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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.

SUBMITTER: Arakawa K

PROVIDER: S-EPMC3269016 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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

Arakawa Kazuharu K Tomita Masaru M

Current genomics 20120301 1

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 measure ...[more]

PMID: 22942671

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Project description:BACKGROUND: A GC-compositional strand bias or GC-skew (=(C-G)/(C+G)), where C and G denote the numbers of cytosine and guanine residues, was recently reported near the transcription start sites (TSS) of Arabidopsis genes. However, it is unclear whether other eukaryotic species have equally prominent GC-skews, and the biological meaning of this trait remains unknown. RESULTS: Our study confirmed a significant GC-skew (C > G) in the TSS of Oryza sativa (rice) genes. The full-length cDNAs and genomic sequences from Arabidopsis and rice were compared using statistical analyses. Despite marked differences in the G+C content around the TSS in the two plants, the degrees of bias were almost identical. Although slight GC-skew peaks, including opposite skews (C < G), were detected around the TSS of genes in human and Drosophila, they were qualitatively and quantitatively different from those identified in plants. However, plant-like GC-skew in regions upstream of the translation initiation sites (TIS) in some fungi was identified following analyses of the expressed sequence tags and/or genomic sequences from other species. On the basis of our dataset, we estimated that > 70 and 68% of Arabidopsis and rice genes, respectively, had a strong GC-skew (> 0.33) in a 100-bp window (that is, the number of C residues was more than double the number of G residues in a +/-100-bp window around the TSS). The mean GC-skew value in the TSS of highly-expressed genes in Arabidopsis was significantly greater than that of genes with low expression levels. Many of the GC-skew peaks were preferentially located near the TSS, so we examined the potential value of GC-skew as an index for TSS identification. Our results confirm that the GC-skew can be used to assist the TSS prediction in plant genomes. CONCLUSION: The GC-skew (C > G) around the TSS is strictly conserved between monocot and eudicot plants (ie. angiosperms in general), and a similar skew has been observed in some fungi. Highly-expressed Arabidopsis genes had overall a more marked GC-skew in the TSS compared to genes with low expression levels. We therefore propose that the GC-skew around the TSS in some plants and fungi is related to transcription. It might be caused by mutations during transcription initiation or the frequent use of transcription factor-biding sites having a strand preference. In addition, GC-skew is a good candidate index for TSS prediction in plant genomes, where there is a lack of correlation among CpG islands and genes.

Dataset Information

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

Publications

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

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