Divergence of CpG island promoters: A consequence or cause of evolution?

Abstract

CpG islands (CGIs) are CG-rich stretches in the genome that are concentrated near the transcription start sites (TSS) of genes. Genes that possess CGIs, such as the housekeeping genes, are often highly expressed in multiple tissues. Indeed, CGIs are enriched in approximately half of the promoters in humans and mice, suggesting an important role for CpG islands in mammalian transcriptional regulation. Interestingly, accumulation of CpG islands at TSS appears to be a vertebrate specific genomic feature, which implicates a link between CpG islands and evolution. However, it remains unclear whether the association of CGIs to gene promoters is a cause or consequence of evolution. In the present study, we have addressed this question by analyzing nine species including invertebrates, chordates and vertebrates, using bioinformatics based techniques. Our results indicate that CGIs arose at TSS as a "consequence" of warm-blooded vertebrate evolution, presumably for efficient regulation of transcription in a larger genome. Furthermore, we reveal that CGIs could have functioned as a direct "cause" of evolution among the warm-blooded vertebrates, such as contributing to the gain of placenta, which is a hallmark of eutherian mammals. Elucidation of the origin and functions of CpG islands and the process of their convergence into transcription start sites of genes will pave the way for a greater understanding of the roles for CGIs in gene expression, development and reprogramming of the genome.