Measures of compositional strand bias related to replication machinery and its applications

Abstract

The compositional asymmetry of complementary bases in nucleotide sequences implies the existence of a mutational or selectional bias in the two strands of the DNA duplex, which is commonly shaped by strand-specific mechanisms in transcription or replication. Such strand bias in genomes, frequently visualized by GC skew graphs, is used for the computational prediction of transcription start sites and replication origins, as well as for comparative evolutionary genomics studies. The use of measures of compositional strand bias in order to quantify the degree of strand asymmetry is crucial, as it is the basis for determining the applicability of compositional analysis and comparing the strength of the mutational bias in different biological machineries in various species. Here, we review the measures of strand bias that have been proposed to date, including the ∆GC skew, the B(1) index, the predictability score of linear discriminant analysis for gene orientation, the signal-to-noise ratio of the oligonucleotide bias, and the GC skew index. These measures have been predominantly designed for and applied to the analysis of replication-related mutational processes in prokaryotes, but we also give research examples in eukaryotes.

Keywords: GC skew; Nucleotide composition bias; bacterial replication; replication-related mutations..

Fig. (1)

Distribution of the S/N of oligomer skew in different phyla of eubacteria. The degree of replication-associated strand bias shows a characteristic distribution among the bacterial phyla, and Firmicutes is one of the most highly biased groups. The majority of the Firmicutes contain the polC subunit of the DNA polymerase, which results in a high gene strand bias. In comparison, proteobacteria belong to a group with a moderate degree of strand bias.

Fig. (2)

Clustering of the measures of strand bias and growth rate by Pearson correlations in 1083 bacterial genomes (only 254 genomes were used for 1/generation time). All strand bias measures are highly correlated (most above r > 0.70) and are also weakly correlated with properties related to the growth rate (r > 0.25).

Fig. (3)

Examples of GC skew graphs using the G-language GAE web service. G-language REST web service can be easily used by typing a URL in a browser starting with http://rest.g-language.org/ followed by a set of commands. Here, the GC skew graphs of Escherichia coli (NC_000913) are visualized using different sets of options, such as normal or wider windows (window=100000), a cumulative graph (cumulative=1), and the AT skew at a window size of 10000 bp (at=1, window=10000). Neither registration nor setup is required to use these services, allowing the user to readily make use of these tools for their research.