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Genome Biology and Evolution Advance Access originally published online on August 3, 2009
Genome Biology and Evolution (2009) Vol. 2009:189; doi:10.1093/gbe/evp024 published on August 6, 2009
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© 2009 The Authors
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Long-Range Bidirectional Strand Asymmetries Originate at CpG Islands in the Human Genome

Paz Polak and Peter F. Arndt

Max Planck Institute for Molecular Genetics, Berlin, Germany

E-mail: polak{at}molgen.mpg.de.


  Abstract

In the human genome, CpG islands (CGIs), which are GC- and CpG-rich sequences, are associated with transcription starting sites (TSSs); in addition, there is evidence that CGIs harbor origins of bidirectional replication (OBRs) and are preferred sites for heteroduplex formation during recombination. Transcription, replication, and recombination processes are known to induce specific mutational patterns in various genomes, and therefore, these patterns are expected to be found around CGIs. We use triple alignments of human, chimp, and macaque to compute the rates of nucleotide substitutions in up to 1 Mbps long intergenic regions on both sides of CGIs. Our analysis revealed that around a CGI there is an asymmetry between complementary substitution rates that is similar to the one that found around the OBR in bacteria. We hypothesize that these asymmetries are induced by differences in the replication of the leading and lagging strand and that a significant number of CGIs overlap OBRs. Within CGIs, we observed a mutational signature of GC-biased gene conversion that is associated with recombination. We suggest that recombination has played a major role in the creation of CGIs.

Keywords: CpG islands, strand asymmetries, origin of bi-directional replication, recombination, biased gene conversion

Accepted July 22, 2009

Eugene Koonin, Associate Editor


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