MBE Advance Access published online on July 23, 2007
Molecular Biology and Evolution, doi:10.1093/molbev/msm148
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Research Article |
A New Method for Assessing the Effect of Replication on DNA Base Composition Asymmetry
ulea1Affiliation for all authors: Université de Lyon ; université Lyon 1 ; CNRS ; UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, 43 boulevard du 11 novembre 1918, Villeurbanne F-69622, France; HELIX, Unité de recherche INRIA
1 Corresponding author: Tel: +33472433582; Fax: +33472431388; Email: necsulea{at}biomserv.univ-lyon1.fr; Address: Laboratoire de Biométrie et Biologie Évolutive (UMR 5558); CNRS; Univ. Lyon 1, 43 bd 11 nov, 69622, Villeurbanne Cedex, France
Received for publication March 27, 2007. Revision received June 14, 2007. Accepted for publication July 3, 2007.
DNA base composition asymmetry is at the basis of numerous in-silico methods for the detection of the origin and terminus of replication in prokaryotes. However, most of these methods are unable to identify the evolutionary mechanisms that cause the base composition asymmetry.
In prokaryotic chromosomes, due to the tendency for co-orientation between replication and transcription, compositional biases that discriminate the leading strand from the lagging strand can be produced by two superposing mechanisms: replication-associated mutation bias and coding sequence-associated bias (such as transcription-related mutational processes or selective pressures on codon usage).
We propose here a new method for the analysis of nucleotide composition asymmetry, that allows the decoupling of replication-related and coding sequence-related mechanisms. This method is inspired by a recent work (Nikolaou and Almirantis, 2005), that proposed an artificial chromosomal rearrangement meant to create a perfect gene orientation bias. We show that the study of nucleotide skews on the artificially rearranged chromosomes is a powerful means to assess the contributions of the two types of mechanisms in generating the base composition asymmetry. We applied our method to all completely sequenced prokaryotic chromosomes available. Our results confirm that in most species the replication mechanism has an important effect on base composition asymmetry, but also that it has different impacts on GC and AT-skews.
We also analyzed the variability in AT-skew direction encountered in prokaryotes. In disagreement with a recent report (Worning et al., 2006), we find that the polymerase-
subunits encoded in a genome are not sufficient to predict the sign of the AT-skew on its leading strand for replication.
Key Words: DNA base composition asymmetry • origin of replication • replication-induced mutation bias • transcription orientation • bacterial genomes
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