Abstract
BackgroundDue to their bi-directional replication machinery starting from a single finite origin, bacterial genomes show characteristic nucleotide compositional bias between the two replichores, which can be visualised through GC skew or (C-G)/(C+G). Although this polarisation is used for computational prediction of replication origins in many bacterial genomes, the degree of GC skew visibility varies widely among different species, necessitating a quantitative measurement of GC skew strength in order to provide confidence measures for GC skew-based predictions of replication origins.ResultsHere we discuss a quantitative index for the measurement of GC skew strength, named the generalised GC skew index (gGCSI), which is applicable to genomes of any length, including bacterial chromosomes and plasmids. We demonstrate that gGCSI is independent of the window size and can thus be used to compare genomes with different sizes, such as bacterial chromosomes and plasmids. It can suggest the existence of different replication mechanisms in archaea and of rolling-circle replication in plasmids. Correlation of gGCSI values between plasmids and their corresponding host chromosomes suggests that within the same strain, these replicons have reproduced using the same replication machinery and thus exhibit similar strengths of replication strand skew.ConclusionsgGCSI can be applied to genomes of any length and thus allows comparative study of replication-related mutation and selection pressures in genomes of different lengths such as bacterial chromosomes and plasmids. Using gGCSI, we showed that replication-related mutation or selection pressure is similar for replicons with similar machinery.
Highlights
Due to their bi-directional replication machinery starting from a single finite origin, bacterial genomes show characteristic nucleotide compositional bias between the two replichores, which can be visualised through GC skew or (C-G)/(C+G)
In order to allow comparative study of the degree of GC skew in bacterial genomes, we have previously reported the GC skew index (GCSI), which quantifies the strength of GC skew in given bacterial chromosomes and can be used as a confidence measure for GC skew-based predictions or for the comparative study of replicationrelated mutation or selection pressures in bacterial chromosomes [20]
Principle and Design of generalised GC skew index (gGCSI) The original GCSI required the use of 4096 windows for optimal computation in bacterial genomes, but this fixed number of windows made GCSI only applicable to genomes larger than approximately 400 kbp; each window contained at least 100 bp
Summary
Due to their bi-directional replication machinery starting from a single finite origin, bacterial genomes show characteristic nucleotide compositional bias between the two replichores, which can be visualised through GC skew or (C-G)/(C+G). Analysis of the GC skew of a bacterial chromosome is useful for the prediction of its replication origin and terminus [11] and, subsequently, its leading and lagging strands. The polarisation of nucleotide composition is suggested to affect the replication-directed architecture of genomes This includes the aforementioned replication-oriented sequence elements and gene orientation [13]; the degree of strand-specific mutational bias observed with GC skew analysis can be used as a reference for mutation or selection pressures that a genome receives due to the replication machinery [12,13,14,15]
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