Archive for the 'Biology' Category
I spent this morning reading Jonathan Badger’s T. taxus blog (“Reflections on science, literature, and history by an American Badger”) and web site. Jonathan is a microbial genomicist at the J. Craig Venter Institute (JCVI) in La Jolla, California. Taxidea taxus is the systematic name for the American badger.
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.
March 02 2008 | Biology | Comments Off
On 25 February 2008, Microbe World Radio reported on the 5000 virus genome project, a research project initiated by Professor Marilyn J. Roossinck at the Samuel Roberts Noble Foundation in Ardmore, Oklahoma. Dr. Roossinck’s objective is to use the high-throughput technology from 454 Life Sciences to obtain the sequences of the genomes of 5000 different plant viruses isolated from plants in Costa Rica.
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.
March 01 2008 | Biology | Comments Off
Separate analyses of genetic markers from the mitochondrial genome, the Y chromosome, and autosomes have revealed that all humans are descended from a small group of ancestors that lived in eastern Africa. In the 22 February 2008 issue of Science, Li et al., in a paper titled “Worldwide human relationships inferred from genome-wide patterns of variation”, have taken this analysis to a much more detailed level.
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.
February 28 2008 | Biology | Comments Off
In a paper in the 15 November 2007 issue of Nature, Lehmann et al. explore in detail the RNA-dependent activity of RNA polymerase II from Saccharomyces cerevisiae. RNA polymerase normally transcribes RNA from a DNA template, but the ability of RNA polymerase to use an RNA template suggests that RNA polymerase could have evolved from an enzyme that replicated viral RNA genomes. It is hypothesized that, during the transition from the RNA world to our DNA-based world, this ancient replication enzyme evolved to use DNA as a template.
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.
February 26 2008 | Biology | Comments Off
On January 22, 2008, an international consortium of genome sequencing centers announced the 1000 Genomes Project. The goal of the project is to obtain the sequences of 1000 human genomes. Currently, sequences of three human genomes are publicly available.
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.
February 25 2008 | Biology | Comments Off
Bruce Merrifield, who won the Albert Lasker Award for Basic Medical Research in 1969 and the Nobel Prize in Chemistry in 1984, died on May 14, 2006, at the age of 84. Professor Merrifield, working at the Rockefeller Institute for Medical Research (now Rockefeller University), invented solid phase protein synthesis. This work enabled the efficient synthesis of proteins up to 100 residues in length, and the technology was later adapted to the synthesis of oligonucleotides.
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.
May 22 2006 | Biology | Comments Off
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