MBE Advance Access published online on November 27, 2007
Molecular Biology and Evolution, doi:10.1093/molbev/msm261
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Research Article |
Exponential Decay of GC-content Detected by Strand-symmetric Substitution Rates Influences the Evolution of Isochore Structure
1 Department of Computer Science and Systems Analysis, Miami University, Ohio, USA
2 Department of Microbiology, Miami University, Ohio, USA
3 Center for Comparative Genomics and Bioinformatics, Pennsylvania State University, Pennsylvania, USA
4 Institute of Chemistry, Karl-Franzens University Graz, Graz, Austria
5 Institute for Theoretical Biology, Humboldt University, Berlin, Germany
Corresponding Author: John E. Karro, Wartk 506B, Penn. State University, University Park, PA 16802, USA, Phone: 814-865-4747, Fax: 814-863-6699, email: jkarro{at}acm.org
Received for publication May 31, 2007. Revision received October 26, 2007. Accepted for publication November 20, 2007.
The distribution of guanine and cytosine nucleotides throughout a genome, or the GC-content, is associated with numerous features in mammals; understanding the pattern and evolutionary history of GC-content is crucial to our annotation of the genome. The local GC-content is decaying towards an equilibrium point, but the causes and rates of this decay, as well as the value of the equilibrium point, remain topics of debate. By comparing the results of two methods for estimating local substitution rates we identify 620 Mb of the human genome in which the rates of the various types of nucleotide substitutions are the same on both strands. These strand-symmetric regions show an exponential decay of local GC-content at a pace determined by local substitution rates. DNA segments subjected to higher rates experience disproportionately accelerated decay and are AT-rich, whereas segments subjected to lower rates decay more slowly and are GC-rich. Although we are unable to draw any conclusions about causal factors, the results support the hypothesis proposed by Khelifi etal.(2006) that the isochore structure has been reshaped over time. If rate variation were a determining factor, then the current isochore structure of mammalian genomes could result from the local differences in substitution rates. We predict that strand-symmetric portions of the human genome will stabilize at an average GC-content of 30% (considerably less than the current 42%), thus confirming that the human genome has not yet reached equilibrium.
Key Words: GC content • Isochore decay • Neutral substitution rates • Strand symmetry • Genomic equilibrium
* Authors contributed equally.
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