Publication Date:
2012-09-25
Description:
Two key cellular processes, namely transcription and replication, require the opening of the DNA double helix and act differently on the two DNA strands, generating different mutational patterns (mutational asymmetry) that may result, after long evolutionary time, in different nucleotide compositions on the two DNA strands (compositional asymmetry). We elaborate on the simplest model of neutral substitution rates that takes into account the strand asymmetries generated by the transcription and replication processes. Using perturbation theory, we then solve the time evolution of the DNA composition under strand-asymmetric substitution rates. In our minimal model, the compositional and substitutional asymmetries are predicted to decompose into a transcription- and a replication-associated components. The transcription-associated asymmetry increases in magnitude with transcription rate and changes sign with gene orientation while the replication-associated asymmetry is proportional to the replication fork polarity. These results are confirmed experimentally in the human genome, using substitution rates obtained by aligning the human and chimpanzee genomes using macaca and orangutan as outgroups, and replication fork polarity determined in the HeLa cell line as estimated from the derivative of the mean replication timing. When further investigating the dynamics of compositional skew evolution, we show that it is not at equilibrium yet and that its evolution is an extremely slow process with characteristic time scales of several hundred Myrs. Graphical abstract Content Type Journal Article Category Regular Article Pages 1-25 DOI 10.1140/epje/i2012-12092-y Authors A. Baker, Université de Lyon, F-69000 Lyon, France H. Julienne, Université de Lyon, F-69000 Lyon, France C. L. Chen, Centre de Génétique Moléculaire, CNRS, Allée de la Terrasse, 91198 Gif-sur-Yvette, France B. Audit, Université de Lyon, F-69000 Lyon, France Y. d’Aubenton-Carafa, Centre de Génétique Moléculaire, CNRS, Allée de la Terrasse, 91198 Gif-sur-Yvette, France C. Thermes, Centre de Génétique Moléculaire, CNRS, Allée de la Terrasse, 91198 Gif-sur-Yvette, France A. Arneodo, Université de Lyon, F-69000 Lyon, France Journal The European Physical Journal E: Soft Matter and Biological Physics Online ISSN 1292-895X Print ISSN 1292-8941 Journal Volume Volume 35 Journal Issue Volume 35, Number 9
Print ISSN:
1292-8941
Electronic ISSN:
1292-895X
Topics:
Physics
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