Stable-isotope probing of DNA: insights into the function of uncultivated microorganisms from isotopically labeled metagenomes.

Stable-isotope probing (SIP) of environmental genomic DNA allows populations in a natural microbial community to be identified through the incorporation of (13)C- or (15)N-labeled substrates into biomass. The isotopically labeled DNA is retrieved by density gradient centrifugation, and active microorganisms identified by molecular analysis of the DNA. Recent advances have set the stage for DNA-based SIP with higher sensitivities, shorter incubation times, and more relevant substrate concentrations than used previously. The first demonstration of a DNA-SIP-based metagenome analysis has paved the way for hypothesis-driven studies in environmental genomics.