5mC and 6mA DNA methylation in eukaryotic genomes

DNA methylation events, including 5-methylcytosine (5mC) and N⁶-methyladenine (6mA), represent key epigenetic marks with distinct roles across eukaryotic genomes. Although traditionally viewed as fundamentally divergent, emerging evidence, especially studies on 6mA, reveals striking mechanistic parallels between 5mC and 6mA. In this review, we provide a systematic comparison of the similarities and differences between these two types of DNA methylation, focusing on their genomic distributions, methylation pathways, transcriptional contributions, crosstalk with other epigenetic marks, and evolutionary implications, thereby highlighting their pivotal roles in shaping eukaryotic genomes. By integrating these perspectives, this review emphasizes the fundamental principles shared by these two forms of DNA methylation and offers new insights into their potential roles in eukaryotic evolution.