What kid would want to study bacterial evolution when they grow up?

OK - I am a bit scared by this, because it shows how little I have changed since I was young. And in my memory, I was not a total science geek for my whole life (you know - I focus on the fact that in high school, I played baseball and hockey and other sports pretty seriously, I guess my memory skips over that I was captain of the math team too).

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.

Leslie Orgel - Still Speaking Wisely and Openly Even After Death

OK - my mind has been blown. Leslie Orgel, who just passed away recently, has a new Essay in PLoS Biology called "The Implausibility of Metabolic Cycles on the Prebiotic Earth." Anyone interested in the origin of life should check this out.

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 [5] 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.

Syphilis origin solved?

A new paper in PLoS Neglected Tropical Diseases attempts to tackle a rather sensitive topic - the evolutionary origin of treponematoses (i.e., diseases caused by bacteria in the genus Treponema including yaws, pinta, and the one everyone wants to know about - syphilis). The paper, by Kristin Harper and others uses evolutionary reconstructions to try and determine if good old Christopher Columbus played a role in bringing syphilis to the New World.

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.

Is that a sex organ on the cover of Nature?

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.  

I do not know where to go with this.  It has to be on purpose right?  Is this what they refer to in the cover caption as a "pseudo-sexual" structure?

And I know I am probably not supposed to say this as an obsessed supporter of Open Access publishing but I dream of the day Nature becomes a fully OA journal.   I still think PLoS Biology is a better journal, but Nature definitely has some good stuff there.

International Congress of Genetics --- you should all go ---

OK - I am a bit biased as I am chairing a session at this "International Congress of Genetics" meeting. But it does look pretty good. Plenary talks by Richard Axel, Liz Blackburn, Mario Capecchi, Rudy Kaenisch, Eric Lander, Svante Paabo and Phil Sharp. Sessions on many things, including (hint hint) - metagenomics. Other speakers are listed below. So - you really should consider going ...check out the website here.

Chairs/Speakers
The following Chairs/Speakers (in alphabetical order) have been confirmed so far: Ruedi Aebersold (ETH Zuerich, Zuerich, Switzerland) Steve Kay (Univ. California, USA) Leif Andersson (Univ. Uppsala, Uppsala, Sweden) Brian Kennedy (Washington Univ., Seattle, USA) Siv Andersson (Univ. Uppsala, Uppsala, Sweden) Daniel Kevles (Yale Univ., New Haven, USA) Hiroyuki Araki (NIG, Mishima, Japan) Amar Klar (NCI, Frederick, USA) Ana Barahona (UNAM, Tialpan, Mexico) Narry Kim (Seoul National Univ., Seoul, South Korea) Cori Bargmann (Columbia University, New York, USA) Arne Klungland (Univ. Oslo, Oslo, Norway) Nick Barton (Univ. Edinburgh, Edinburgh, Britain) Bartha Knoppers (Univ. Montreal, Montreal, Canada) David Baulcombe (Sainsbury Laboratory, Norwich, Britain) Daphne Koller (Stanford Univ., Standford, USA) Stephan Beck (UCL, London, UK) Arash Komeili (Univ. of California, Berkeley, USA) Hugo Bellen (Baylor College of Med., Houston, USA) Charalambos Kyriacou (Univ. Leicester, Leicester, Britain) Jeffrey Bennetzen (Univ. Georgia, Athens, USA) Ruth Lehmann (Skirball Institute, NYU, New York, USA) Shelley Berger (Wistar Inst., Philadelphia, USA) Ottoline Leyser (Univ. York, York, UK) Casey Bergman (Univ. Manchester, Manchester, UK) Thomas Lindahl (CRUK, South Mimms, UK) Anton Berns (nki, Amsterdam, The Netherlands) Klaus Lindpainter (Hoffmann-LaRoche, Basel, Switzerland) Bruce Beutler (Scripps Res. Inst., La Jolla, USA) Edison Liu (Genome Institute, Singapore) Ewan Birney (EMBL, Hinxton, UK) John M. Logsdon (Univ. Iowa, USA) Maria Blasco (CNIO, Madrid, Spain) Trudy Mackay (NCSU, Raleigh, USA) D.I. Boomsma (Netherlands Twin Register, Amsterdam, Netherlands) Partha P. Majumder (Indian Statistical Institute, Kolkata, India) Paola Bonfante (CNR, Torino, Italy) Marjori Matzke (Gregor Mendel Institute, Vienna, Austria) Nancy Bonini (Univ. Penn., Philadelphia, USA) Gunter Meister, MPI, Martinsried, Germany) Peer Bork (EMBL, Heidelberg, Germany) Gilean McVean (Univ. Oxford, Oxford, UK) Dan Bradley (Trinity College Dublin, Dublin, Ireland) David A. Micklos (Cold Spring Harbor, New York, USA) Steve Briggs (Univ. California, San Diego, USA) Andrew Moore (EMBO, Heidelberg, Germany) Maja Bucan (Pennsylvania Univ. Philadelphia, USA) Joe Nadeau (CWR Univ., Cleveland, USA) Margaret Buckingham (Institut Pasteur, Paris, France) Wolfgang Nellen (Univ. Kassel, Kassel, Germany) Edward Buckler (Cornwell Univ., Ithaka, USA) Laura Niedernhofer (Univ. Pittsburg, Pittsburg, USA) Jeremy Burdon (CSIRO-Plant Industry, Canberra, Australia) Jens Nielsen (Biocentrum, Lyngby, Denmark) A. Bernardo Carvalho (Rio de Janeiro Univ., Brazil) Howard Ochman (Uni. Arizona, Tucson, USA) Aravinda Chakravarti (Johns Hopkins Univ., Baltimore, USA) Peter Oefner (Univ. Regensburg, Regensburg, Germany) Deborah Charlesworth (Univ. Edinburgh, Edinburgh, Britain) Steve Oliver (Cambridge Univ., Cambridge, UK) Judy Cho (Yale Univ., New Haven, USA) Allen Orr (Univ. Rochester, Rochester, USA) George Church (Harvard Medical School, Boston, USA) Terry Orr-Weaver (MIT / Whitehead, Cambridge, USA) Andy Clark (Cornwell Univ., Ithaka, USA) Elaine Ostrander (National Human Genome Research Institute, Bethesda, USA) Lynn Cooley (Yale Univ., New Haven, USA) Sven Panke (ETH Zürich, Zürich, Switzerland) Max Cooper (Univ. Alabama, Birmingham, USA) Susan Parkhurst (Fred Hutchinson Cancer Res. Centre, Seattle, USA) Arjan de Visser (Univ. Wageningen, The Netherlands) Martin Parniske (Ludwig-Maximilians-Universität, Munich, Germany) Alain Dessein (Univ. de la Méditérranée, Marseille, France) Renato Paro (ETH Zürich, Basel, Switzerland) Barry Dickson (IMP, Vienna, Austria) Linda Partridge (Univ. College, London, UK) Andrew Dillin (Salk Inst., La Jolla, USA) Dinshaw Patel (Sloan-Kettering Institute, New York, USA) Anna Di Rienzo (Univ. Chicago, Chicago, USA) Hervé Philippe (Univ. Montreal, Montreal, Canada) John Doebley (College of Agricultural & Life Sciences, Madison, USA) Alfred Pühler (Univ. Bielefeld, Bielefeld, Germany) Denis Duboule (Univ. Geneva, Geneva, Switzerland) Nazneen Rahman (Institute of Cancer Research, Sutton, UK) Evan Eichler (Univ. Washington, Seattle, USA) Klaus Rajewsky (Harvard Univ., Boston, USA) Jonathan Eisen (Univ. California, Davis, USA) Erez Raz (MPI, Göttingen, Germany) Hans Ellengren (Evolutionary Biology Centre, Uppsala Univ., Sweden) André Reis (Univ. Erlangen, Erlangen, Germany) Jonathan Flint (Wellcome Trust, Oxford, UK) Hans-Jörg Rheinberger (MPI, Berlin, Germany) Veronica Franklin-Tong (Univ. Birmingham, Birmingham, UK) Francisco Rodriguez-Valera (Univ. Alicante, Spain) Kelly Frazer (Scripps, La Jolla, USA) Outi Savolainen (Univ. of Oulu, Oulu, Finland) Wolf Frommer (Carnegie Institution of Washington, Stanford, USA) John Schimenti (Cornell Univ. New York, USA) Martin Fussenegger (ETH, Zürich, Switzerland) Eran Segal (Weizmann Institute of Science, Rehovot, Israel) Anne-Claude Gavin (EMBL, Heidelberg, Germany) Hee-Sup Shin (KIST, Seoul, South Korea) Michel Georges (Univ. Liège, Liège, Belgium) Akira Shizuo (Osaka Univ., Osaka, Japan) Carla Green (Virginia Univ., Charlottesville, USA) Mikiko Siomi (Univ. Tokushima, Kuramoto, Japan) Jonathan Gressel (Weizmann Inst., Rehovot, Israel) Christina Smolke (Caltech, Pasadena, USA) Anthony Griffiths (Univ. British Columbia, Vancouver, Canada) David Smyth (Monash Univ., Melbourne, Australia) Roderic Guigó (CRG, Barcelona, Spain) Marla Sokolowski (Toronto Univ., Toronto, Canada) Chris Haley (Roslin Inst., Roslin, Britain) Allan Spradling (Carnegie Institution, Baltimore, USA) Mike Hall (Biozentrum, Basel, Switzerland) Didier Stainier (Univ. California, San Francisco, USA) Michael F. Hammer (Univ. Arizona, Tucson, USA) Karen Steel (Sanger Inst., Hinxton, Britain) Min Han (Univ. Colorado, Boulder, USA) Kári Stefánsson (deCODE Genetics, Reykjavik, Iceland) Mitsuyasa Hasebe (National Institute for Basic Biology, Okazaki, Japan) Lars Steinmetz (EMBL, Heidelberg, Germany) Christian Heintzen (Univ. Manchester, UK) Michael Stratton (Sanger Institute, Hinxton, Britain) Steven Henikoff (Fred Hutchinson CRC, Seattle, USA) Azim Surani (Cambridge Univ., Cambridge, Britain) Martin L. Hibberd (Genome Institute of Singapore, Singapore) Joseph Takahashi (Northwestern University, Evanston, USA) Adrian Hill (Oxford Univ., Oxford, UK) Diethard Tautz (MPI, Plön, Germany) Helen Hobbs (Univ. Texas, Dallas, USA) Chau-Ti Ting (National Taiwan Univ., Taipei, Taiwan) Eric Holub (Warwick HRI, Wellesbourne, UK) Franck Uhlman (Cancer Research UK, London, UK) Elisa Izaurralde (MPI, Tuebingen, Germany) John Wakeley (Harvard Univ., Cambridge, USA) Janet Jansson (Swedish Univ. of Agricultural Sciences, Uppsala, Sweden) Detlef Weigel (MPI, Tuebingen, Germany) Urs Jenal (Biozentrum, Basel, Switzerland) Sue Wessler (Univ. Georgia, Athens, USA) Nancy Jenkins (Biopolis, Singapore) Eric Wieschaus (Princeton Univ., Princeton, USA) (Nobel Laureate) Julie Johnson (Univ., Florida, USA) Shinya Yamanaka (Univ. Kyoto, Kyoto, Japan) Regine Kahmann (MPI, Margburg, Germany) Zhu Zhen (Genetics Inst., Beijing, China) Thomas Kaufman (Indiana Univ., Bloomington, USA) Huda Y. Zoghbi (Baylor College of Med., Houston, USA) Stefan Kaufmann (MPI, Berlin, Germany)

Can openness stop wars?

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 ....

PCR Humor

Not much to say - other than thanks to Jenna Morgan for sending this ...

Oakley Keeping his Eye on Evolution

I saw an interesting talk today and thought I would post on it. I was not expecting to be able to go to the talk as I was supposed to be at a workshop in San Francisco but had to bail on it because my kids have been sick. But I did go in to Davis for a brief spell to go to a seminar by Todd Oakley who gave a talk here today.

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 [64] (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 G_o opsins can be significantly resolved (P>0.95) but the ancestral states of the rhabdomeric+G_o, and cnidops clades are equivocal. ML state reconstructions shown for each node as colored branches. Red, G_i/t; Blue, G_q; Green, G_o; 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 G_o /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."

Science and the presidential election

Nothing really new from me here but saw some good blogs on the topic of science and the presidential election.

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.

More fun at Long's

OK. Just had to post something because this is getting comical. I went in to Long's in E. Davis the other day to pick up some prescription refills. I had requested the refills online through the Long's web site and received an email saying they were reads. When I got in to the store, they told me that the refills were not ready. This is funny because this was about the 15th or so time in a row that my prescriptions were not ready when I was told they would be. One time it was problems with the online system. Another time it was that they needed a new prescription from my Doctor. Sure prescriptions expire and that is not really Long's fault. But apparently, when my prescriptions expire they decide to send faxes to a doctor I used to have in Maryland, even though I moved over two years ago. I came in like four times once over two weeks and every time they person at the counter would say "We faxed a request to Dr. So and So' and I would say "That person has not been my doctor for years. My new doctor is Dr. So and So in Davis." and they would sit there and click away at the keyboard supposedly fixing things and then they would say "OK, we will send it to the new doctor" And then I would come back and the person would say "We faxed your doctor in Maryland but he has not responded". This happened over and over and over. I began to view it as a game. How many times could I come to the pharmacy and could they get something wrong? The good things was, the people at the Long's pharmacy were very very nice. The bad thing was, something always seemed to go wrong. For a while I tried to use their automated prescription refill system, but that always went wrong too. So instead now, since I live near Long's and go to the Nugget all the time, I view my trips to the Long's Pharmacy as kind of an experiment in how many different ways my prescriptions can get screwed up.

Shameless Self Promotion ---- Another Good Review on my New Evolution Textbook

Well, again, here is another shameless self promotion. We got another good review of the new Evolution Textbook on which I am a co-author. This one is by Dan Hartl and was in Nature OK, it is not an Open Access review, but as I have said before, I am obsessed about open access to research articles, not book reviews, etc.

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-
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).

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.

Microbial communities highlighted by MIT Technology Review: The Year in Biotech

The MIT Technology review has an interesting piece on the "Year in Biotech". See Technology Review: The Year in Biotech

The selected key items that they discuss:

• Personal genomics
• Microbial communities
• Stem cells without embryos
• Brain repair
• Human genetic variation

Good to see microbial communities getting selected for this type of thing --- they are after all the next big thing.

In memory of Sam Karlin

I just got an email telling me that Sam Karlin had passed away. Sam, for those who do not know, was one of the luminaries in bioinformatics and mathematical biology. You can learn a bit more about him by going to this site which relates to a workshop that was help in honor of his 80th birthday.

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: