Published online 20 May 2010 | Nature | doi:10.1038/news.2010.254

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Colonizers give up sequence secrets

First results from human microbiome project yield nearly 30,000 new genes.

Click for a larger version of this image.AAAS/Science

The US Human Microbiome Project has sequenced the genomes of 178 members of the community of microbes that calls the human body home.

The project — a US$157-million, five-year endeavour funded by the US National Institutes of Health — aims to characterize the many microorganisms that live in and on the human body, such as in our guts, mouths and on our skin, in the hope of learning how this largely harmless community contributes to everything from digestion to disease. Researchers want to determine whether there is a core collection of microbes — including bacteria, viruses and fungi — that is shared by everyone, and how changes in this 'microbiome' may affect health. They also want to sequence 900 of the microbes to serve as reference strains, to help researchers to understand the evolutionary relationships within the microbiome.

In a paper published this week in Science1, the Human Microbiome Jumpstart Reference Strains Consortium reveals its analysis of the first 178 completely annotated genome sequences from the human microbiome. Another 178 have been sequenced to some extent, but not yet completed. The team identified almost 30,000 new microbial genes, highlighting the fact that we still have much to learn about the genetics of microorganisms.

Earlier this year, preliminary results2 released by a European consortium called Metagenomics of the Human Intestinal Tract, or MetaHIT, produced a catalogue of 3.3 million microbial genes that are present in about 1,000 species of bacteria (see 'Gut bacteria gene complement dwarfs human genome'). In addition to this catalogue of genes, which was not sorted into distinct genomes, MetaHIT aims to sequence 100 genomes from the microbiome. This, together with the US project, will eventually bring the total number of sequenced microbiome genomes to more than 1,000.

Even so, that will still only scratch the surface of the microbiome's complexity, says Karen Nelson, a microbiologist and director of the J. Craig Venter Institute in Rockville, Maryland, and an author on the latest study1.

Genetic diversity

Nelson and her colleagues sequenced strains that had been isolated from the skin, nose and mouth, gut, blood, genitals and urinary tract of volunteers, and then grown in cultures in the lab.

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The need for lab culturing immediately limits the variety of microbes that can be sequenced, because many human-dwelling microorganisms do not survive when removed from their habitat. Researchers eventually hope to sequence the microbes that cannot be cultured using single-cell sequencing technologies that are currently under development, says Nelson.

In the meantime, even the preliminary results of the analysis are enough to highlight the diversity of the human microbiome, says David Relman, a microbiologist at Stanford University School of Medicine in Palo Alto, California. The collection of 1,300 complete bacterial genomes that are already sequenced and deposited into public databases is biased towards disease-causing microbes, he notes, so comparatively little is known about our more peaceful colonizers.

"The sheer number of unique genes is impressive," he says. "They show how much novel genetic and potentially functional diversity is still buried in the human microbiome." 

  • References

    1. The Human Microbiome Jumpstart Reference Strains Consortium. Science 328, 994-999 (2010). | Article | ChemPort |
    2. Qin, J. et al. Nature 464, 59-65 (2010). | Article | ChemPort |
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