Comparative analysis reveals epigenomic evolution related to species traits and genomic imprinting in mammals

DNA methylation is an epigenetic modification that plays a crucial role in various regulatory processes, including gene expression regulation, trans-posable element repression, and genomic imprinting. However, most studies on DNA methylation have been conducted in humans and other model species, whereas the dynamics of DNA methylation across mammals remain poorly explored, limiting our understanding of epigenomic evolution mammals and the evolutionary impacts of conserved and lineage-specific DNA methylation. Here, we generated and gathered comparative epige-nomic data from 13 mammalian species, including two marsupial species, to demonstrate that DNA methylation plays critical roles in several aspects of gene evolution and species trait evolution. We found that the species -spe-cific DNA methylation of promoters and noncoding elements correlates with species-specific traits such as body patterning, indicating that DNA methyl-ation might help establish or maintain interspecies differences in gene regu-lation that shape phenotypes. For a broader view, we investigated the evolu-tionary histories of 88 known imprinting control regions across mammals to identify their evolutionary origins. By analyzing the features of known and newly identified potential imprints in all studied mammals, we found that genomic imprinting may function in embryonic development through the binding of specific transcription factors. Our findings show that DNA methyl-ation and the complex interaction between the genome and epigenome have significant impact on mammalian evolution, suggesting that evolutionary epigenomics should be incorporated to develop a unified evolutionary theory.