Format

Send to

Choose Destination
See comment in PubMed Commons below
PLoS One. 2007 Jul 11;2(7):e603.

A structural split in the human genome.

Author information

1
Laboratory of Computational Oncology, Department of Medicine, University of Hong Kong, Pokfulam, Hong Kong, Hong Kong.

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.

PMID:
17622348
PMCID:
PMC1904255
DOI:
10.1371/journal.pone.0000603
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Support Center