(Right: Ham and Clyde as they are affectionately known to colleagues.) Lead researcher  Clyde Hutchison (right), said “To me, the most remarkable thing about our synthetic cell is that its genome was designed in the computer and brought to life through chemical synthesis, without using any pieces of natural DNA”.

His colleague, Hamilton Smith, (left) added “With this first synthetic bacterial cell and the new tools and technologies we developed to successfully complete this project, we now have the means to dissect the genetic instruction set of a bacterial cell to see and understand how it really works”.

The resultant furore has all but obscured the Institute's other research announcement of the Human Microbiome Jumpstart Reference Strains Consortium which now has a catalog of 178 microbial reference genomes isolated from the human body.

The human body is teeming with a variety of microbial species. This collective community is called the human microbiome. The role these microbes play in human health and disease is still relatively unknown but likely very important.

The NIH Human Microbiome Project launched in 2007, as part of the National Institutes of Health’s (NIH) Common Fund’s Roadmap for Medical Research is a $157m, five-year effort that will implement a series of increasingly complicated studies that reveal the interactive role of the microbiome in human health.

The HMP Jumpstart Consortium  has been charged with selecting microbial strains to sequence from: gastrointestinal tract, oral cavity, urogenital/vaginal tract, skin and respiratory tract;  creating standards for sequencing and annotation; and ensuring rapid release of information to the scientific community. 
 
The Consortium’s goal is to ultimately produce 900 reference genomes. So far the group has produced and released into the public domain 239 genomes. The 178 genomes represented in this publication are completely annotated and analyzed.

Sequencing was conducted using mostly the Roche-454 sequencing platform along with some traditional Sanger sequencing.  The team compared the sequenced reference genomes to human metagenomic data in the public domain to find new genes and proteins, to ascertain some function for these genes and to assign metagenomic data to species.

From the analysis of 547,968 predicted proteins, the team found 29,987 unique proteins. This data set was compared to a randomly selected data set of 178 previously sequenced prokaryotic genomes found in the public database GenBank and there were fewer unique genes in this data set than in the human microbiome. This is a unique finding and suggests that there is greater microbial diversity in the human microbiome than was previously known.

The group found some novel gene functions unique to particular microbial strains in the reference genome set. While the group cautioned that this was preliminary data and more work was needed on gene functions, some initial insights into important functions were gleaned.

For example, they found certain proteins and specific virulence factors associated with gastric ulceration, regulation proteins associated with the development of phage (viruses that infect bacteria), and some enzymes involved in the metabolism of sugars and amino acids.

One of the main goals of having HMP reference genomes is to help interpret and understand metagenomic data. Since the HMP reference genomes were isolated from humans and were not in metagenomic data sets, the group was uncertain if these reference genomes would aid in identifying metagenomic sequences.

However, in comparing 16.8m sequences, the team found that 62 of the HMP reference genomes recruited 11.3m sequences, and of these, 6.9m sequences recruited most closely to the HMP reference genomes. Thus, having the HMP reference genomes allowed for 20 to 40% of metagenomic sequences to be identified.

This analysis shows that the HMP reference genomes are aiding substantially in the understanding of the human microbiome but the group added that there is much work to be done in fully understanding the microbiome, and achieving the goal of 900 sequenced reference genomes is necessary for a more complete understanding.

The group concludes that while this initial catalog focused on bacteria, future efforts will concentrate on adding eukaryotic microbes and viruses since these are both found in the human microbiome.The group will continue its work in developing standards for sequencing unculturable strains, strain selection criteria, and providing online access to these large datasets, among many issues.

Corresponding author (right) JCVI’s Karen E. Nelson, PhD,  said, “This is a major study that moves us in the right direction to understanding the complex microbiota associated with the human body, and outlines how we benefit from this relationship.  We will continue to learn more about the impact of these species in health and disease conditions.”
 
Nelson also added that the consortium anticipates several additional significant publications on the human microbiome in the near future.