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MBE Advance Access originally published online on June 24, 2007
Molecular Biology and Evolution 2007 24(9):1991-2000; doi:10.1093/molbev/msm128
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© The Author 2007. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Research Articles

Features and Trend of Loss of Promoter-Associated CpG Islands in the Human and Mouse Genomes

Cizhong Jiang*,1, Leng Han{dagger},{ddagger},1, Bing Su{dagger}, Wen-Hsiung Li§ and Zhongming Zhao*

* Department of Psychiatry and Center for the Study of Biological Complexity, Virginia Commonwealth University, Richmond, Virginia, USA
{dagger} Key Laboratory of Cellular and Molecular Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China
{ddagger} Graduate School, Chinese Academy of Sciences, Beijing, China
§ Department of Ecology and Evolution, University of Chicago, Chicago, Illinois, USA

E-mail: zzhao{at}vcu.edu.

Accepted for publication June 18, 2007.

CpG islands (CGIs) are often considered as gene markers, but the number of CGIs varies among mammalian genomes that have similar numbers of genes. In this study, we investigated the distribution of CGIs in the promoter regions of 3,197 human-mouse orthologous gene pairs and found that the mouse genome has notably fewer CGIs in the promoter regions and less pronounced CGI characteristics than does the human genome. We further inferred CGI's ancestral state using the dog genome as a reference and examined the nucleotide substitution pattern and the mutational direction in the conserved regions of human and mouse CGIs. The results reveal many losses of CGIs in both genomes but the loss rate in the mouse lineage is two to four times the rate in the human lineage. We found an intriguing feature of CGI loss, namely that the loss of a CGI usually starts from erosion at the both edges and gradually moves towards the center. We found functional bias in the genes that have lost promoter-associated CGIs in the human or mouse lineage. Finally, our analysis indicates that the association of CGIs with housekeeping genes is not as strong as previously estimated. Our study provides a detailed view of the evolution of promoter-associated CGIs in the human and mouse genomes and our findings are helpful for understanding the evolution of mammalian genomes and the role of CGIs in gene function.

Key Words: CpG island evolution • promoter • DNA methylation • functional bias • human • mouse


1 These authors contributed equally to this work

Naoko Takezaki, Associate Editor


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