It has been envisaged that CpG islands are often observed near the 
transcriptional start sites (TSS) of housekeeping genes. However, neither the 
precise positions of CpG islands relative to TSS of genes nor the correlation 
between the presence of the CpG islands and the expression specificity of these 
genes is well-understood. Using thousands of sequences with known TSS in human 
and mouse, we found that there is a clear peak in the distribution of CpG 
islands around TSS in the genes of these two species. Thus, we classified human 
(mouse) genes into 6600 (2948) CpG+ genes and 2619 (1830) CpG- ones, based on 
the presence of a CpG island within the -100: +100 region. We estimated the 
degree of each gene being a housekeeper by the number of cDNA libraries where 
its ESTs were detected. Then, the tendency that a gene lacking CpG islands 
around its TSS is expressed with a higher degree of tissue specificity turned 
out to be evolutionarily conserved. We also confirmed this tendency by analyzing 
the gene ontology annotation of classified genes. Since no such clear 
correlation was found in the control data (mRNAs, pre-mRNAs, and chromosome 
banding pattern), we concluded that the effect of a CpG island near the TSS 
should be more important than the global GC content of the region where the gene 
resides.