DNA methylation is an epigenetic modification, influenced by both genetic and environmental variation, that plays a key role in transcriptional regulation and many organismal phenotypes. Although patterns of DNA methylation have been shown to differ between human populations, it remains to be determined how epigenetic diversity relates to the patterns of genetic and gene expression variation at a global scale. Here we measured DNA methylation at 485,000 CpG sites in five diverse human populations, and analysed these data together with genome-wide genotype and gene expression data. We found that population-specific DNA methylation mirrors genetic variation, and has greater local genetic control than mRNA levels. We estimated the rate of epigenetic divergence between populations, which indicates far greater evolutionary stability of DNA methylation in humans than has been observed in plants. This study provides a deeper understanding of worldwide patterns of human epigenetic diversity, as well as initial estimates of the rate of epigenetic divergence in recent human evolution.

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O.C. and M.W.F. acknowledge support from the Morrison Institute for Population and Resource Studies at Stanford and the Stanford Centre for Computational, Evolutionary and Human Genomics. B.M.H. acknowledges support from NIH grant 3R01HG003229 to C. B. Bustamante. M.S.K. is a Senior Fellow of the Canadian Institute for Advanced Research and the Canada Research Chair in Social Epigenetics. We thank members of the Feldman Laboratory, in particular N. Creanza and J. Granka, for helpful discussions, and M. Jones for comments. This research was done using resources provided by the Open Science Grid, which is supported by the National Science Foundation award 1148698, and the US Department of Energy’s Office of Science.

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Author notes

    • Oana Carja

    Present address: Department of Biology, University of Pennsylvania, Philadelphia, PA, 19104, USA


  1. Department of Biology, Stanford University, Stanford, CA, 94305, USA

    • Oana Carja
    • , Marcus W. Feldman
    •  & Hunter B. Fraser
  2. Centre for Molecular Medicine and Therapeutics, BC Children’s Hospital Research Institute, University of British Columbia, Vancouver, BC, V5Z 4H4, Canada

    • Julia L. MacIsaac
    • , Sarah M. Mah
    •  & Michael S. Kobor
  3. Department of Medical Genetics, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada

    • Julia L. MacIsaac
    • , Sarah M. Mah
    •  & Michael S. Kobor
  4. Department of Ecology and Evolution, Stony Brook University, Stony Brook, NY, 11790, USA

    • Brenna M. Henn


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O.C., B.M.H., M.S.K., M.W.F. and H.B.F. designed the study. J.L.M., S.M.M. and M.S.K. generated the methylation data set. O.C. analysed the data and O.C., B.M.H., M.S.K., M.W.F. and H.B.F. wrote the manuscript.

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The authors declare no competing financial interests.

Corresponding author

Correspondence to Oana Carja.

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