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.