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Differential DNA methylation reveals metabolic adaptation in recent modern human evolution

ABSTRACT: The advent of agriculture approximately 12,000 years ago heralded significant shifts in human diets, lifestyles, and population densities, presenting new selective pressures on human populations. Recent studies have focused on genetic adaptations to these changes, but the role of epigenetic mechanisms, particularly DNA methylation, in human evolution remains underexplored. Here, we reconstructed whole-genome DNA methylation maps for 39 ancient human bone samples spanning the past 11,000 years, and identified genomic regions displaying methylation changes across time. To reveal potential regulatory sequences within these differentially methylated regions (DMRs), we further mapped enhancers in human bone using Chromatin Immunoprecipitation Sequencing (ChIP-Seq) for H3K27 acetylation (H3K27ac). Globally, our analysis revealed increased DNA methylation, particularly around promoters and transcription start sites (TSS), in the more recent samples, suggesting recent evolutionary epigenetic adaptation. Among the DMRs, we identified 49 enhancers showing significant negative correlation with sample age. Enrichment analysis of the annotated genes point to metabolic-related phenotypes. Our findings suggest that DNA methylation changes in regulatory regions may have played a significant role in human adaptation. This study highlights the importance of considering epigenetic mechanisms in the study of recent human evolution and suggests that environmental changes, such as diet, can induce epigenetic adaptations.

ORGANISM(S): Homo sapiens

PROVIDER: GSE269893 | GEO | 2025/12/31

REPOSITORIES: GEO

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