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J Mol Evol. 2000 Mar;50(3):249-57.

The contributions of replication orientation, gene direction, and signal sequences to base-composition asymmetries in bacterial genomes.

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Department of Molecular and Medical Genetics, University of Toronto, 1 King's College Circle, Toronto, Canada M5S 1A8.


Asymmetries in base composition between the leading and the lagging strands have been observed previously in many prokaryotic genomes. Since a majority of genes is encoded on the leading strand in these genomes, previous analyses have not been able to determine the relative contribution to the base composition skews of replication processes and transcriptional and/or translational forces. Using qualitative graphical presentations and quantitative statistical analyses (analysis of variance), we have found that a significant proportion of the GC and AT skews can be attributed to replication orientation, i.e., the sequence of a gene is influenced by whether it is encoded on the leading or lagging strand. This effect of replication orientation on skews is independent of, and can be opposite in sign to, the effects of transcriptional or translational processes, such as selection for codon usage, amino acid preferences, expression levels (inferred from codon adaptation index), or potential short signal sequences (e.g., chi sequences). Mutational differences between the leading and the lagging strands are the most likely explanation for a significant proportion of the base composition skew in these bacterial genomes. The finding that base composition skews due to replication orientation are independent of those due to selection for function of the encoded protein may complicate the interpretation of phylogenetic relationships, conserved positions in nucleotide or amino acid sequence alignments, and codon usage patterns.

[Indexed for MEDLINE]

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