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RESEARCH ARTICLE Long-Range Bidirectional Strand Asymmetries Originate at CpG Islands in the
 

Summary: RESEARCH ARTICLE
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
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.
Introduction
Even though CpG islands (CGIs) have been suggested
more than decade ago to colocalize with origins of replica-
tion (ORIs; Delgado et al. 1998), there has not been a study
of the impact of this association on the mutational patterns

  

Source: Arndt, Peter - Max-Planck-Institut für molekulare Genetik
Spang, Rainer - Computational Molecular Biology Group, Max-Planck-Institut für molekulare Genetik

 

Collections: Biology and Medicine; Biotechnology; Computer Technologies and Information Sciences; Physics