The GC skew index: a measure of genomic compositional asymmetry and the degree of replicational selection

Abstract

Circular bacterial chromosomes have highly polarized nucleotide composition in the two replichores, and this genomic strand asymmetry can be visualized using GC skew graphs. Here we propose and discuss the GC skew index (GCSI) for the quantification of genomic compositional skew, which combines a normalized measure of fast Fourier transform to capture the shape of the skew graph and Euclidean distance between the two vertices in a cumulative skew graph to represent the degree of skew. We calculated GCSI for all available bacterial genomes, and GCSI correlated well with the visibility of GC skew. This novel index is useful for estimating confidence levels for the prediction of replication origin and terminus by methods based on GC skew and for measuring the strength of replicational selection in a genome.

Keywords: DNA replication; GC skew; GCSI; bioinformatics; fast Fourier transforms; replicational selection.

Figure 1.

Scatter plot of spectral ratio RS against the Euclidean distance between the two vertices in cumulative graph dist. RS measures the goodness-of-fit of the “shape” of the overall GC skew to be partitioned into two segments corresponding the two replichores, by calculating the relative predominance of the spectral strength of the 1-Hz frequency component over other frequencies upon applying Fast Fourier Transform. dist measures the degree of bias in the leading and lagging strands, by calculating the Euclidean distance between the average GC skew in the two replichores. RS is generally correlated with dist, therefore combination of these two measures as GCSI should correctly represent both the shape of the graph and the degree of skew.

Figure 2.

GC skew graphs plotted with 500 windows for nine bacteria at different levels of GCSI. GC skew is not observable for the first two species at GCSI <0.05, and becomes evident at GCSI >0.08. At GCSI >0.1, graphs increase their skewness and the shift points and two replichores can be clearly discerned from the graph. Note that the range of Y-axis extends as GCSI values increase. Overall, GCSI correlates with and correctly captures the degree of skew.