Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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

Abstract

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.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Recent HGT is enriched in the human microbiome across all phylogenetic distances.
Figure 2: Ecology is the dominant force shaping recent HGT in the human microbiome.
Figure 3: HGT is ecologically structured by functional class and at multiple spatial scales.
Figure 4: Gene exchange is ecologically structured by oxygen tolerance and pathogenicity.

Similar content being viewed by others

References

  1. Ochman, H., Lawrence, J. G. & Groisman, E. A. Lateral gene transfer and the nature of bacterial innovation. Nature 405, 299–304 (2000)

    Article  ADS  CAS  Google Scholar 

  2. Koonin, E. V., Makarova, K. S. & Aravind, L. Horizontal gene transfer in prokaryotes: quantification and classification. Annu. Rev. Microbiol. 55, 709–742 (2011)

    Article  Google Scholar 

  3. Chen, J. & Novick, R. P. Phage-mediated intergeneric transfer of toxin genes. Science 323, 139–141 (2009)

    Article  ADS  CAS  Google Scholar 

  4. Lester, C. H., Frimodt-Moller, N., Sorensen, T. L., Monnet, D. L. & Hammerum, A. M. In vivo transfer of the vanA resistance gene from an Enterococcus faecium isolate of animal origin to an E. faecium isolate of human origin in the intestines of human volunteers. Antimicrob. Agents Chemother. 50, 596–599 (2006)

    Article  CAS  Google Scholar 

  5. Hehemann, J.-H. et al. Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota. Nature 464, 908–912 (2010)

    Article  ADS  CAS  Google Scholar 

  6. Gill, S. R. et al. Metagenomic analysis of the human distal gut microbiome. Science 312, 1355–1359 (2006)

    Article  ADS  CAS  Google Scholar 

  7. Round, J. L. & Mazmanian, S. K. The gut microbiota shapes intestinal immune responses during health and disease. Nature Rev. Immunol. 9, 313–323 (2009)

    Article  CAS  Google Scholar 

  8. Xavier, R. J. & Podolsky, D. K. Unravelling the pathogenesis of inflammatory bowel disease. Nature 448, 427–434 (2007)

    Article  ADS  CAS  Google Scholar 

  9. Ley, R. E., Turnbaugh, P. J., Klein, S. & Gordon, J. I. Microbial ecology: human gut microbes associated with obesity. Nature 444, 1022–1023 (2006)

    Article  ADS  CAS  Google Scholar 

  10. Xu, J. et al. Evolution of symbiotic bacteria in the distal human intestine. PLoS Biol. 5, e156 (2007)

    Article  Google Scholar 

  11. Lawrence, J. G. & Hendrickson, H. Lateral gene transfer: when will adolescence end? Mol. Microbiol. 50, 739–749 (2003)

    Article  CAS  Google Scholar 

  12. Thomas, C. M. & Nielsen, K. M. Mechanisms of, and barriers to, horizontal gene transfer between bacteria. Nature Rev. Microbiol. 3, 711–721 (2005)

    Article  CAS  Google Scholar 

  13. Gogarten, J. P., Doolittle, W. F. & Lawrence, J. G. Prokaryotic evolution in light of gene transfer. Mol. Biol. Evol. 19, 2226–2238 (2002)

    Article  CAS  Google Scholar 

  14. Mazodier, P. & Davies, J. Gene transfer between distantly related bacteria. Annu. Rev. Genet. 25, 147–171 (2011)

    Article  Google Scholar 

  15. Tuller, T. et al. Association between translation efficiency and horizontal gene transfer within microbial communities. Nucleic Acids Res. 39, 1–13 (2011)

    Article  Google Scholar 

  16. Jain, R., Rivera, M. C. & Lake, J. A. Horizontal gene transfer among genomes: the complexity hypothesis. Proc. Natl Acad. Sci. USA 96, 3801–3806 (1999)

    Article  ADS  CAS  Google Scholar 

  17. Boucher, Y. et al. Local mobile gene pools rapidly cross species boundaries to create endemicity within global Vibrio cholerae populations. mBio 2 (2). e00335–10 10.1128/mBio.00335-10 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kumarasamy, K. K. et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect. Dis. 10, 597–602 (2010)

    Article  CAS  Google Scholar 

  19. Aravind, L., Tatusov, R. L., Wolf, Y. I., Walker, D. R. & Koonin, E. V. Evidence for massive gene exchange between archaeal and bacterial hyperthermophiles. Trends Genet. 14, 442–444 (1998)

    Article  CAS  Google Scholar 

  20. Caro-Quintero, A. et al. Unprecedented levels of horizontal gene transfer among spatially co-occurring Shewanella bacteria from the Baltic Sea. ISME J. 5, 131–140 (2010)

    Article  Google Scholar 

  21. Ochman, H., Elwyn, S. & Moran, N. A. Calibrating bacterial evolution. Proc. Natl Acad. Sci. USA 96, 12638–12643 (1999)

    Article  ADS  CAS  Google Scholar 

  22. Ochman, H. & Wilson, A. C. Evolution in bacteria: evidence for a universal substitution rate in cellular genomes. J. Mol. Evol. 26, 74–86 (1987)

    Article  ADS  CAS  Google Scholar 

  23. Kim, K. S. Pathogenesis of bacterial meningitis: from bacteraemia to neuronal injury. Nature Rev. Neurosci. 4, 376–385 (2003)

    Article  CAS  Google Scholar 

  24. Clatworthy, A. E., Pierson, E. & Hung, D. T. Targeting virulence: a new paradigm for antimicrobial therapy. Nature Chem. Biol. 3, 541–548 (2007)

    Article  CAS  Google Scholar 

  25. DeSantis, T. Z. et al. Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB. Appl. Environ. Microbiol. 72, 5069–5072 (2006)

    Article  CAS  Google Scholar 

  26. Altschul, S. F., Gish, W., Miller, W., Myers, E. W. & Lipman, D. J. Basic local alignment search tool. J. Mol. Biol. 215, 403–410 (1990)

    Article  CAS  Google Scholar 

  27. Markowitz, V. M. et al. The integrated microbial genomes (IMG) system. Nucleic Acids Res. 34, D344–D348 (2006)

    Article  CAS  Google Scholar 

  28. Edgar, R. C. Search and clustering orders of magnitude faster than BLAST. Bioinformatics 26, 2460–2461 (2010)

    Article  CAS  Google Scholar 

  29. Liu, B. & Pop, M. ARDB—Antibiotic Resistance Genes Database. Nucleic Acids Res. 37, D443–D447 (2009)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

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

Authors and Affiliations

Authors

Contributions

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.

Corresponding author

Correspondence to Eric J. Alm.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

The file contains Supplementary Methods, Supplementary References, Supplementary Figures 1-6 with legends and Supplementary Tables 1-7. (PDF 1916 kb)

Supplementary Data 1

This file contains the Metadata for HGT analysis (TXT 168 kb)

Supplementary Data 2

This file contains the HGT FSTA sequences. (ZIP 9391 kb)

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Cite this article

Smillie, C., Smith, M., Friedman, J. et al. Ecology drives a global network of gene exchange connecting the human microbiome. Nature 480, 241–244 (2011). https://doi.org/10.1038/nature10571

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature10571

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing