Abstract
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.
Article PDF
Similar content being viewed by others
Explore related subjects
Discover the latest articles, news and stories from top researchers in related subjects.Avoid common mistakes on your manuscript.
References
R. Berezney, D.D. Dubey, J.A. Huberman, Chromosoma 108, 471 (2000)
D.M. Gilbert, Science 294, 96 (2001)
M. Méchali, Nat. Rev. Genet. 2, 640 (2001)
S.P. Bell, A. Dutta, Annu. Rev. Biochem. 71, 333 (2002)
A.J. McNairn, D.M. Gilbert, Bioessays 25, 647 (2003)
M.I. Aladjem, Nat. Rev. Genet. 8, 588 (2007)
S. Courbet, S. Gay, N. Arnoult, G. Wronka, M. Anglana, O. Brison, M. Debatisse, Nature 455, 557 (2008)
J.L. Hamlin, L.D. Mesner, O. Lar, R. Torres, S.V. Chodaparambil, L. Wang, J. Cell. Biochem. 105, 321 (2008)
M. Méchali, Nat. Rev. Mol. Cell Biol. 11, 728 (2010)
D.M. Gilbert, Nat. Rev. Genet. 11, 673 (2010)
J.R. Lobry, Mol. Biol. Evol. 13, 660 (1996)
J. Mrázek, S. Karlin, Proc. Natl. Acad. Sci. U.S.A. 95, 3720 (1998)
C.L. Chen, L. Duquenne, B. Audit, G. Guilbaud, A. Rappailles, A. Baker, M. Huvet, Y. d’Aubenton Carafa, O. Hyrien, A. Arneodo et al., Mol. Biol. Evol. 28, 2327 (2011)
B. Alberts, A. Jonhson, J. Lewis, M. Raff, K. Roberts, P. Walter, Molecular Biology of the Cell, 5th edition (Garland Publishing, New York, 2008)
M.L. DePamphilis (Editor), DNA Replication and Human Disease (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 2006)
B. Audit, S. Nicolay, M. Huvet, M. Touchon, Y. d’Aubenton-Carafa, C. Thermes, A. Arneodo, Phys. Rev. Lett. 99, 248102 (2007)
A. Baker, B. Audit, C. Chen, B. Moindrot, A. Leleu, G. Guilbaud, A. Rappailles, C. Vaillant, A. Goldar, F. Mongelard et al., PLoS Comput. Biol. 8, e1002443 (2012)
M. Touchon, S. Nicolay, B. Audit, E.B. Brodie of Brodie, Y. d’Aubenton-Carafa, A. Arneodo, C. Thermes, Proc. Natl. Acad. Sci. U.S.A. 102, 9836 (2005)
E.B. Brodie of Brodie, S. Nicolay, M. Touchon, B. Audit, Y. d’Aubenton-Carafa, C. Thermes, A. Arneodo, Phys. Rev. Lett. 94, 248103 (2005)
S. Nicolay, PhD Thesis, University of Liège, Belgium (2006)
M. Huvet, S. Nicolay, M. Touchon, B. Audit, Y. d’Aubenton-Carafa, A. Arneodo, C. Thermes, Genome Res. 17, 1278 (2007)
B. Audit, L. Zaghloul, C. Vaillant, G. Chevereau, Y. d’Aubenton Carafa, C. Thermes, A. Arneodo, Nucl. Acids Res. 37, 6064 (2009)
C. Lemaitre, L. Zaghloul, M.F. Sagot, C. Gautier, A. Arneodo, E. Tannier, B. Audit, BMC Genomics 10, 335 (2009)
L. Zaghloul, PhD Thesis, ENS de Lyon, France (2009)
R.S. Hansen, S. Thomas, R. Sandstrom, T.K. Canfield, R.E. Thurman, M. Weaver, M.O. Dorschner, S.M. Gartler, J.A. Stamatoyannopoulos, Proc. Natl. Acad. Sci. U.S.A. 107, 139 (2010)
M. Touchon, S. Nicolay, A. Arneodo, Y. d’Aubenton-Carafa, C. Thermes, FEBS Lett. 555, 579 (2003)
M. Touchon, A. Arneodo, Y. d’Aubenton-Carafa, C. Thermes, Nucl. Acids Res. 32, 4969 (2004)
C.L. Chen, A. Rappailles, L. Duquenne, M. Huvet, G. Guilbaud, L. Farinelli, B. Audit, Y. d’Aubenton-Carafa, A. Arneodo, O. Hyrien et al., Genome Res. 20, 447 (2010)
G. Guilbaud, A. Rappailles, A. Baker, C.L. Chen, A. Arneodo, A. Goldar, Y. d’Aubenton-Carafa, C. Thermes, B. Audit, O. Hyrien, PLoS Comput. Biol. 7, e1002322 (2011)
N. Sueoka, J. Mol. Evol. 40, 318 (1995)
R. Rudner, J.D. Karkas, E. Chargaff, Proc. Natl. Acad. Sci. U.S.A. 60, 921 (1968)
J.R. Lobry, J. Mol. Evol. 40, 326 (1995)
J.R. Lobry, C. Lobry, Mol. Biol. Evol. 16, 719 (1999)
A. Arneodo, C. Vaillant, B. Audit, F. Argoul, Y. d’Aubenton-Carafa, C. Thermes, Phys. Rep. 498, 45 (2011)
M.P. Francino, H. Ochman, Trends Genet 13, 240 (1997)
A.C. Frank, J.R. Lobry, Gene 238, 65 (1999)
M.P. Francino, H. Ochman, Mol. Biol. Evol. 18, 1147 (2001)
P. Green, B. Ewing, W. Miller, P.J. Thomas, E.D. Green, Nat. Genet. 33, 514 (2003)
P. Polak, P.F. Arndt, Genome Res. 18, 1216 (2008)
C.F. Mugal, H.H. von Grunberg, M. Peifer, Mol. Biol. Evol. 26, 131 (2009)
A. Beletskii, A.S. Bhagwat, Proc. Natl. Acad. Sci. U.S.A. 93, 13919 (1996)
A. Beletskii, A.S. Bhagwat, Biol. Chem. 379, 549 (1998)
M.P. Francino, L. Chao, M.A. Riley, H. Ochman, Science 272, 107 (1996)
J.Q. Svejstrup, Nat. Rev. Mol. Cell Biol. 3, 21 (2002)
S. Nicolay, F. Argoul, M. Touchon, Y. d’Aubenton-Carafa, C. Thermes, A. Arneodo, Phys. Rev. Lett. 93, 108101 (2004)
S. Nicolay, E.B. Brodie of Brodie, M. Touchon, B. Audit, Y. d’Aubenton-Carafa, C. Thermes, A. Arneodo, Phys. Rev. E 75, 032902 (2007)
E.P. Rocha, A. Danchin, A. Viari, Mol. Microbiol. 32, 11 (1999)
E.P.C. Rocha, M. Touchon, E.J. Feil, Genome Res. 16, 1537 (2006)
P. Polak, P.F. Arndt, Genome Biol. Evol. 1, 189 (2009)
T.A. Kunkel, P.M. Burgers, Trends Cell Biol. 18, 521 (2008)
J.R. Lobry, Science 272, 745 (1996)
E.R. Tillier, R.A. Collins, J. Mol. Evol. 50, 249 (2000)
A. Grigoriev, Virus Res. 60, 1 (1999)
A. Gierlik, M. Kowalczuk, P. Mackiewicz, M.R. Dudek, S. Cebrat, J. Theor. Biol. 202, 305 (2000)
A. Reyes, C. Gissi, G. Pesole, C. Saccone, Mol. Biol. Evol. 15, 957 (1998)
M.C. Marsolier-Kergoat, A. Goldar, Mol. Biol. Evol. 29, 893 (2012)
F. Jacob, S. Brenner, F. Cuzin, Cold Spring Harb. Symp. Quant. Biol. 28, 329 (1963)
D. Graur, W.H. Li, Fundamentals of Molecular Evolution (Sinauer Associates, Sunderland, MA, 1999)
M. Kimura, Nature 217, 624 (1968)
N. Galtier, G. Piganeau, D. Mouchiroud, L. Duret, Genetics 159, 907 (2001)
L. Duret, P.F. Arndt, PLoS Genet. 4, e1000071 (2008)
L. Duret, N. Galtier, Annu. Rev. Genomics Hum. Genet. 10, 285 (2009)
The ENCODE Project Consortium, Nature 447, 799 (2007)
J. Cheng, P. Kapranov, J. Drenkow, S. Dike, S. Brubaker, S. Patel, J. Long, D. Stern, H. Tammana, G. Helt et al., Science 308, 1149 (2005)
L.J. Core, J.J. Waterfall, J.T. Lis, Science 322, 1845 (2008)
Y. He, B. Vogelstein, V.E. Velculescu, N. Papadopoulos, K.W. Kinzler, Science 322, 1855 (2008)
P. Preker, J. Nielsen, S. Kammler, S. Lykke-Andersen, M.S. Christensen, C.K. Mapendano, M.H. Schierup, T.H. Jensen, Science 322, 1851 (2008)
A.C. Seila, J.M. Calabrese, S.S. Levine, G.W. Yeo, P.B. Rahl, R.A. Flynn, R.A. Young, P.A. Sharp, Science 322, 1849 (2008)
A. Necsulea, C. Guillet, J.C. Cadoret, M.N. Prioleau, L. Duret, Mol. Biol. Evol. 26, 729 (2009)
A. Baker, PhD Thesis, University of Lyon, France (2011)
L.A. Frederico, T.A. Kunkel, B.R. Shaw, Biochemistry 29, 2532 (1990)
J.A. Stamatoyannopoulos, I. Adzhubei, R.E. Thurman, G.V. Kryukov, S.M. Mirkin, S.R. Sunyaev, Nat. Genet. 41, 393 (2009)
C.F. Mugal, J.B.W. Wolf, H.H. von Grunberg, H. Ellegren, Genome Biol. Evol. 2, 19 (2010)
C.L. Chen, A. Baker, B. Audit, Y. d’Aubenton-Carafa, A. Arneodo, C. Thermes, in preparation (2012).
N. Van Kampen, Stochastic Processes in Physics and Chemistry, 3rd edition (North-Holland, Amsterdam, 2007)
T. Ryba, I. Hiratani, J. Lu, M. Itoh, M. Kulik, J. Zhang, T.C. Schulz, A.J. Robins, S. Dalton, D.M. Gilbert, Genome Res. 20, 761 (2010)
E. Yaffe, S. Farkash-Amar, A. Polten, Z. Yakhini, A. Tanay, I. Simon, PLoS Genet. 6, e1001011 (2010)
A. Baker, S. Nicolay, L. Zaghloul, Y. d’Aubenton-Carafa, C. Thermes, B. Audit, A. Arneodo, Appl. Comput. Harmon. Annal. 28, 150 (2010)
G. McVicker, P. Green, Genome Res. 20, 1503 (2010)
J. Majewski, Am. J. Hum. Genet. 73, 688 (2003)
J.M. Comeron, Genetics 167, 1293 (2004)
L. Duret, Curr. Opin. Genet. Dev. 12, 640 (2002)
D. Karolchik, R. Baertsch, M. Diekhans, T.S. Furey, A. Hinrichs, Y.T. Lu, K.M. Roskin, M. Schwartz, C.W. Sugnet, D.J. Thomas et al., Nucl. Acids Res. 31, 51 (2003)
M.M. Suzuki, A. Bird, Nat. Rev. Genet. 9, 465 (2008)
S.T. Hess, J.D. Blake, R.D. Blake, J. Mol. Biol. 236, 1022 (1994)
P.F. Arndt, T. Hwa, Bioinformatics 21, 2322 (2005)
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
Open Access This article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
About this article
Cite this article
Baker, A., Julienne, H., Chen, C.L. et al. Linking the DNA strand asymmetry to the spatio-temporal replication program. Eur. Phys. J. E 35, 92 (2012). https://doi.org/10.1140/epje/i2012-12092-y
Received:
Revised:
Accepted:
Published:
DOI: https://doi.org/10.1140/epje/i2012-12092-y