Quantitative analysis of replication-related mutation and selection pressures in bacterial chromosomes and plasmids using generalised GC skew index

Abstract

Background: 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). 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.

Results: Here 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.

Conclusions: gGCSI 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.

Figure 1

Correlation of old and new GC skew index (GCSI) values. Plot of GCSI (X-axis) and gGCSI (Y-axis) values for 822 bacterial chromosomes with 4096 windows.

Figure 2

Difference in GC skew strength between eubacteria and archaea. Plot of gGCSI (X-axis) and z-score (Y-axis) for chromosomes of 710 eubacteria (black crosses) and 53 archaea (red closed circles) with 512 windows. Most of the archaeal chromosomes are located in the lower left corner, where gGCSI < 0.1 and z-score < 5.

Figure 3

Difference in GC skew strength between RCR and non-RCR plasmids. Plot of gGCSI (X-axis) and z-score (Y-axis) for 211 RCR (red circles) and 697 non-RCR (black crosses) plasmids with 64 windows. Most RCR plasmids have gGCSI > 0.1 and z-score < 2, whereas non-RCR replicons show correlation in z-score and gGCSI.

Figure 4

Correlation of GC skew strength between plasmids and hosts. Log-log plot of gGCSI of plasmids against that of their corresponding host chromosomes.