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.

Nimravid posted a summary, which was graciously acknowledged today by Dr. Gregory, and that was how I learned about the paper. Nimravid’s summary is good (as are all of Nimravid’s posts), but I recommend reading the entire paper, which is very readable and well-presented. I found that I have a pretty clear idea of how to interpret evolutionary trees, but I learned the differences in the terms dendrogram, cladogram, and phylogram.

Dr. Gregory makes an important point in his paper:

[I]t is impossible to know with certainty that any given phylogeny is historically accurate. As a result, any reconstructed phylogenetic tree is a hypothesis about relationships and patterns of branching and thus is subject to further testing and revision with the analysis of additional data.

In my mind, this is why evolution is a science. An evolutionary tree is a model of the evolutionary relationships among organisms. A good model is consistent with existing observations, and it provides a hypothesis than can be tested as additional data are gathered. If the model is inconsistent with the new data, the model is revised and subjected to testing with even more data.

The premise is simple. The site presents a word and four possible meanings, and you click on the meaning you think is correct. With each correct guess, you earn 20 grains of rice that the site owner donates to the United Nations World Food Program. Advertisers pay to display ads on the site, so they are the ones who ultimately pay for the donated rice. The game is fun and addictive, and it has the benefit that you can learn some new words.

As a scientist, I have a pretty large vocabulary, so I can reach a vocabulary score of 48. My wife, who edits medical textbooks and consequently has an enormous vocabulary, routinely reaches 53. A score of 55 is the highest possible.

I have learned some new words, some useful and some not. When someone mentions they wore a rebato trimmed with vair, now I know what they’re talking about.

But one of the words hit my hot button. The word was nostoc, and the required answer was blue-green alga. This annoys me because it is like calling a dolphin a fish, a mushroom a plant, or water an element. The answer is incorrect.

What were once called blue-green algae are properly called cyanobacteria. The distinction is important, because cyanobacteria are prokaryotic organisms and algae are eukaryotic organisms.

While I’m ranting: It’s one alga, many algae; one bacterium, many bacteria.

On 13 March 2007, Bosco Ho wrote a post entitled “Notes to a Young Computational Biologist” on his Trapped in the USA blog. I don’t remember how I happened to come across this post the first time, because I wasn’t reading blogs systematically then, but something about this topic clicked in me, and on 25 March I posted a long comment about some things I thought Dr. Ho had omitted.

Time passed, and in October or November, I received an email from a recruiter who wanted to interest me in a bioinformatics or programming job on the West Coast. I couldn’t figure out where she had heard of me, except that she mentioned in the email that she had seen my name on the boscoh.com web site. This mystified me, because I had forgotten all about the events in March. I did a little poking around on the web site, but I couldn’t find my own name. So I concluded that she was completely mistaken—that she actually wanted to recruit Bosco Ho but had sent me the email in error—and I decided not to respond.

The benefit of this apparent error was that I learned (for what I thought was the first time) about Dr. Ho’s site, which is full of great writing and useful information. I now work with quite a few scientists who are experts at protein structure, but this is a new field for me because I was trained as a DNA jockey (you know—molecular biology, cloning, sequencing, and all that). Trapped in the USA provided me with additional background reading on protein structure.

At the beginning of this year, I decided it was time to start another web site, so I registered sphaerula.com. One of the things my hosting provider offers is an installation of WordPress, and that’s how I got started blogging. Since mid-February, I have been immersed in reading biology and bioinformatics blogs and writing posts of my own. I’ve discovered many wonderful blogs, and I discovered Trapped in the USA for the third time.

On weekends, I have been methodically reading blogs from beginning to end. (This is going to take me a long time as I follow the branches from the blogrolls.) When I began reading Trapped in the USA, I rediscovered Dr. Ho’s “Notes to a Young Computational Biologist” post, and I rediscovered my comments.

So in the course of a little more than 11 months, I’ve made a discovery, a rediscovery, and a rerediscovery. The difference is that now I am fully engaged in blogging and in reading blogs, and this time the discovery will stick with me. I know now that Dr. Ho is a widely respected blogger in the bioinformatics blogging community, and I won’t forget it this time.

By the way, if you happen to be that recruiter, I apologize for not responding. I love the West Coast, having grown up in Oregon and earned my Ph.D. at Berkeley. But I have a good job, I love Boston, and I’m not inclined to move. But I’m happy to recommend a talented computational biologist who is named Bosco Ho.

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.”

In May, 2007, Jonathan provoked a long and fascinating discussion of a paper by Liu and Ochman on the formation of the flagellar system. The consensus was that the paper was irretrievably flawed because of the incorrect use of and incorrect interpretation of BLAST results.

However, Jonathan made a surprising point that many disagreed with.

Personally, I’ve never been convinced that protein structure is of much use in inferring homology or the lack of it; systematists have been burned so many times by incorrectly assumed (non)homology of gross morphological traits in light of convergent and divergent evolution; why should morphology at the protein level be any different? The beauty of molecular systematics is that it’s freed us from having to deal with morphology at all.

Others in the discussion argued forcefully and convincingly that folds are more highly conserved than sequence, and that similar folds provide strong evidence for homology (descent from a common ancestor). I learned a lot from this discussion that will be useful to me.

As I continued my reading, I discovered from Jonathan’s publications page that Jonathan was a coauther on the paper describing the genome sequence of Synechococcus CC9311. The first author was Brian Palenik, a friend of mine who was doing his postdoc in Bob Haselkorn’s lab at the same time I was doing mine. Brian is a much better scientist than I am and deserves his success.

Jonathan’s review of J. Craig Venter’s book, A Life Decoded: My Genome: My Life, piqued my interest, so now I will have to track down a copy.

This was time well spent for me, and I derived great enjoyment in reading Jonathan’s blog. Jonathan hasn’t posted since December, 2007; I am looking forward to new contributions.

The idea is that plant viruses are poorly understood but play important roles in nature. In the 26 January 2007 issue of Science, Dr. Roossinck and colleagues published a paper in which they described a virus that conferred the ability of a fungus and a tropical grass, in a three-way mutualistic association, to grow at high soil temperatures. When the fungus was cured of the virus, it could no longer confer heat tolerance to the grass.

The viruses that are the most well-characterized are those that cause disease in humans or plants, but Dr. Roossinck estimates that only 1% of all viruses cause disease. In previous surveys of viral genomes, most of the genes identified were completely novel, with no hits in GenBank. Hence, Dr. Roossinck believes that viral genome sequences will provide a rich source of new proteins with unknown functions.

The project is focusing initially on plants that are related to major crop species. The researchers take plant samples back to lab, isolate total nucleic acid, treat with DNase, and look for double-stranded RNA, the hallmark of 80% of plant viruses. This approach is taken because double-stranded RNA in plants is rare except for that produced by viruses. On average, about 60% of the samples yield viral dsRNA. The dsRNA is amplified to DNA by PCR using random hexamer primers and reverse transcriptase. The resulting samples are contaminated with ribosomal genes and other plant genes, but the group has succeeded in obtaining a lot of viral sequences. The group is currently working on obtaining sequence and analyzing the data.

Dr. Roossinck spoke about this project in 2007 at the Center for Biodiversity and Conservation’s Twelfth Annual Symposium at the American Museum of Natural History. The topic of the symposium was Small Matters: Microbes and their Role in Conservation.

Microbe World Radio is sponsored by the American Society for Microbiology, of which I am a member. The shows are produced by Finger Lake Productions. Daily podcasts are available through iTunes and other podcast providers. Archives of Microbe World Radio shows can be found here and here.

Video and audio presentations from the Center for Biodiversity and Conservation’s Twelfth Annual Symposium are available here.

Much of the the 7 December 2007 issue of Science is devoted to the Hinode (“sunrise”) solar space telescope mission. (The web site for the mission is in Japanese, if you read that language.) Hinode was launched in September 2006 and since October 2006 has observed the sun from earth orbit. The initial observations have provide clues for solving the mystery of heating the sun’s corona.

In a perspective, Erdélyi and Fedun (p. 1572) explain that there are at least three fundamental questions to be answered.

Where is the energy generated? How does the generated energy propagate from the energy reservoir to the solar corona? How does the transported energy dissipate efficiently in the solar corona to maintain its multimillion-kelvin temperature?

It is now clear that the powerful magnetic fields in the solar atmosphere play a crucial role in heating the corona. In 1970, Hannes Alfvén was awarded the Nobel prize in physics for his predictions of magnetic waves, now called Alfvén waves, in the solar atmosphere. Many of Hindode’s observations are consistent with the presence of Alfvén waves, and the waves are sufficiently powerful to generate the solar wind and heat the corona.

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.

Both the paper and the article make special note of the role of amateur astronomers in making regular planetary observations. Amateur astronomers around the world can coordinate to make series of continuous observations of a planet over many weeks. The advancement of optical and image processing technologies has led to astonishing improvements in the quality of the images that can be obtained with relatively modest equipment. Dr. Sayanagi writes:

This coverage from around the world nicely complements the more powerful, but less flexible capabilities of the large ground- and space-based telescopes.

For example, see the website of Chrisopher Go, who is one of the contributing authors to the paper. Mr. Go has a second website devoted to Jupiter’s Red Spot Junior.

There is evidence that RNA polymerase II replicates hepatitis delta virus, which has an RNA genome, but this replication is slow in vitro. The authors speculate that unidentified factors present in the cell increase the processivity of RNA polymerase II when it uses an RNA template.

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.

In solid phase synthesis, the first residue is covalently attached to the solid phase, a polymer. Additional residues are added one at a time in a reaction that can exceed 99.5% efficiency, after which the unreacted starting material is washed away, with the product retained on the solid phase. Once the synthesis is completed, the protein is removed from the polymer. This method enabled the development of automated peptide synthesizers.