Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter.
Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page R1
The New Science of Metagenomics: Revealing the Secrets of Our Microbial Planet
THE NEW SCIENCE OF METAGENOMICS
Revealing the Secrets of Our Microbial Planet
Committee on Metagenomics: Challenges and Functional Applications
Board on Life Sciences
Division on Earth and Life Studies
NATIONAL RESEARCH COUNCIL OF THE NATIONAL ACADEMIES
THE NATIONAL ACADEMIES PRESS
Washington, DC
www.nap.edu
OCR for page R2
The New Science of Metagenomics: Revealing the Secrets of Our Microbial Planet
THE NATIONAL ACADEMIES PRESS
500 Fifth Street, NW Washington, DC 20001
NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.
This study was supported by Contract MCB—0544539 between the National Academy of Sciences and the National Science Foundation (NSF), Contract N01-OD-4-2139 between the National Academy of Sciences and the Department of Health and Human Services, National Institutes of Health (NIH), and Contract DE-AT01-05ER64072 between the National Academy of Sciences and the Department of Energy (DOE). The content of this publication does not necessarily reflect the views or policies of NIH, NSF, or DOE, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.
International Standard Book Number-13: 978-0-309-10676-4
International Standard Book Number-10: 0-309-10676-1
Cover: Design by Francesca Moghari; artwork by Nicolle Rager Fuller (www.sayo-art.com).
Additional copies of this report are available from the
National Academies Press,
500 Fifth Street, NW, Lockbox 285, Washington, DC 20055; (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area); Internet, http://www.nap.edu.
Copyright 2007 by the National Academy of Sciences. All rights reserved.
Printed in the United States of America
OCR for page R3
The New Science of Metagenomics: Revealing the Secrets of Our Microbial Planet
THE NATIONAL ACADEMIES
Advisers to the Nation on Science, Engineering, and Medicine
The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Ralph J. Cicerone is president of the National Academy of Sciences.
The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Wm. A. Wulf is president of the National Academy of Engineering.
The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine.
The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Wm. A. Wulf are chair and vice chair, respectively, of the National Research Council.
www.national-academies.org
OCR for page R4
The New Science of Metagenomics: Revealing the Secrets of Our Microbial Planet
This page intentionally left blank.
OCR for page R5
The New Science of Metagenomics: Revealing the Secrets of Our Microbial Planet
COMMITTEE ON METAGENOMICS: CHALLENGES AND FUNCTIONAL APPLICATIONS
JO HANDELSMAN (Cochair),
University of Wisconsin, Madison
JAMES TIEDJE (Cochair),
Michigan State University, East Lansing
LISA ALVAREZ-COHEN,
University of California, Berkeley
MICHAEL ASHBURNER,
University of Cambridge, United Kingdom
ISAAC K. O. CANN,
University of Illinois, Urbana-Champaign
EDWARD F. DELONG,
Massachusetts Institute of Technology, Cambridge
W. FORD DOOLITTLE,
Dalhousie University, Halifax, Nova Scotia, Canada
CLAIRE M. FRASER-LIGGETT,
University of Maryland School of Medicine, Baltimore
ADAM GODZIK,
Burnham Institute for Medical Research, La Jolla, CA
JEFFREY I. GORDON,
Washington University School of Medicine, St. Louis, MO
MARGARET RILEY,
University of Massachusetts, Amherst
MOLLY B. SCHMID,
Keck Graduate Institute, Claremont, CA
Staff
ANN H. REID, Study Director
FRANCES E. SHARPLES, Director,
Board on Life Sciences
ANNE F. JURKOWSKI, Senior Program Assistant
MERC FOX, Program Assistant
NORMAN GROSSBLATT, Senior Editor
OCR for page R6
The New Science of Metagenomics: Revealing the Secrets of Our Microbial Planet
BOARD ON LIFE SCIENCES
KEITH YAMAMOTO (Chair),
University of California, San Francisco
ANN M. ARVIN,
Stanford University School of Medicine, Stanford, CA
JEFFREY L. BENNETZEN,
University of Georgia, Athens
RUTH BERKELMAN,
Emory University, Atlanta, GA
DEBORAH BLUM,
University of Wisconsin, Madison
R. ALTA CHARO,
University of Wisconsin, Madison
JEFFREY L. DANGL,
University of North Carolina, Chapel Hill
PAUL R. EHRLICH,
Stanford University, Stanford, CA
MARK D. FITZSIMMONS,
John D. and Catherine T. MacArthur Foundation, Chicago, IL
JO HANDELSMAN,
University of Wisconsin, Madison
ED HARLOW,
Harvard Medical School, Boston, MA
KENNETH H. KELLER,
University of Minnesota, Minneapolis
RANDALL MURCH,
Virginia Polytechnic Institute and State University, Alexandria
GREGORY A. PETSKO,
Brandeis University, Waltham, MA
MURIEL E. POSTON,
Skidmore College, Saratoga Springs, NY
JAMES REICHMAN,
University of California, Santa Barbara
MARC T. TESSIER-LAVIGNE,
Genentech, Inc., South San Francisco, CA
JAMES TIEDJE,
Michigan State University, East Lansing
TERRY L. YATES,
University of New Mexico, Albuquerque
Staff
FRANCES E. SHARPLES, Director
KERRY A. BRENNER, Senior Program Officer
ANN H. REID, Senior Program Officer
MARILEE K. SHELTON-DAVENPORT, Senior Program Officer
EVONNE P. Y. TANG, Senior Program Officer
ROBERT T. YUAN, Senior Program Officer
ADAM P. FAGEN, Program Officer
ANNA FARRAR, Financial Associate
ANNE F. JURKOWSKI, Senior Program Assistant
TOVA JACOBOVITS, Senior Program Assistant
MERC FOX, Program Assistant
OCR for page R7
The New Science of Metagenomics: Revealing the Secrets of Our Microbial Planet
Acknowledgments
This report has been reviewed in draft form by persons chosen for their diverse perspectives and technical expertise in accordance with procedures approved by the National Research Council’s Report Review Committee. The purpose of the independent review is to provide candid and critical comments that will assist the institution in making the published report as sound as possible and to ensure that the report meets institutional standards of objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We wish to thank the following for their review of the report:
Gary Anderson, Lawrence Berkeley National Laboratory, Berkeley, CA
Jeffrey Dangl, University of North Carolina, Chapel Hill
Julian E. Davies, University of British Columbia, Vancouver, BC, Canada
Jed Fuhrman, University of Southern California, Los Angeles
Dennis Mangan, University of Southern California School of Dentistry, Los Angeles
Victor Markowitz, Lawrence Berkeley National Laboratory, Berkeley, CA
Randall Murch, Virginia Polytechnic Institute and State University, Blacksburg
Norman R. Pace (NAS), University of Colorado, Boulder
David Relman, Stanford University, Stanford, CA
Edward Rubin, Lawrence Berkeley National Laboratory, Berkeley, CA
George Weinstock, Baylor College of Medicine, Houston, TX
OCR for page R8
The New Science of Metagenomics: Revealing the Secrets of Our Microbial Planet
Although the reviewers listed above have provided constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations, nor did they see the final draft of the report before its release. The review of the report was overseen by John Wooley, University of California, San Diego. Appointed by the National Research Council, he was responsible for making certain that an independent examination of this report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of the report rests entirely with the author committee and the institution.
The committee benefited from briefings provided by severalspeakers. At its second meeting, on May 2, 2006, the committee was briefed by: Michael Gray (by telephone), Professor and Department Head, Canada Research Chair in Genomics and Genome Evolution, Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia, Canada; Mitchell Sogin, Senior Scientist and Director of the Josephine Bay Paul Center for Comparative Molecular Biology and Evolution, The Woods Hole Biological Laboratory, Woods Hole, MA; and Robert Edwards, San Diego State University and Burnham Institute, San Diego, CA. At its third meeting, on July 27, 2006, the committee was briefed by: David J. Lipman, Director, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Rockville, MD; Rolf Apweiler, Head of Sequence Database Group, European Bioinformatics Institute, Cambridge, UK; Victor Markowitz, Head of Lawrence Berkeley National Lab’s Biological Data Management and Technology Center, Berkeley, CA; Paul Gilna, Executive Director, CAMERA, San Diego, CA; and Amaranth Gupta, Associate Research Scientist, Director Advanced Query Processing Lab, San Diego Supercomputer Center, University of California, San Diego.
The committee extends heartfelt thanks to Ann Reid who served as Study Director for this report. The product reflects both Ann’s attention to our charge and her ability to provoke us into addressing it thoroughly. Her outstanding editing contributed greatly to the clarity and logic of the report. We also thank Anne Jurkowski for her dedication to this report and its authors. Throughout the process, the committee relied on Anne’s administrative prowess and her willingness to do whatever was necessary to get the report done or the committee on track. Anne’s aesthetic intuition and visual acuity shaped the report as well as its derivative materials.
We thank Dr. Patrick Schloss for his assistance in building the meta- genomics bibliography and Dr. Luke Moe, Snow Brook Peterson, and Dr. Ainslie Little for helpful discussion and Christina Matta for assuring historical accuracy.
OCR for page R9
The New Science of Metagenomics: Revealing the Secrets of Our Microbial Planet
Contents
SUMMARY
1
1
WHY METAGENOMICS?
12
What Is Metagenomics?,
13
What Microbes Can Do: Four Examples,
15
Microbes Modulate and Maintain the Atmosphere,
15
Microbes Keep Us Healthy,
17
Microbes Support Plant Growth and Suppress Plant Disease,
18
Microbes Clean Up Fuel Leaks,
19
Invisible Communities: Global Impact,
19
Understanding Microbial Communities,
21
The Limits of Pure Culture,
21
The Genomics Promise,
23
Why Genomics Is Not Enough,
25
Most Microbes Cannot Be Cultured,
25
Microbial Diversity and Variation Have No Limits,
27
Metagenomics Offers a Way Forward,
29
Metagenomics Can Contribute to Advances in Many Fields,
31
2
A NEW LIGHT ON BIOLOGY
33
What Is a Genome?,
33
What Is a Species?,
35
What Is the Role of Microbes in Maintaining the Health of Their Hosts?,
37
How Diverse Is Life?,
38
OCR for page R10
The New Science of Metagenomics: Revealing the Secrets of Our Microbial Planet
How Do Microbial Communities Work?,
40
How Do Microbial Communities React to Change?,
43
How Do Microbes Evolve?,
44
What Ecological and Evolutionary Roles Do Viruses Play?,
46
3
FROM GENOMICS TO METAGENOMICS: FIRST STEPS
47
Sequencing Is Just One Kind of Metagenomics,
48
Pioneering Projects in Metagenomics,
50
The Acid Mine Drainage Project,
50
The Sargasso Sea Metagenomic Survey and Community Profiling,
53
The Soil-Resistome Project,
55
The Human-Microbiome Project,
57
Viral Metagenomics,
58
4
DESIGNING A SUCCESSFUL METAGENOMICS PROJECT: BEST PRACTICES AND FUTURE NEEDS
60
Parallels with Traditional Microbial Genome Sequencing,
60
Metagenomics Step by Step,
63
Habitat Selection,
63
Sampling Strategy,
64
Macromolecule Recovery,
65
Getting the Most Out of Metagenomics Studies,
67
16S rRNA-Based Surveys,
67
16S rRNA Phylogenetic and Functional Anchors: A Hybrid Approach,
70
Generation of Large-Scale DNA Sequence,
70
Assembling Whole Genomes,
71
Gene-Centric Analyses,
73
Hybridization- and Array-Based Analyses,
74
Function-Based Analyses of Microbial Communities,
76
Advancing the Field,
77
Sequencing Technology,
77
Gene-Expression Systems,
79
Single-Cell Analyses,
80
Methods for Culturing Uncultured Species,
82
Basic Microbiology,
83
Understanding Microbial Habitats and Collecting Metadata,
83
Downstream Development of Metagenomics,
84
OCR for page R11
The New Science of Metagenomics: Revealing the Secrets of Our Microbial Planet
5
DATA MANAGEMENT AND BIOINFORMATICS CHALLENGES OF METAGENOMICS
85
Genomic Data,
85
Metagenomic Data,
88
The Importance of Metadata,
90
Databases for Metagenomic Data,
92
Software,
94
Analysis of Metagenomic Sequence Data,
95
6
THE INSTITUTIONAL LANDSCAPE FOR METAGENOMICS: NEW SCIENCE, NEW CHALLENGES
98
Major Stakeholders in Metagenomics,
98
The Scientific Community,
98
Funding Agencies,
98
International Coordination,
99
Education and Training,
100
Other Institutional Issues,
102
Data Release,
102
Intellectual Property,
103
Metagenomics and the Convention on Biological Diversity,
104
Biosafety,
105
Outreach,
106
7
A BALANCED PORTFOLIO: MULTI-SCALE PROJECTS IN THE “GLOBAL METAGENOMICS INITIATIVE”
107
The Vision,
107
Characteristics of Successful Large-Scale Projects,
108
Why Metagenomics Needs a “Big Science” Component,
109
What Kind of Large-Scale Projects in the Global Metagenomics Initiative and How Many?,
112
Expected Benefits of Large-Scale Metagenomics Projects,
113
Theory and Principles,
113
Understanding Specific Habitats,
114
Technical Advancement of the Field,
114
International Collaboration and Training,
115
Learning from Previous Large-Scale Genomics Projects,
115
The Human Genome Project,
116
The Arabidopsis Genome Project,
117
Lessons for Metagenomics,
118
OCR for page R12
The New Science of Metagenomics: Revealing the Secrets of Our Microbial Planet
A Preliminary Road Map,
118
Phase I: Choosing Model Communities,
118
Phase II: Planning and Initial Data-Gathering,
120
Phase III: Implementation,
122
Conclusion,
122
8
RECOMMENDATIONS
124
9
EPILOGUE
134
REFERENCES
144
APPENDIXES
A
Statement of Task
151
B
Committee Biographies
152
