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The Landscape of Genetic Content in the Human Microbiome

29 Pages Posted: 26 Feb 2019 Sneak Peek Status: Published

See all articles by Braden T. Tierney

Braden T. Tierney

Joslin Diabetes Center - Section on Pathophysiology and Molecular Pharmacology; Joslin Diabetes Center - Section on Islet Cell and Regenerative Biology; Harvard University - Department of Microbiology and Immunobiology; Harvard University - Department of Biomedical Informatics

Zhen Yang

Joslin Diabetes Center - Section on Pathophysiology and Molecular Pharmacology; Joslin Diabetes Center - Section on Islet Cell and Regenerative Biology; Harvard University - Department of Microbiology and Immunobiology; University of Waterloo - Department of Combinatorics and Optimization

Jacob M. Luber

Joslin Diabetes Center - Section on Pathophysiology and Molecular Pharmacology; Joslin Diabetes Center - Section on Islet Cell and Regenerative Biology; Harvard University - Department of Microbiology and Immunobiology; Harvard University - Department of Biomedical Informatics

Marc Beaudin

Joslin Diabetes Center - Section on Pathophysiology and Molecular Pharmacology; Joslin Diabetes Center - Section on Islet Cell and Regenerative Biology; Harvard University - Department of Microbiology and Immunobiology; University of Alberta - Faculty of Medicine & Denistry

Marsha C. Wibowo

Joslin Diabetes Center - Section on Pathophysiology and Molecular Pharmacology; Joslin Diabetes Center - Section on Islet Cell and Regenerative Biology; Harvard University - Department of Microbiology and Immunobiology

Christina Baek

University of California, Berkeley - Department of Electrical Engineering & Computer Sciences (EECS)

Chirag J. Patel

Harvard University - Department of Biomedical Informatics

Aleksandar D. Kostic

Joslin Diabetes Center - Section on Pathophysiology and Molecular Pharmacology; Joslin Diabetes Center - Section on Islet Cell and Regenerative Biology; Harvard University - Department of Microbiology and Immunobiology

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Abstract

We have not quantitated the scale of human microbiome genetic diversity, an instrumental task for understanding human-microbe interactions. Here, to do so, we conducted a cross-study meta-analysis of metagenomes from two niches, the mouth and gut, amassing 3,655 samples from 21 studies. We found staggering genetic heterogeneity in our dataset, identifying that 50% of the genes in both datasets were “singletons”, meaning they were unique to specific individuals. We found that singletons arose from individual-specific, instransient, and extremely rare microbial strains. Further, we estimated that the oral and gut microbiomes universally contain 91 and 239 million unique genes, respectively, and that adequately sampling these spaces, such that each new metagenome contains 1% undiscovered genes, will take 6,000 and 20,000 samples. Overall, these results serve as a potential explanation for the large, unexplained heterogeneity observed in microbiome-derived human phenotypes.

Suggested Citation

Tierney, Braden T. and Yang, Zhen and Luber, Jacob M. and Beaudin, Marc and Wibowo, Marsha C. and Baek, Christina and Patel, Chirag J. and Kostic, Aleksandar D., The Landscape of Genetic Content in the Human Microbiome (January 19, 2019). Available at SSRN: https://ssrn.com/abstract=3318927 or http://dx.doi.org/10.2139/ssrn.3318927
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Braden T. Tierney

Joslin Diabetes Center - Section on Pathophysiology and Molecular Pharmacology

One Joslin Place
Boston, MA 02115
United States

Joslin Diabetes Center - Section on Islet Cell and Regenerative Biology

One Joslin Place
Boston, MA 02115
United States

Harvard University - Department of Microbiology and Immunobiology

25 Shattuck St
Boston, MA 02115
United States

Harvard University - Department of Biomedical Informatics

1875 Cambridge Street
Cambridge, MA 02138
United States

Zhen Yang

Joslin Diabetes Center - Section on Pathophysiology and Molecular Pharmacology

One Joslin Place
Boston, MA 02115
United States

Joslin Diabetes Center - Section on Islet Cell and Regenerative Biology

One Joslin Place
Boston, MA 02115
United States

Harvard University - Department of Microbiology and Immunobiology

25 Shattuck St
Boston, MA 02115
United States

University of Waterloo - Department of Combinatorics and Optimization

Waterloo, Ontario N2L 3G1
Canada

Jacob M. Luber

Joslin Diabetes Center - Section on Pathophysiology and Molecular Pharmacology

One Joslin Place
Boston, MA 02115
United States

Joslin Diabetes Center - Section on Islet Cell and Regenerative Biology

One Joslin Place
Boston, MA 02115
United States

Harvard University - Department of Microbiology and Immunobiology

25 Shattuck St
Boston, MA 02115
United States

Harvard University - Department of Biomedical Informatics

1875 Cambridge Street
Cambridge, MA 02138
United States

Marc Beaudin

Joslin Diabetes Center - Section on Pathophysiology and Molecular Pharmacology

One Joslin Place
Boston, MA 02115
United States

Joslin Diabetes Center - Section on Islet Cell and Regenerative Biology

One Joslin Place
Boston, MA 02115
United States

Harvard University - Department of Microbiology and Immunobiology

25 Shattuck St
Boston, MA 02115
United States

University of Alberta - Faculty of Medicine & Denistry

116 St. and 85 Ave
Edmonton, Alberta
Canada

Marsha C. Wibowo

Joslin Diabetes Center - Section on Pathophysiology and Molecular Pharmacology

One Joslin Place
Boston, MA 02115
United States

Joslin Diabetes Center - Section on Islet Cell and Regenerative Biology

One Joslin Place
Boston, MA 02115
United States

Harvard University - Department of Microbiology and Immunobiology

25 Shattuck St
Boston, MA 02115
United States

Christina Baek

University of California, Berkeley - Department of Electrical Engineering & Computer Sciences (EECS)

Berkeley, CA 94720-1712
United States

Chirag J. Patel

Harvard University - Department of Biomedical Informatics

1875 Cambridge Street
Cambridge, MA 02138
United States

Aleksandar D. Kostic (Contact Author)

Joslin Diabetes Center - Section on Pathophysiology and Molecular Pharmacology

One Joslin Place
Boston, MA 02115
United States

Joslin Diabetes Center - Section on Islet Cell and Regenerative Biology

One Joslin Place
Boston, MA 02115
United States

Harvard University - Department of Microbiology and Immunobiology

25 Shattuck St
Boston, MA 02115
United States

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