Monday, January 28, 2008
But I was digging through some old papers and found this ... a paper I wrote in ninth grade. We got to select a topic for the paper and mine ... "Describe one step in the evolution of a bacterium." The funny thing is --- I do not remember this at all. I mean, I remember reading books by Gould that got me interested in evolution. But surely Gould did not write a lot about bacterial evolution. Where did I come up with this topic? I haven't a clue. Anyway - here is the essay - errors, fluffy handwriting, and all.
Wednesday, January 23, 2008
He had me at the beginning ... and as usual has very clear discussions of the steps needed for life to have originated:
If complex cycles analogous to metabolic cycles could have operated on the primitive Earth, before the appearance of enzymes or other informational polymers, many of the obstacles to the construction of a plausible scenario for the origin of life would disappear. If, for example, a complex system of nonenzymatic cycles could have made nucleotides available for RNA synthesis, many of the problems of prebiotic chemistry would become irrelevant. Perhaps a simpler polymer preceded RNA as the genetic material—for example, a polymer based on a glycerol-phosphate backbone  or a phosphoglyceric acid backbone. Could a nonenzymatic “metabolic cycle” have made such compounds available in sufficient purity to facilitate the appearance of a replicating informational polymer?The paper then discusses details of various metabolic cycles and why the current evidence is not completely convincing in terms of the exact path that was taken in the origin of life. Note to ID supporters - this does not friggin' mean that he is saying life could not have originated from non living systems. He is simply pointing out that our understanding of it is incomplete. As, by the way, is our understanding of how blood works. But that does not stop us from thinking that blood does in fact, well, work.
Anyway, once you get over the fact that some ID supporters will misuse his work, the end is a great call for what needs to be done:
The prebiotic syntheses that have been investigated experimentally almost always lead to the formation of complex mixtures. Proposed polymer replication schemes are unlikely to succeed except with reasonably pure input monomers. No solution of the origin-of-life problem will be possible until the gap between the two kinds of chemistry is closed. Simplification of product mixtures through the self-organization of organic reaction sequences, whether cyclic or not, would help enormously, as would the discovery of very simple replicating polymers. However, solutions offered by supporters of geneticist or metabolist scenarios that are dependent on “if pigs could fly” hypothetical chemistry are unlikely to help
Yes, that is right, he got "if pigs could fly" into a paper. He was a great scientist. And it is nice for me to see one more paper of his. And this one, unlike pigs, can fly forever, because it is truly OA.
Saturday, January 19, 2008
There was an extensive article about this study in the New York Times on 1/15/08 (by John Noble Wilford). Overall the Times article is good (except Wilford gets the definition of phylogenetic analysis a bit wrong - saying it is the study of the evolutionary relationships between organisms when really it is the study of evolutionary relationships of anything... but hey that is OK).
I confess I am not sure if I am completely convinced by all of Harper et al's arguments concerning the evolution of these bugs. My main concern is that the amount of variation they observe (in ~ 20 genes across these strains) is very very low. And thus the resolution of the phylogenetic trees is quite poor.
Because this is a PLoS paper, it is truly "Open Access" and I can include the Figure here in my blog as long as I cite the original source (see below). If you look at the tree you can see some #s on the branches in the tree. These are based on a statistical test called bootstrapping and the numbers indicate (roughly) how well the tree that is shown represents all of the polymorphisms in the data. The #s are percentages and alas the % support is not very high for many of the branches. So a better resolution of the question of the origin of these diseases will likely require, well, a better resolution on the tree. This in turn will likely require complete genome sequences and perhaps more strains samples. Nevertheless, given the results they have, their arguments seem sound ... and this should stimulate people to gather more genomic data from these bugs.
Also see some other blogs on this
- Neil Woodburn
- John Dennehy (who mentions an article by Carl Zimmer in a non OA publication ... find out which by going to his blog)
Here is Figure 3. It is from Harper KN, Ocampo PS, Steiner BM, George RW, Silverman MS, et al. (2008) On the Origin of the Treponematoses: A Phylogenetic Approach. PLoS Negl Trop Dis 2(1): e148. doi:10.1371/journal.pntd.0000148
Figure 3. This maximum likelihood tree is based on 20 polymorphic regions in the T. pallidum genome. Bootstrap support was estimated with 1,000 replicates in order to assess confidence at branching points and are shown within circles where values are high (>90%). Bootstrap support values for both maximum likelihood and maximum parsimony trees are shown, in that order.
Tuesday, January 15, 2008
OK --- dipping into the gutter here a bit. But everyone must check out the cover of Nature this week. The issue is on the genetics of sex, and I'll be damned if that phycomyces colony on the cover (the one in the back) does not look like some sort of male sexual organ.
Monday, January 14, 2008
The following Chairs/Speakers (in alphabetical order) have been confirmed so far:
Friday, January 11, 2008
Thanks to Doug Rusch for pointing me to this video of a talk by Michael Shermer. It is a bit over the top, but I like the bit at the end suggesting that open access to information can basically stop wars.
Not sure I buy into the whole argument, but I do think that keeping scientific information behind closed walls is generally a bad idea ....
Thursday, January 10, 2008
It was a generally insightful phylogenomic tour of the evolution of opsins and eyes in animals. He also mentioned a paper he had recently in PLoS One on Animal Opsin evolution. This is from the work of his graduate student David Plachetzki and it does a nice job of doing "phylogenomic" analysis in the way I think of phylogenomics -- that is -- a integration of evolutionary and genomic analyses. (NOTE - I think it is kind of lame that people use the term phylogenomics, which I coined by the way, to refer to "using genomes to infer evolutionary trees). It is a paper worth checking out if you are interested in the origin of novelty.
I am putting links here to some of their figures and embedding them in this blog because, well, I can since PLoS One uses a broad Creative Commons license. For example - see Figure 6 from their paper below (the citation is Plachetzki DC, Degnan BM, Oakley TH (2007) The Origins of Novel Protein Interactions during Animal Opsin Evolution. PLoS ONE 2(10): e1054. doi:10.1371/journal.pone.000105).
Figure 6. Ancestral state reconstruction of G protein-binding interactions for each metazoan opsin-mediated phototransduction cascade obtained by simulated mutational mapping  (see methods).For each class of opsin, the P value of the reconstructed ancestral G α interactions is represented in pie graphs. Ancestral G protein interactions in phototransduction cascades mediated by ciliary, rhabdomeric and Go opsins can be significantly resolved (P>0.95) but the ancestral states of the rhabdomeric+Go, and cnidops clades are equivocal. ML state reconstructions shown for each node as colored branches. Red, Gi/t; Blue, Gq; Green, Go; Black, no G protein interaction (as is the case for RGR/Retinochrome opsins); Grey, equivocal reconstruction from ML. Reconstructed ancestral amino acid motifs of the 4th cytoplasmic loop region of opsin are shown along branches in logos. Maximum vertical height scales to P = 1.0. We obtained clear reconstructed states for most of the residues in a conserved tripeptide motif (residues 310, 311 and 312, horizontal bar) for the ciliary, rhabdomeric and Go /RGR nodes. For the most part, the remainder of the residues in can be unequivocally reconstructed to the level of Dayhoff classes. B = HRK, X = LIVM, J = GATSP, Z = DENQ..
See also Figure 2
"Figure 2. Unrooted metazoan-wide phylogeny of opsins, new cnidarian genes in bold, branches proportional to substitutions per site. Circles at nodes indicate Bayesian posterior probabilities (White = 1.0, Red>0.90, Blue>0.80, Green>0.70, Yellow>0.60, Black>0.50). cil = ciliary, rh = rhabdomeric."
Monday, January 07, 2008
Steve Salzberg has summary information and some comments here.
Popular Mechanics has some info here
The ever active Bora has some comments here
Wired has a bit here
My little bit .... I think science is clearly not strongly supported by the current administration. However, scientists need to be careful about how they word things, since in the end, we are asking for money from taxpayers to, well, pay our salaries and pay for our work. This is one of the reasons I am very strongly in support of "open science." The more open we scientists are, I think, the easier it is to justify to the "public" that we deserve some of their/our money. That is not to say that lots of taxpayer money is not completely wasted on other things. And even not completely open science is frequently good for the world. But openness should help make scientists not seem so ivory toweresque and would show that we want to give back in exchange for what we are given.
Sunday, January 06, 2008
Friday, January 04, 2008
In the review Hartl tells a story about an encounter with Max Delbrück at Cold Spring Harbor where Delbruck implied that molecular aspects of evolution were uninteresting. Hartl goes on to say many nice things about our book (he does get on our case about having problems on the web and not in the book - but hey nobody is perfect). My favorite from the review is the following
Textbooks in evolutionary biology have gen-Thanks Dr. Hartl. And a much belated thanks for a personal encounter that I had with you many years ago where you were MUCH more encouraging to me about working on bacterial genomes than Delbruck was to you about molecular evolution.
erally kept pace with these changes and several
excellent books are available. This new one by
Barton and colleagues is among the best. The
production quality is superb in layout, compo-
sition, typesetting, colour palette, illustrations
and gorgeous half-tones; and the writing is
excellent, as one might expect from such a stel-
lar cast of experts in population genetics, palae-
ontology, human genetics, bacterial genomics
and developmental biology (respectively).
The selected key items that they discuss:
- Personal genomics
- Microbial communities
- Stem cells without embryos
- Brain repair
- Human genetic variation
Wednesday, January 02, 2008
His passing saddens me greatly. Sam was a curmudgeony guy at times, but also a great scientist and teacher. He was one of my mentors when I was in graduate school at Stanford. I was kind of a fish out of water --- trying to learn boinformatics in a lab that studies the cell biology of DNA repair processes. So I took a course from Sam Karlin and Volker Brendel and then spent three years meeting on and off with Sam in his office discussing various aspects of genome and gene sequence analysis. We did not always agree. But I think I learned more about bioinformatics from those meetings with Sam than from anything else I have done in my career.
Sam reminded me a lot of my grandfather (who was a physicist). We would meet to ostensibly talk about RecA (my favorite protein) or DNA composition (Sam's favorite thing at the time) or evolution or something or other. But Sam turned every meeting into some type of lesson about bioinformatics. We rarely got to our end goal, but that did not really matter.
So - in his honor I am going to start a new section of this blog --- the Something about Math in Biology or the SAM in Biology section ... stay tuned.
NOTE Lee Altenberg has a memorial page to him, consisting of his doctoral advisor genealogy: