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Worldwide patterns of human epigenetic variation

Nature Ecology & Evolution volume 1, pages 1577–1583 (2017)Cite this article

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Abstract

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.

Human evolutionary history has left a strong signature on worldwide patterns of genetic variation1,2,3. Principal component analyses (PCA) and related methods reveal patterns of genetic diversity within and across populations, in particular population stratification and admixture. The first two principal components of a single nucleotide polymorphism (SNP) genotype matrix are often sufficient to compare the ancestries of different human populations and to show how genetic similarity between populations varies with geographic distance2,4,5,6,7.

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Fig. 1: Context of genome-wide population structure.
Fig. 2: Population specificity of CpG methylation.
Fig. 3: Structure of epigenome-wide population differences.
Fig. 4: Epigenetic divergence as a linear function of genetic distance.

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Acknowledgements

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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  1. Oana Carja

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

Authors and Affiliations

  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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Contributions

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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Correspondence to Oana Carja.

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Supplementary Figures 1,2; Supplementary Tables 1–4

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Carja, O., MacIsaac, J.L., Mah, S.M. et al. Worldwide patterns of human epigenetic variation. Nat Ecol Evol 1, 1577–1583 (2017). https://doi.org/10.1038/s41559-017-0299-z

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