Research abstract
Letter abstract
Nature Biotechnology 26, 1029 - 1034 (2008)
Published online: 17 August 2008 | doi:10.1038/nbt.1488
High-resolution metagenomics targets specific functional types in complex microbial communities
Marina G Kalyuzhnaya1, Alla Lapidus3, Natalia Ivanova3, Alex C Copeland3, Alice C McHardy4,8, Ernest Szeto5, Asaf Salamov3, Igor V Grigoriev3, Dominic Suciu6, Samuel R Levine2, Victor M Markowitz5, Isidore Rigoutsos4, Susannah G Tringe3, David C Bruce7, Paul M Richardson3, Mary E Lidstrom1,2 & Ludmila Chistoserdova2
Most microbes in the biosphere remain unculturable1. Whole genome shotgun (WGS) sequencing of environmental DNA (metagenomics) can be used to study the genetic and metabolic properties of natural microbial communities2, 3, 4. However, in communities of high complexity, metagenomics fails to link specific microbes to specific ecological functions. To overcome this limitation, we developed a method to target microbial subpopulations by labeling DNA through stable isotope probing (SIP), followed by WGS sequencing. Metagenome analysis of microbes from Lake Washington in Seattle that oxidize single-carbon (C1) compounds shows specific sequence enrichments in response to different C1 substrates, revealing the ecological roles of individual phylotypes. We also demonstrate the utility of our approach by extracting a nearly complete genome of a novel methylotroph, Methylotenera mobilis, reconstructing its metabolism and conducting genome-wide analyses. This high-resolution, targeted metagenomics approach may be applicable to a wide variety of ecosystems.
- Department of Microbiology, University of Washington, Benjamin Hall IRB, 616 NE Northlake Place, Seattle, Washington 98105, USA.
- Department of Chemical Engineering, University of Washington, Benjamin Hall IRB, 616 NE Northlake Place, Seattle, Washington 98105, USA.
- Production Genomics Facility, DOE Joint Genome Institute, 2800 Mitchell Drive, Bldg. 400, Walnut Creek, California 94596, USA.
- Bioinformatics and Pattern Discovery Group, IBM Thomas J. Watson Research Center, 1101 Kitchawan Road, Yorktown Heights, New York 10598, USA.
- Biological Data Management and Technology Center, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Mail Stop 50A-1148, Berkeley, California 94720, USA.
- Combimatrix Corporation, 6500 Harbour Heights Pkwy., Mukilteo, Washington 98275, USA.
- DOE Joint Genome Institute, Los Alamos National Laboratory, PO Box 1663, Los Alamos, New Mexico 87545, USA.
- Present address: Computational Genomics and Epidemiology Group, Max Planck Institute for Computer Science, Campus E1 4, 66123 Saarbruecken, Germany.
Correspondence to: Ludmila Chistoserdova2 e-mail: milachis@u.washington.edu
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