Interconnected Codons: Unravelling the Epigenetic Significance of Flanking Sequences in CpG Dyads

Hypothesizing that CpG codon dyads, formed by consecutive codons containing a cytosine-guanine pair (NNC-GNN), may play a crucial role in gene function, we conducted an extensive analysis to investigate their distribution and conservation within mammalian genes. Our findings reveal that genes characterized by a high density of CpG codon dyads are notably associated with homeobox domains and RNA polymerase II transcription factors. Conversely, genes exhibiting low CpG codon dyad density have links to DNA damage repair and mitosis. Importantly, our study identifies a re-markable increase in expressed genes that harbor CpG during embryonic development, suggesting their potential involvement in gene regulation at these developmental stages. These results under-score the functional significance of CpG codon dyads in DNA methylation and gene expression, fur-ther demonstrating the coevolution of consecutive codons and their contribution to codon usage bias.