Year: 2007
Type: article
Abstract: BACKGROUND: 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. RESULTS: PCI+ genes exhibit a bimodal distribution: (1) a 'housekeeping-like' subset characterized by higher GC content and lower intron length/number, and (2) a 'pseudogene paralog' subset characterized by lower GC content and higher intron length/number (p<0.001). These subsets are functionally distinguishable, with the former gene group characterized by higher expression levels and lower evolutionary rate (p<0.001). PCI-negative (PCI-) genes exhibit higher evolutionary rate and narrower expression breadth than PCI+ genes (p<0.001), consistent with more frequent tissue-specific inactivation. CONCLUSIONS: Adaptive evolution of the human genome appears driven in part by declining transcription of a subset of PCI+ genes, predisposing to both CpG-->TpA mutation and intron insertion. We propose a model of evolving biological complexity in which environmentally-selected gains or losses of PCI methylation respectively favor positive or negative selection, thus polarizing PCI+ gene structures around a genomic core of ancestral PCI- genes.
Source: PLoS ONE
Authors: Clara S.M. Tang, Richard J. Epstein
Institution: University of Hong Kong
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,382
OpenAlex ID: W2052126979