Fungi and plants enter a symbiotic relationship in which the microrrhizae of fungi join with the roots of plants, allowing an exchange of nutrients between the organisms. Plants transfer simple carbohydrates, the products of photosynthesis, to the fungi, and they receive in return water and minerals, including ammonia and phosphate ions.

The researchers identified approximately 21,000 genes in the 65 million base pair genome; about 70% of the predicted genes have significant similarity to genes in the sequence databases. As might be expected, the number of predicted membrane-bound transporter proteins is large.

The authors of the paper and Dr. Cullen in his commentary noted that it was expected that the L. bicolor genome would contain genes encoding enzymes for breaking down cellulose and lignin. It was surprising, therefore, that only one gene encoding an endoglucanase with a cellulose-binding domain was identified, and no genes encoding enzymes for breaking down cellulose were found. In contrast, a large number of genes predicted to encode lipases and proteinases were identified, suggesting that L. bicolor derives nutrients from the degradation of bacteria and invertebrates. Martin et al. write:

These observations suggest that the inventory of L. bicolor plant cell wall-degrading enzymes underwent massive gene loss as a result of its adaptation to a symbiotic lifestyle, and that this species is now unable to use many plant cell wall polysaccharides as a carbon source, including those found in soil and leaf litter.

Having now in hand this fungal genome and the genome of the black cottonwood, Populus trichocarpa, which enters into ectomycorrhizal symbiosis, the authors predict it will be much easier to identify the genes that mediate the symbiotic relationship.

The first is Gene Sherpas, a blog by Steve Murphy, M.D., about “personalized medicine and you.”

To usher in the new paradigm of personalized medicine we will need to travel a perilous path. Much like the route through the Himalayas it has punished the naive and self-reliant. That is why I have dedicated my life to being a Gene Sherpa. What is a gene sherpa? The Sherpa speaks the language of the trail, he/she knows short cuts and dangerous paths to avoid. This blog is for those wishing to take the journey and those wishing to become Gene Sherpas. Interested? Email me…

Dr. Murphy also writes:

I am the founder of a Personalized Medicine practice (likely the first private practice of its kind). In addition I am the Clinical Genetics Fellow at Yale University until 2010. Now not under contract and that’s why I am posting and running my practice. I also am developing a modern medical genetics curriculum for residents and other physicians. On this blog I am educating the public and hopefully some physicians about the field of genetics and personalized medicine.

The Gene Sherpas blog contains many informative and provocative posts, including a recent post about twin studies and how identical twins aren’t actually so identical when DNA methylation and copy number variation are taken into account.

From Gene Sherpas, I learned about Misha Angrist’s GenomeBoy blog. Dr. Angrist earned a Ph.D. in Genetics at Case Western Reserve University, and he now writes about personal genomics. Dr. Angrist writes:

I work as the Science Editor for the Duke University Institute for Genome Sciences & Policy (although this site and its content are my own). In 2007 I became the fourth subject in Harvard geneticist George Church’s Personal Genome Project. As the PGP moves forward, I am chronicling the dawn of personal genomics, that is, people obtaining their genomic information for whatever reason(s) and figuring out what to do with it. I am interested in the relevant technologies and especially the attendant privacy and other ethical/legal/social issues.

Dr. Angrist posts frequently about his participation in the Personal Genome Project and about the rapid technological advances that will make personal genomes easy to obtain in the near future.

The paper was originally published online on 24 January 2008, at which time there was a lot of coverage in the press and in blogs. For example, see “Synthetic Genome: Signed, Sealed, Decoded”, by Andrew Pollack of the New York Times, and a roundup of coverage of the announcement at blog.bioethics.net. This paper was also the topic of Science Friday on 25 January 2008.

While the assembly of this synthetic genome is without a doubt a significant technical achievement, the paper does not reveal whether the genome can be transplanted into a bacterial cell. This makes the result anticlimactic; it was like reading about the building of a new airplane, with lots of description about the design of the wings and how the rivets had to be placed just so, but without a demonstration that the airplane could actually fly. I suspect strongly that the transplantation was attempted (several times) without success.

The same group has shown that it is indeed possible to transplant a genome from one bacterial species to another, as described in a paper in Science by Lartigue et al. We must now wait for the JCVI to get their airplane off the ground.

University of California—Davis Professor Jonathan A. Eisen, on his The Tree of Life blog, jokingly complained that Ms. Harmon had interviewed him but had discarded his quotes. Ms. Harmon, good sport that she is, responded in the comments by contributing outtakes of the article that included discarded quotes from Dr. Eisen and from J. Craig Venter.

Dr. Venter, of course, has already had his genome sequenced and analyzed by his institute, the J. Craig Venter Institute in Rockville, Maryland. The paper describing Dr. Venter’s genome was published in PLoS Biology. Dr. Venter has written a book, A Life Decoded: My Genome: My Life, and a good review is available on Dr. Jonathan Badger’s T. taxus blog.

Dr. James Watson, one of the co-discoverers of the structure of DNA, has had his genome sequenced; the data are available at the James Watson’s Personal Genome Sequence Browser web site at Cold Spring Harbor Laboratory.

Dr. Church has also organized the Personal Genome Project. This project will sequence and analyze the genomes of volunteers, who will share their medical records, making the data much more useful. I wrote eight days ago about the 1000 Genomes Project, for which medical records will not be available. A blog about the Personal Genome Project, named The Personal Genome, is written by Jason Bobe.

Another company that is providing personal genome data is 23andMe, which provides a blog named The Spittoon. For about $1000, 23andMe obtains data on nearly 600,000 single nucleotide polymorphisms (SNPs) and provides a genetic analysis of the data. Andrew Scheidecker had his genome analyzed by 23andMe in December, 2007, and wrote software called Personal Genome Explorer that made his data available to everyone.

The goal of inexpensively obtaining a genome analysis was deemed important enough for the Archon X Prize for Genomics to promise an award of $10 million for the successful sequencing of 100 genomes in 10 days at a cost of less than $10,000 per genome. See “$10 Million Prize Set Up for Speedy DNA Decoding”, by Nicholas Wade of The New York Times.

Other companies that have developed high-throughput sequencing technologies that might make the relatively inexpensive genome within reach are 454 Life Sciences, Helicos BioSciences, and Pacific Biosciences. Dr. Eisen saw a talk about the Pacific Biosciences technology and came away enthusiastic, writing in his blog:

But it was the last talk of the whole meeting that really did blow my mind. It was from Steve Turner from Pacific Biosciences. He presented an overview of their sequencing technology as well as a tiny bit of data. Now, normally I am uninterested in marketing talks where little data is presented. But this talk was different. First, their technology clearly has enormous potential for revolutionizing the sequencing field. Basically, what they are doing is reading the activity of a DNA polymerase as it replicates a single DNA molecule and they do it in real time. He referred to this as using the DNA polymerase as a sequencing engine and then he took the crowd through the details of the technology and some of the modifications they have made to make it work better.

Ms. Harmon’s article is one of a series in the New York Times named The DNA Age; another good article written by Ms. Harmon is My Genome, Myself: Seeking Clues in DNA. Other good articles at the New York Times on personal genomes and high throughput sequence are “The Race to Read Genomes on a Shoestring, Relatively Speaking” and “Working by Eavesdropping on DNA Doing Its Work”, both by Andrew Pollack.

In a few years, it will be routine for everyone to have their genome sequenced and analyzed. It will take a long time to get the quality of the predictions up to a useful level, however. How much of the genome needs to be sequenced to obtain an accurate analysis, 600,000 SNPs (23andMe) or the full genome (Knome, Personal Genome Project)? I personally am interested in having my genome analyzed because, as a scientist, I am always interested in data. However, I would consider the genetic analysis to be speculative until many more genomes have been analyzed.

Notes added on 6 March 2008:

The Genetic Future blog has a post from 22 January 2008 about negative reaction to 23andMe.

I learned from GenomeWeb today that on 8 February 2008, Helicos BioSciences announced that it had sold its first sequencer. Yesterday, Expression Analysis confirmed that they were the purchaser. Expression Analysis said they will use the sequencer for “de novo sequencing, candidate gene sequencing, and digital gene expression.”

Li et al. examined 642,690 single-nucleotide polymorphisms in the autosomes of 938 individuals representing 51 populations from all over the world. Their analysis was based on the proposition that each person’s genome originated from K different ancestral populations. They performed the analysis with K = 2 through K = 7. With K = 7, they found that the seven components corresponded to populations from Africa, Middle East, Europe, Central/South Asia, East Asia, Oceania, and the Americas. Individuals from the Middle East displayed the most mixed ancestry; Palestinians, for example, displayed ancestry from South/Central Asia, Europe, and the Middle East.

The researchers created a maximum likelihood phylogenetic tree from the 51 populations. The sub-Saharan African populations appeared nearest the root of the tree, which was established by the chimpanzee branch, consistent with the hypothesis that humans first appeared in Africa and then migrated to the other continents. The two most distant branches of the tree represented the populations from Oceania and from the Americas.

The large number of markers allowed the group to distinguish finer differences among the populations. For example, the eight European populations sampled in the study — Adygei (an ethnic group from the Russian Caucasus), Basque, French, Italian, Orcadian, Russian, Sardinian, and Tuscan — were well separated in a principal component plot.

The press release details the goals of the project, which are to:

• develop a new, highly detailed map of variation in the human genome, a resource that should enable the association of variation of single nucleotide polymorphisms with diseases
• use new DNA sequencing technologies to reduce the cost of the sequencing effort to only $30-50 million

However, no medical information will be available for the persons whose genomes will be sequenced. This seems to negate the value of a lot of the data, since there will be no way to identify associations of SNPs with specific genetic disorders.

The first phase of the project will involve three pilot studies. In the first pilot study, the project will obtain the sequences of six genomes at 20x coverage from two families using new sequencing technologies. This will provide working experience with the new technologies and will enable the project to choose which sequencing method to move forward with.

In the second pilot study, the project will obtain 2x coverage of 180 genomes to provide experience with data management and interpretation.

The third pilot study will focus on obtaining the sequences of the exons of approximately 1000 genes from 1000 people. This study will provide additional experience in data management and interpretation.

The project will then move on to the production phase, which will take two years. The project leaders anticipate a sequencing throughput of more than 8 billion bases per day. It will be extremely challenging to capture and analyze so much data.