EVIDENCE FOR EROSION OF MOUSE CPG ISLANDS DURING MAMMALIAN EVOLUTION

In housekeeping and many tissue-specific genes, the promoter is embedd ed in a so-called CpG island. We have compared the available human and mouse DNA sequences with respect to their CpG island properties. Whil e mouse sequences showed a simple gradient distribution of G + C conte nt and CpG densities, man had a distinct peak of sequences with typica l CpG island characteristics. Pairwise comparison of 23 orthologous ge nes revealed that mouse almost always had a less pronounced CpG island than man, or none at all. In both species the requirements for a func tional CpG island may be similar in that most DNA regions with a densi ty of six or more CpG per 100 bp remain unmethylated. However, the mou se has apparently experienced more accidental CpG island methylation, suggested by local TpG and CpA excess. We propose that: (1) in mouse t he CpG islands do not represent the ancestral state but have been erod ed during evolution, and (2) this erosion may be related to the mouse' s small body mass and short life-span, allowing for a more relaxed con trol of gene activity.