Letter | Published:

Ecology drives a global network of gene exchange connecting the human microbiome

Nature volume 480, pages 241244 (08 December 2011) | Download Citation


Horizontal gene transfer (HGT), the acquisition of genetic material from non-parental lineages, is known to be important in bacterial evolution1,2. In particular, HGT provides rapid access to genetic innovations, allowing traits such as virulence3, antibiotic resistance4 and xenobiotic metabolism5 to spread through the human microbiome. Recent anecdotal studies providing snapshots of active gene flow on the human body have highlighted the need to determine the frequency of such recent transfers and the forces that govern these events4,5. Here we report the discovery and characterization of a vast, human-associated network of gene exchange, large enough to directly compare the principal forces shaping HGT. We show that this network of 10,770 unique, recently transferred (more than 99% nucleotide identity) genes found in 2,235 full bacterial genomes, is shaped principally by ecology rather than geography or phylogeny, with most gene exchange occurring between isolates from ecologically similar, but geographically separated, environments. For example, we observe 25-fold more HGT between human-associated bacteria than among ecologically diverse non-human isolates (P = 3.0 × 10−270). We show that within the human microbiome this ecological architecture continues across multiple spatial scales, functional classes and ecological niches with transfer further enriched among bacteria that inhabit the same body site, have the same oxygen tolerance or have the same ability to cause disease. This structure offers a window into the molecular traits that define ecological niches, insight that we use to uncover sources of antibiotic resistance and identify genes associated with the pathology of meningitis and other diseases.

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This work was supported by National Science Foundation awards 0918333 and 0936234 to E.J.A., and by the Department of Energy’s ENIGMA Scientific Focus Area. This work is part of the National Institutes of Health Human Microbiome Project.

Author information

Author notes

    • Chris S. Smillie
    •  & Mark B. Smith

    These authors contributed equally to this work.


  1. Computational and Systems Biology Initiative, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

    • Chris S. Smillie
    •  & Jonathan Friedman
  2. Microbiology Graduate Program, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

    • Mark B. Smith
  3. Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

    • Otto X. Cordero
    •  & Eric J. Alm
  4. Society of Fellows, Harvard University, Cambridge, Massachusetts 02138, USA

    • Lawrence A. David
  5. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

    • Eric J. Alm
  6. Broad Institute, Cambridge, Massachusetts 02139, USA

    • Eric J. Alm


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C.S.S., M.B.S. and E.J.A. conceived the study. C.S.S., M.B.S., J.F. and E.J.A. analysed the data. C.S.S., M.B.S., J.F., O.X.C., L.A.D. and E.J.A. provided conceptual insight. C.S.S., M.B.S. and E.J.A. prepared the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Eric J. Alm.

Supplementary information

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    Supplementary Information

    The file contains Supplementary Methods, Supplementary References, Supplementary Figures 1-6 with legends and Supplementary Tables 1-7.

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    Supplementary Data 1

    This file contains the Metadata for HGT analysis

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    Supplementary Data 2

    This file contains the HGT FSTA sequences.

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