strands

“…The deviation between guanine and cytosine was greater than that between adenine and thymine in three species. This result reconfirmed that the asymmetry of GC is greater than that of AT [9]. The deviation between guanine and cytosine and that between adenine and thymine in leading strand was close to the corresponding one in lagging strand with opposite sign.…”

“…It is considered that the biased mutational occurrences due to the different replication mechanism between leading and lagging strands might be the cause of compositional asymmetry. Plots of cumulative GC skew of E. coli genomic sequence indicated maximum and minimum points [9]. The minimum point is consistent with the site of replication origin and the maximum with terminus, and the nucleotide composition asymmetry reversed at these two points in the genomic sequence.…”

“…However, the AT/GC skew profiles of mtDNAs of human and fruit fly gave no maximum nor minimum. In E. coli and B. subtilis, the minimum and maximum points were in correspondence with the experimentally determined origin and terminus of DNA replication [9]. In M. jannaschii, the sites of origin and terminus are not experimentally determined.…”

“…The GC skew profile of E. coli genomic sequence is shown in Fig.1. The maximum and minimum sites are located at 1.58 Mbp and 3.92 Mbp, they correspond to the terminus and origin of DNA replication [9]. Similarly, GC skew profiles of B. subtilis and M. jannaschii were obtained using their genomic sequences.…”

“…The compositional asymmetry in a genomic sequence has been reported [7][8][9][10]. It is considered that the biased mutational occurrences due to the different replication mechanism between leading and lagging strands might be the cause of compositional asymmetry.…”