Date Published: July 11, 2007
Publisher: Public Library of Science
Author(s): Clara S.M. Tang, Richard J. Epstein, Guillaume Bourque. http://doi.org/10.1371/journal.pone.0000603
Abstract: Promoter-associated CpG islands (PCIs) mediate methylation-dependent gene silencing, yet tend to co-locate to transcriptionally active genes. To address this paradox, we used data mining to assess the behavior of PCI-positive (PCI+) genes in the human genome.
Partial Text: Evolution of biological complexity involves an environmentally-regulated balance between genetic conservation and variation –. Phylogenetic leaps favoring speciation of higher organisms include the evolution of introns and DNA methylation , . A more recent innovation is that of promoter-associated CpG islands (PCIs)  which, when methylated, mediate transcriptional repression and/or chromatin condensation . About 60% of human genes contain PCIs , most of which are unmethylated , . Such PCIs are more common in widely-expressed (housekeeping) genes , supporting the view that non-methylated PCIs actively maintain gene transcription , .
There are three central findings of this study. First, there exists an AT-rich ‘second peak’ of PCI+ genes which, when compared with the GC-rich peak of housekeeping-like PCI+ genes, is characterized by lower transcriptional activity, higher intron number and length, and higher evolutionary rate. We propose that the AT-rich subset has arisen from the GC-rich subset of PCI+ genes via progressive loss of negative selection pressure, accompanied by progressive PCI methylation.