Genome-Wide 6mA Map Unveils Epigenetic Adaptation in Deep-Sea Limpet

How animals thrive in extreme deep-sea environments remains a key question in marine evolutionary biology. While adaptation is often studied through the lens of genetic sequence, the epigenetic mechanisms that allow for phenotypic plasticity and rapid environmental response in these organisms remain a major "black box". DNA N6-methyladenine (6mA) is an emerging epigenetic mark in eukaryotes, but its presence and role in deep-sea animals remain unknown. Here, we present the first genome-wide map of DNA 6mA in a deep-sea animal, the cold seep limpet Bathyacmaea lactea, generated using PacBio single-molecule real-time (SMRT) sequencing. We identified 281,772 high-confidence 6mA sites, comprising ~0.13% of all adenines in the genome. Over 60% of genes harbor 6mA, with sites significantly enriched in exons. Integration with RNA-seq data revealed that gene body 6mA correlates with active transcription, whereas promoter 6mA is associated with gene repression. Genes with abundant 6mA are enriched in pathways related to energy metabolism, protein homeostasis, and osmoregulation, suggesting that 6mA methylation may facilitate adaptation to high pressure, low temperature, and dark deep-sea conditions. Our findings uncover 6mA as a component of the B. lactea epigenome and provide novel insights into epigenetic regulation under extreme deep-sea environments.