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Genomic variation landscape of the human gut microbiome

Nature volume 493, pages 45–50 (2013)Cite this article

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Abstract

Whereas large-scale efforts have rapidly advanced the understanding and practical impact of human genomic variation, the practical impact of variation is largely unexplored in the human microbiome. We therefore developed a framework for metagenomic variation analysis and applied it to 252 faecal metagenomes of 207 individuals from Europe and North America. Using 7.4 billion reads aligned to 101 reference species, we detected 10.3 million single nucleotide polymorphisms (SNPs), 107,991 short insertions/deletions, and 1,051 structural variants. The average ratio of non-synonymous to synonymous polymorphism rates of 0.11 was more variable between gut microbial species than across human hosts. Subjects sampled at varying time intervals exhibited individuality and temporal stability of SNP variation patterns, despite considerable composition changes of their gut microbiota. This indicates that individual-specific strains are not easily replaced and that an individual might have a unique metagenomic genotype, which may be exploitable for personalized diet or drug intake.

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Figure 1: Genomic variation statistics for 101 gut microbial species prevalent in 252 samples from 207 individuals.
Figure 2: pN/pS ratios of 66 dominant species reveal more variation between species than between individuals.
Figure 3: Individuality and temporal stability of genomic variation patterns.
Figure 4: Inter-continental comparison of gut microbial species.

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Data deposits

Single nucleotide polymorphism data have been submitted to dbSNP under accession numbers ss539238913–ss549853572.

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Acknowledgements

The authors are grateful to J. Korbel and the members of the Bork group at EMBL for discussions and assistance, especially S. Powell for performing some of the computations. We thank the EMBL IT core facility and Y. Yuan for managing the high-performance computing resources. We would like to thank J. I. Gordon for providing three of the samples used. We are also grateful to the European MetaHIT consortium and the NIH Common Fund Human Microbiome Project Consortium for generating and making available the data sets used in this study. The research leading to these results has received funding from EMBL, the European Community’s Seventh Framework Programme via the MetaHIT (HEALTH-F4-2007-201052) and IHMS (HEALTH-F4-2010-261376) grants as well as from the National Institutes of Health grants U54HG003079 and U54HG004968.

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Author notes

  1. Siegfried Schloissnig, Manimozhiyan Arumugam and Shinichi Sunagawa: These authors contributed equally to this work.

Authors and Affiliations

  1. European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany ,

    Siegfried Schloissnig, Manimozhiyan Arumugam, Shinichi Sunagawa, Julien Tap, Ana Zhu, Alison Waller, Daniel R. Mende, Jens Roat Kultima & Peer Bork

  2. The Genome Institute, Washington University School of Medicine, 4444 Forest Park Avenue, St Louis, Missouri 63108, USA ,

    Makedonka Mitreva, John Martin, Karthik Kota & George M. Weinstock

  3. Division of Genetics, Department of Medicine, Brigham & Women’s Hospital & Harvard Medical School, Boston, 02115, Massachusetts, USA

    Shamil R. Sunyaev

  4. Max Delbrück Centre for Molecular Medicine, Berlin, D-13092, Germany

    Peer Bork

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  1. Siegfried Schloissnig
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Contributions

P.B. and G.M.W. conceived the study. P.B., M.A., G.M.W. and S.R.S. designed the analyses. Si.S., Sh.S., M.A., M.M., J.T., A.Z., A.W., D.R.M., J.R.K., J.M. and K.K. performed the analyses. M.A., Sh.S., Si.S. and P.B. wrote the manuscript. All authors read and approved the manuscript.

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Correspondence to George M. Weinstock or Peer Bork.

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The authors declare no competing financial interests.

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This file contains Supplementary Methods and Notes, additional references, Supplementary Figures 1-8 and legends for Supplementary Tables 1-15. (PDF 1947 kb)

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Schloissnig, S., Arumugam, M., Sunagawa, S. et al. Genomic variation landscape of the human gut microbiome. Nature 493, 45–50 (2013). https://doi.org/10.1038/nature11711

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