The New Science of Metagenomics Revealing the Secrets of Our Microbial Planet (2007) / Chapter Skim
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3 From Genomics to Metagenomics: First Steps
3 From Genomics to Metagenomics: First Steps
Pages 47-59
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From page 47... ...
And this is true not only for humans: it is now nearly unthinkable to launch a major comprehensive initiative in the biology of any species without sequencing its genome. We have genome sequences for many species of fungi; for nematodes, fruit flies and zebrafish (all highly useful models for human biology)
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From page 48... ...
. For environments of low complexity, such as the acid mine drainage described below, it is possible to assemble several genomes simultaneously from an environmental sequence database by using various sophisticated "binning" methods (see Box 3-1)
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From page 49... ...
population, and metabolic processes that affect methane generation in the permafrost as it experiences global warming -- is in principle not different from monitoring such changes in a culture of saccharomycetes as it adapts to a new substrate, in a fruit fly embryo as it develops, or in a human tumor as it progresses. Structural genomics -- the systematic expression and structural characterization of the products of all the uncharacterized genes in a genome -- will also be a boon; so far, this approach has been applied in the organismal context, but all the highly expressed but unidentified genes in a community metagenome would be an ideal target.
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From page 50... ...
Five types of projects are discussed: a simple community analyzed in depth, a large-scale sequencing survey in an environmental setting, a functional genomic project, a project focused on a microbial community living in a host, and a project focused on viruses. The Acid Mine Drainage Project Microbes in collaboration with humans have wreaked havoc on some geologic sites.
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From page 51... ...
FROM GENOMICS TO METAGENOMICS FIGURE 3-1 An acid mine drainage site. From such a location, metagenomics studies have allowed assembly sequences of a consortium of genome sequences and 3-1.eps fostered pioneering studies of gene exchange and expression.
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From page 52... ...
Therefore, many of the challenges and opportunities of microbialcommunity genomics cannot be fully appreciated from this single, exceptionally simple example. Further exploration of diverse microbial communities now demonstrates that shotgun sequencing alone cannot easily be used to complete whole microbial genomes, even in communities that are only moderately complex.
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From page 53... ...
In retrospect, that is perhaps not too surprising in that it is widely recognized that native microbial populations harbor vast amounts of sequence variation. Inherent intrapopulation genetic complexity, combined with variable species richness and evenness, still poses extreme challenges for standard shotgun sequencing and assembly approaches developed for single microbial strains.
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From page 54... ...
Careful sampling and verification procedures, coordination with field experts, and independent sample validation are prerequisites for largescale metagenomic sequencing efforts. Deep knowledge of the environment sampled, experience with the types and distributions of the indigenous microbes, and independent sample validation methods, will facilitate scientifically rigorous metagenomic studies.
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From page 55... ...
In lieu of full genome assemblies, comparative analyses of the Sargasso Sea and other datasets have demonstrated the utility of individual gene comparisons within and between samples. A new approach in microbial ecology, comparative community genomics, is emerging from such studies.
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From page 56... ...
The resistome study revealed aminoglycoside resistance genes that encode a group of enzymes called acetyltransferases that are more closely related to each other than any previously described members of the family (Riesenfeld et al.
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From page 57... ...
, infectious diarrhea, and various immunopathologic states, including inflammatory bowel diseases. Initial results of 16S rRNA gene-based enumerations of the microbial communities of a small number of humans have revealed remarkable diversity in a number of habitats, including the gut (Eckburg et al.
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From page 58... ...
Analysis of 78 million base pairs of unique DNA sequence disclosed that, compared with the human genome and previously sequenced microbial genomes, the gut metagenome is enriched in genes involved in the breakdown and fermentation of otherwise indigestible plant-derived polysaccharides that form an important part of modern diets, the detoxification of xenobiotics consumed intentionally or inadvertently, and the synthesis of essential amino acids and vitamins. These findings emphasize that the human metabolome is actually a composite of human and microbial attributes; they also point to a future in which it may be possible to optimize the nutritional status of the overfed or underfed on the basis of knowledge of their gut microbial ecology, or to predict the bioavailability of orally administered drugs, or to forecast the susceptibilities of individuals or populations to particular types of cancer.
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From page 59... ...
The double-stranded viral DNA sequences identified in sediments suggested an important role for temperate phages, for example, viruses that can integrate into their host's genome. A large comparative analysis of seawater viral assemblages collected from diverse locales recently indicated that marine viral species have a global distribution (Angly et al.
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