Decoding the Structure of the HIV Genome

 
The title of the press release on Biology News Net caught my eye: UNC researchers decode structure of an entire HIV genome. I clicked the link on my aggregator and read the first two paragraphs.

The structure of an entire HIV genome has been decoded for the first time by researchers at the University of North Carolina at Chapel Hill. The results have widespread implications for understanding the strategies that viruses, like the one that causes AIDS, use to infect humans.

The study, the cover story in the Aug. 6, 2009, issue of the journal Nature, also opens the door for further research which could accelerate the development of antiviral drugs.

By the time I finished the article I thought I had a pretty good idea of what they were talking about but, just to be sure, I visited the Nature website to read the actual scientific paper.

Watts, J.M., Dang, K.K., Gorelick, R.J., Leonard, C.W., Bess Jr., J.W., Swanstrom, R., Burch, C.L. and Weeks, K.M. (2009) Architecture and secondary structure of an entire HIV-1 RNA genome. Nature 460:705-710 [doi: 10.1038/nature08237]

Single-stranded RNA viruses encompass broad classes of infectious agents and cause the common cold, cancer, AIDS and other serious health threats. Viral replication is regulated at many levels, including the use of conserved genomic RNA structures. Most potential regulatory elements in viral RNA genomes are uncharacterized. Here we report the structure of an entire HIV-1 genome at single nucleotide resolution using SHAPE, a high-throughput RNA analysis technology. The genome encodes protein structure at two levels. In addition to the correspondence between RNA and protein primary sequences, a correlation exists between high levels of RNA structure and sequences that encode inter-domain loops in HIV proteins. This correlation suggests that RNA structure modulates ribosome elongation to promote native protein folding. Some simple genome elements previously shown to be important, including the ribosomal gag-pol frameshift stem-loop, are components of larger RNA motifs. We also identify organizational principles for unstructured RNA regions, including splice site acceptors and hypervariable regions. These results emphasize that the HIV-1 genome and, potentially, many coding RNAs are punctuated by previously unrecognized regulatory motifs and that extensive RNA structure constitutes an important component of the genetic code.

The authors determined the two- and in some cases the three-dimensional structure of the HIV RNA genome. In other words, they figured out the way RNA folds to form regions of secondary structure (double-stranded RNA). This RNA molecule functions as a complex messenger RNA and the secondary structure plays a role in regulating how the molecule is translated.

The press release doesn't really convey this result very well, especially in the opening paragraph. Part of the problem is misue of the word "decode." We're familiar with journalists who use "decode" to mean "nucleotide sequence" as in "Scientists decoded the human genome." This elevates "decode" to an entirely new meaning.

In fairness, this confusion over the word "decode" is exacerbated by the language used by the authors in the paper.

Our discovery that the peptide loops that link independently folded protein domains are encoded by highly structured RNA indicates that these and probably other mRNAs encode protein structure at a second level beyond specifying the amino acid sequence. In this view, higher-order RNA structure directly encodes protein structure, especially at domain junctions. The extraordinary density of information encoded in the structure of large RNA molecules (Figs 1, 2 and 4d) represents another level of the genetic code, one which we understand the least at present. This work makes clear that there is much to be discovered by broad structural analyses of RNA genomes and intact mRNAs.

I'm not sure this language is helpful.

UPDATE: The press release from Scientific American is different: HIV genome structure decoded.

It might not be super high-res, but researchers at the University of North Carolina at Chapel Hill have described the first full structure of the HIV-1 genome.

The paper, published online today in Nature, maps out the virus' genome down to a one-nucleotide resolution with the help of a technique call SHAPE—selective 2'-hydroxyl acylation analyzed by primer extension—to paint the full, previously unknown picture of the virus (Scientific American is part of Nature Publishing Group).

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Censorship in the Scientific Community

 
Richard Dawkins interviews Wendy Wright of Concerned Women for America. You really have to watch this if you want to understand what science is up against in some parts of the world.

Richard tries very hard to be patient and respectful. I would not have been so kind in the face of such massive stupidity and ad hominem attacks by Wendy Wright. I find it absolutely astonishing that she attacks scientists and accuses them of stupidity and conspiracy then complains about ad hominem attacks when Richard asks why she rejects evolution.








I don't know how much of this you can stand. Parts 5, 6, and 7 are here.

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Monday's Molecule #132: Winner!

 
This is a complex between parts of the T-cell receptor (green and blue) and the major histocompatibility complex class II molecule (MHC class II) shown in orange and yellow. There's a peptide bound in the presentation site of the class molecule (red).

When a cell becomes infected with a virus, various viral proteins are broken down into peptides and bound to a site on class II molecules. These molecules are then presented on the surface of the cell when they can be recognized by the T-cell receptor. Since the viral peptide will be seen as a foreign antigen, the infected cell will be destroyed.

The Nobel Laureates are Rolf Zinkernagel and Peter Doherty.

There weren't very many correct answers this week¹ but Markus-Frederik Bohn thought it was very easy. He's a graduate student at the Lehrstuhl für Biotechnik in Erlangen, Germany. He has a Canadian connection but I'll let him reveal it in the comments if he wishes.

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This is a very famous molecular complex. You need to identify this complex by naming all the major components. You will not win if you skip this part. (Don't forget the red bit.)

There is a Nobel Prize associated with the discover of this complex although the work was done long before the structure was solved. The first person to identify the molecules and the Nobel Laureate(s), wins a free lunch. Previous winners are ineligible for six weeks from the time they first won the prize.

There are only five ineligible candidates for this week's reward: Dima Klenchin of the University of Wisconsin at Madison, Dara Gilbert of the University of Waterloo, Anne Johnson of Ryerson University, Cody Cobb, soon to be a graduate student at Rutgers University in New Jersey, and Alex Ling of the University of Toronto.

I have an extra free lunch for a deserving undergraduate so I'm going to continue to award an additional prize to the first undergraduate student who can accept it. Please indicate in your email message whether you are an undergraduate and whether you can make it for lunch.

THEME:

Nobel Laureates
Send your guess to Sandwalk (sandwalk (at) bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the molecule(s) and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Prizes so you might want to check the list of previous Sandwalk postings by clicking on the link in the theme box.

Correct responses will be posted tomorrow.

Comments will be blocked for 24 hours.

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1. Because immunology isn't biochemistry and possibly not even a real science.

The figure is from Reinherz et al. (1999).

Reinherz, E.L., Tan, K., Tang, L., Kern, P., Liu, J., Xiong, Y., Hussey, R.E., Smolyar, A., Hare, B., Zhang, R., Joachimiak, A., Chang, H.C., Wagner, G., and Wang, J. (1999) Science 286:1913-1921. [PubMed] [doi: 10.1126/science.286.5446.1913]

Lateral Gene Transfer and the Return of Lamarckian Evolution

 
Mark Buchanan believes that physics has entered a new era where it has gone beyond the fundamental forces into the realm of "collective phenomena". He claims that biology is about to do the same as he explains in an article that was just published in Nature Physics: "Collectivist Revolution in Evolution."

It now seems clear that biology may also have a second act linked to the widespread importance of collective phenomena. The explosion of genetic and genomic data, of course, has ushered in the era of systems biology, as biologists have come to recognize the need to gain a more holistic understanding of the functioning of organisms. But this may not be the most radical transformation in store for biological science. A coming revolution in biology, some suggest, may go so far as to unseat Darwinian evolution (ran in its modern form) from its position as the key explanatory process in biology, and may just bring back some form of Lamarckian evolution—that old idea of the inheritance of acquired characteristics.

No, it's not epigenetics, it's lateral gene transfer (LGT) that's going to unseat Darwinian evolution and bring back Lamarck.

Much of what he writes about LGT is correct. It does, indeed, make interpretation of molecular evolution more difficult, especially at the root. But some of his ideas do not represent the consensus view in biology: for example, the role of lateral gene transfer in the evolution of the genetic code.

The conjecture is that horizontal gene transfer was indeed required for the present genetic code to take the form it has, and that the emergence of life most likely went through a series of stages, with the early stage more Lamarckian in character, and only the latter stages becoming more Darwinian.

Exploring that point in greater detail will be a task for a new kind of biology, one that breaks with many of the presuppositions of traditional evolutionary thinking, and explores the potential for rich and surprising dynamics in a collective setting. It will almost surely benefit from the ideas and experience of physics, which has already experienced its own collectivist revolution.

This kind of hyperbole is not helpful. Shame on Nature Physics for publishing it.¹

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1. I wonder if Nature Genetics publishes opinion pieces by evolutionary biologists on the overthrow of quantum mechanics?

NIH and Francis Collins

 
I wish that Obama had picked someone else as his nominee for Director of NIH. I'm not opposed to Collins simply because he is religious. I'm opposed to him because he has taken a very public and vocal position on the roles of science and religion. Here's how I've expressed my viewpoint in comments on my own blog and elsewhere.

I'm not opposed to Collins just because he is an evangelical Christian. And I would not be opposed to someone from another faith, nor to an atheist.

But when a person becomes an outspoken advocate of a particular religious belief and establishes a foundation and a website to promote that belief (e.g. BioLogos) then that's a different story.

The banner on the BioLogos site reads, "We believe that faith and science both lead to truth about God and creation." Collins has gone beyond merely holding a belief that may or may not be compatible with science. He is now actively identified with a particular position; namely, that science and evangelical Christianity are compatible.

Not only that, Collins is on record favoring the use of his office to promote his personal religious beliefs [Mixing Science, Religion, and Politics].

It would be far better to appoint someone who could maintain a decent separation between religion and science. The Director of a major government funding agency should not be openly advocating a religious perspective on science.

It would be just as unwise to appoint a vocal atheist or a vocal Muslim.

This seems to be a difficult position for most people to grasp. PZ Myers shares my perspective on the appointment [Is it really that hard to understand?] but no matter how many times he tries to explain it, there's always someone who tries to turn it into an attack on all Christians. The latest is Matt Springer.

Religion should be kept out of scientific organizations whether they they are government run, like NIH, or collections of scientists like AAAS and NAS [What Should Scientific Organizations Say about Religion?, Theistic Evolution: How Does God Do It?]. By nominating someone with a strong, vocal, religious perspective, Obama is sending the wrong message.

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UCSC Official Mascot

 
Fred Zlotnick took this picture of a banana slug in his back yard.

Believe it or not, the banana slug is the official mascot of the University of California Santa Cruz.

The Banana Slug, a bright yellow, slimy, shell-less mollusk found in the campus's redwood forest, was the unofficial mascot for UC Santa Cruz's coed teams since the university's early years. The students' adoption of such a lowly creature for a team mascot was their reaction to the fierce athletic competition fostered at most American universities. UCSC has always offered a wide-ranging physical education and recreation program designed to appeal to the greatest number of students, but it has based its approach on some unusual ideas: that athletics are for all students, not just team members of major sports; that the most important goal of a collegiate physical education department should be to introduce as many students as possible to lifelong physical activities; and that the joy of participating is more important than winning.

In 1980, when some campus teams wanted more organized yet still low-key participation in extramural competition, UCSC joined Division III of the NCAA in five sports. Since the application required an official team name, UCSC's then chancellor polled the student players, and out of this small group emerged a consensus for a new moniker--the sea lions. It was a choice that the chancellor considered more dignified and suitable to serious play than the Banana Slugs. But the new name did not find favor with the majority of students, who continued to root for the Slugs even after a sea lion was painted in the middle of the basketball floor.

After five years of dealing with the two-mascot problem, an overwhelming proslug straw vote by students in 1986 convinced the chancellor to make the lowly but beloved Banana Slug UCSC's official mascot. By the time the chancellor had left office, he was won over to the proslug camp, even to the point of featuring the Slug on his personal holiday card.

In May 2004, Reader's Digest named the Banana Slug the best college mascot. The Banana Slug even figured in a court case involving campus mascots. Judge Terence Evans, writing the opinion for the Seventh Circuit Court of Appeals, stated the following: "We give the best college nickname nod to the University of California, Santa Cruz. Imagine the fear in the hearts of opponents who travel there to face the imaginatively named 'Banana Slugs'?" (Crue et al. v. Aiken, June 1, 2004)

Our Sammy the Slug mascot has been appearing around campus at sports events and other functions. And, when the men's tennis team played in the NCAA championships, their T-shirts read: "Banana Slugs-No Known Predators."

UC Santa Cruz Foundation trustee Anne Neufeld Levin wrote a children's book, Sally Slug, illustrated by UCSC alumna and former Foundation trustee Patricia Rebele. The book, published in 2002, is available at slugstore.ucsc.edu. Proceeds from sales of the book benefit the UCSC Foundation and provide for art history purchases and exhibits in the library.

Sounds like my kind of school. I wonder if they need a biochemistry Prof?

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Is "Organic" Food Better for You than "Conventionally" Produced Food?

 
The London School of Hygiene and Tropical Medicine has just completed a study of the scientific literature commissioned by the Food Standards Agency in the UK [Comparison of composition (nutrients and other substances) of organically and conventionally produced foodstuffs: a systematic review of the available literature].

According to the press release ...

An independent review commissioned by the Food Standards Agency (FSA) shows that there are no important differences in the nutrition content, or any additional health benefits, of organic food when compared with conventionally produced food. The focus of the review was the nutritional content of foodstuffs.

Gill Fine, FSA Director of Consumer Choice and Dietary Health, said: ‘Ensuring people have accurate information is absolutely essential in allowing us all to make informed choices about the food we eat. This study does not mean that people should not eat organic food. What it shows is that there is little, if any, nutritional difference between organic and conventionally produced food and that there is no evidence of additional health benefits from eating organic food.

'The Agency supports consumer choice and is neither pro nor anti organic food. We recognise that there are many reasons why people choose to eat organic, such as animal welfare or environmental concerns. The Agency will continue to give consumers accurate information about their food based on the best available scientific evidence.’

This makes a lot of sense. There was never a good reason for assuming that organically grown foods would be more healthy than conventionally grown food and now we have scientific evidence to support that assumption. From now on, whenever you hear someone say that "organic" foods are more healthy you can inform them that what they are saying is contrary to scientific evidence.

There may be other reasons for wanting to eat organically grown food. It may be better for the environment and it may contain fewer traces of pesticides and herbicides. Those claims haven't been refuted by this study. (Although, as far as I know, there's no scientific reason to believe that treating food with herbicides and pesticides is dangerous to the consumer. Besides, organic food is also treated.)

You may wonder why this is such a big deal. Maybe you never thought that organic food was more nutritious than conventionally grown food. If so, you are one of the more rational consumers. Most other consumers are more inclined to believe what the image above shows and what they think are scientific studies proving that organic food is better. That image is from this report in the Daily Mail from 2007: Organic food really IS better for you, claims study.

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[Image Credit: The top image is from Green Expander where they say, "Organic food is becoming more and more popular. This is the healthy food, without any additives, with higher levels of vitamin C and essential minerals. Organic food comes from trusted farms and food companies, that are inspected at least once a year."]

Land Snails and Slugs

 
Most of us don't know very much about slugs and land snails but Christopher Taylor at Catalogue of Organisms is doing his best to educate us (and himself): Wild Slug Chases (Taxon of the Week: Gastrodontoidea).

I need to warn you that his posting isn't suitable for all audiences. Some of these animals are capable of having sex with themselves and that's not something you want your children to know. Also, some of these animals aren't as pretty as warm fuzzy animals like cats. I find it helps to think of snails and slugs as dinner rather than pets.¹

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1. For some people, this works for cats too.

Monday's Molecule #132

 
This is a very famous molecular complex. You need to identify this complex by naming all the major components. You will not win if you skip this part. (Don't forget the red bit.)

There is a Nobel Prize associated with the discover of this complex although the work was done long before the structure was solved. The first person to identify the molecules and the Nobel Laureate(s), wins a free lunch. Previous winners are ineligible for six weeks from the time they first won the prize.

There are only five ineligible candidates for this week's reward: Dima Klenchin of the University of Wisconsin at Madison, Dara Gilbert of the University of Waterloo, Anne Johnson of Ryerson University, Cody Cobb, soon to be a graduate student at Rutgers University in New Jersey, and Alex Ling of the University of Toronto.

I have an extra free lunch for a deserving undergraduate so I'm going to continue to award an additional prize to the first undergraduate student who can accept it. Please indicate in your email message whether you are an undergraduate and whether you can make it for lunch.

THEME:

Nobel Laureates
Send your guess to Sandwalk (sandwalk (at) bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the molecule(s) and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Prizes so you might want to check the list of previous Sandwalk postings by clicking on the link in the theme box.

Correct responses will be posted tomorrow.

Comments will be blocked for 24 hours. Comments are now open.

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The figure is from Reinherz et al. (1999).

Reinherz, E.L., Tan, K., Tang, L., Kern, P., Liu, J., Xiong, Y., Hussey, R.E., Smolyar, A., Hare, B., Zhang, R., Joachimiak, A., Chang, H.C., Wagner, G., and Wang, J. (1999) Science 286:1913-1921. [PubMed] [doi: 10.1126/science.286.5446.1913]

Breakthrough!! The Third Replicator Is Discovered

 
The editors at New Scientist have become completely incapable of distinguishing between science and things that pretend to be science. The latest evidence of this failing is an article by Susan Blackmore titled: Evolution's third replicator: Genes, memes, and now what?.

WE HUMANS have let loose something extraordinary on our planet - a third replicator - the consequences of which are unpredictable and possibly dangerous.

What do I mean by "third replicator"? The first replicator was the gene - the basis of biological evolution. The second was memes - the basis of cultural evolution. I believe that what we are now seeing, in a vast technological explosion, is the birth of a third evolutionary process. We are Earth's Pandoran species, yet we are blissfully oblivious to what we have let out of the box.

This might sound apocalyptic, but it is how the world looks when we realise that Darwin's principle of evolution by natural selection need not apply just to biology. Given some kind of copying machinery that makes lots of slightly different copies of the same information, and given that only a few of those copies survive to be copied again, an evolutionary process must occur and design will appear out of destruction.

But all is not lost. One of the benefits arising out of the self-destruction of New Scientist is that it gives us all a chance to watch a train wreck in action.

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[Photo Credit: Train Wreck at Gare Montparnasse, Paris, France, 1895 from Answers.com]

Happy Simcoe Day!!

 

Today is Simcoe Day in Toronto, a holiday named after John Graves Simcoe, the first Lieutenant Governor of Upper Canada (1791-1796).

According to Wikipedia ...

He founded York (now Toronto) and was instrumental in introducing institutions such as the courts, trial by jury, English common law, freehold land tenure, and for abolishing slavery in Upper Canada long before it was abolished in the British Empire as a whole (it had disappeared from Upper Canada by 1810, but was not abolished throughout the Empire until 1834).

The holiday is known by many other names in other parts of Canada including the term "Civic Holiday," a name that brings tears to your eyes.

I think the entire country should name this holiday "Simcoe Day" in honor of John Graves Simcoe, the founder of Toronto, which is, after all, the greatest city in Canada. If Canada were to officially recognize the superiority of Toronto (and Torontonians) it would go a long way toward unifying the country.

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Free Health Care Clinic in a Country that Needs It

 
Remote Area Medical (RAM) is a group of doctors, optometrists, dentists, nurses etc. who donate their time to setting up free temporary clinics in primitive places where the natives don't have access to affordable heath care.

Here's a video of this year's annual clinic in Wise County, Virginia. Isn't it strange that such an event is held in a country with the best health care in the entire world?



I got this from Jennifer Smith at Runesmith's Canadian Content: This was Wendell Potter's Epiphany. Read her blog.

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An Educational Lunch

 
Last week, before leaving for Halifax, I had lunch with David Schuller (a Monday's Molecule winner) and Deb Breiter. They were in town for a meeting of crystallographers.

We talked about biochemistry education (among other things) and it was fun to hear the perspective of someone who teaches introductory biochemistry at a smaller college in the mid-west. (Deb is head of the Department of Chemistry and Biochemistry at Rockford College in Illinois.)

The issues she faces are very different than those at a big school like the University of Toronto. Naturally we talked about textbooks and, after scolding her for not using my book, we debated the merits of various introductory biochemistry textbooks. (She has used several different ones and is very knowledgeable on the topic.)

Part of the debate revolves around differing approaches to teaching introductory biochemistry. There are many variations but I like to think of two main ones that I refer to as the "Evolutionary Approach" and the "Fuel Metabolism" approach.¹ Keep in mind that these are just broad categories used to illustrate some points about how to teach biochemistry.

The Evolutionary Approach to biochemistry emphasizes universal concepts that apply to most organisms. It concentrates on comparative aspects of biochemistry and on explanations of where things come from. This approach will almost always include lectures on photosynthesis and will almost always try to explain how metabolic pathways evolve.

In the Evolutionary Approach, the fundamental pathways of lipids, carbohydrates, amino acids etc. are the biosynthetic ones and not the degradation pathways. Some concepts, like the idea of essential amino acids, are relegated to footnotes. Human biochemistry is treated as a specialized version of the big picture and the fundamental concepts are taught first using simple prokaryotic examples.

The Fuel Metabolism Approach is quite different. Here the emphasis is on human biochemistry and almost everything is treated as a potential fuel before its biosynthesis is discussed. Photosynthesis isn't covered in such a course and the biochemistry of bacteria is usually not mentioned. This is the kind of course that's geared for students who are interested in their own metabolism and (it is thought) for pre-medical students.

In the Fuel Metabolism approach, students will learn that gluconeogenesis isn't very important and that there's a big difference between essential and nonessential amino acids. They will learn that the carbons in fatty acids can rarely be converted to carbohydrates. They will study transcription, translation, and DNA replication as they occur in mammals and they usually won't be exposed to the prokaryotic versions of information flow.

I think that the Evolutionary Approach to biochemistry is superior to the older Fuel Metabolism approach. In part, this is because the Evolutionary Approach encourages a "big picture" view of biochemistry where the ideas are more important than the facts. In contrast, the Fuel Metabolism approach encourages the learning of specific pathways since, by and large, it is confined to discussing mammals.

On the other hand, the Fuel Metabolism Approach may be more appealing to students because they are more concerned about themselves than about other species. Furthermore, it lends itself to discussions about diet and nutrition and these are hot topics that attract students.

I learned a lot from Deb Breiter. One of the most important things was that teachers like her get together from time to time to discuss how to teach chemistry/biochemistry. The meetings I attend are dominated by people who write textbooks and run BAMBED (Biochemistry and Molecular Biology Education) and we don't have much contact with many of those on the front line. (Don't get me wrong, most of us at those meetings are also teachers, it's just that we tend to forget that the vast majority of biochemistry teachers aren't even aware of some issues.)

Deb belongs to a group called the "Midwestern Association of Chemistry Teachers in Liberal Arts Colleges" (MACTLAC). The MACTLAC 2009 Annual Meeting is at Hope College in Michigan on Oct. 16-17. It would be fun to attend—I wonder if they allow interlopers?

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1. Many textbook authors refer to the Fuel Metabolism Approach as "rat liver" biochemistry but I won't mention that here because it sounds like I'm taking sides.

Perspectives on the Tree of Life: Day Two

The second day began bright and early with a talk by Jeffrey Lawrence, professor of biology at the University of Pittsburgh, Pittsburgh (PA, USA).

The title of his talk, Fragmented speciation in bacteria: The failure of the coalescent model doesn't really reflect its significance. Jeff showed us his careful analysis of speciation in bacteria focusing on a small clade of bacteria including Escherichia coli, and its closest relatives, Citrobacter kosteri, Salmonella enterica, Enterobacter sp., Klebsiella pneumonia etc.

When "speciation" occurs in bacteria there is considerable lateral gene exchange that obscures the actual relationship. What this means is that there really is no single common ancestor of most pairs of species and, given that it is almost impossible to define a species in the first place, a single phylogenetic tree of organisms is not a correct depiction of the tree of life.

Imagine a situation where our human ancestor was hanging out with the ancestors of gorillas and chimpanzees and a lot of gorilla ancestral genes made it into our genome. We wouldn't be able to depict the true representation of our evolution by just showing a simple bifurcating tree where we are closest to chimpanzees and more distant from gorillas. This treelike representation would ignore the transfer of genes between our ancestor and that of gorillas. You need a net or a web to show the actual path of descent. That's the situation in bacteria, as we saw clearly in the presentation.

But the failure of genomes to coalesce to a single ancestor doesn't make the whole exercise useless. It's still possible to say that Escherichia coli, Citrobacter kosteri and Salmonella enterica are more closely related to each other that any of them are to Klebsiella pneumoniae. Jeff gave us some estimates of the frequency of lateral gene transfer but I didn't write them down. The general consensus at the meeting is that DNA from another species is incorporated at the rate of once every few million years. This is enough to seriously compromise a treelike phylogeny.

Greg Morgan is a philosopher who is currently at a college in New Jersey. He gave the second talk. His title was Defining biodiversity in a world with horizontal gene transfer. He was mainly critiquing a book by the philosophers Maclaurin and Sterelney on biodiversity. Their concept of a species doesn't take lateral gene transfer into account and it doesn't really pay attention to the microbial world and the definition of species. Greg emphasized that there are many ways to define biodiversity and it makes a difference if you are interested in preserving biodiversity.

Laura Franklin-Hall is a philosopher at New York University in New York (NY, USA).Her presentation was an attempt to root for the underdog by defending trees: Scientific models and the history of life: Deep disagreement or mere misunderstanding?

I wish I had time to explain her description of scientific models and how they work but I didn't take enough notes and, besides, I'm still digesting the information. The idea is that no model is perfect—they all suffer from various weaknesses—and we shouldn't necessarily opt for the model that incorporates the most detail. In other words, while a web or a net may be a more accurate description of descent with modification, there's still a lot to be said for a tree if it represents some underlying, but partial, truth.

Maureen O'Malley is a philosopher at the University of Exeter and a former colleague of Ford Doolittle's. She is one of the behind-the-scenes organizers of the meeting. Her talk was on The philosophy of evolution, Ernst Mayr and the tree of life. She gave a really interesting summary of Mayr's views on evolution—a view which obviously didn't consider microbes and didn't concentrate on genes ("beanbag genetics").

I think its fair to say that most evolutionary biologists in the room found it interesting to review the history of Mayr's thoughts, but that's all it was; history. The philosophers, on the other hand, were much more attentive. Apparently Mayr is thought of as one of the founding fathers of the philosophy of biology and an "attack" on Mayr is close to blasphemy. That's shocking to me and it suggests that philosophers of biology are very much out of touch with modern evolutionary biology. This observation is consistent with some of the things that went on at this meeting although I hasten to add that most of the philosophers here seem to have a much more modern perspective. They weren't the least bit unhappy to see Mayr dethroned.

(I gather that photographs of Maureen are unusual. That's why the group photo at the top of the page is so important. She's right there in the second row.)

Eric Bapteste is a philosopher at IHPST in Paris (France). He told us how important it is to incorporate Lateral thinking about trees into our view of evolution. By "lateral thinking" he means the idea that genes can be inherited horizontally and not just vertically.

Lisa Gannet is a philosopher at St. Mary's University here in Halifax (NS, Canada). Her talk was on the difficulties in reconstructing the history of human populations and the various ways of representing it. Much of her talk was peppered with references to racism and it became apparent that she is very concerned about whether a tree of humans populations might support racism. After her talk I asked her about this and it turns out she is one of those people who don't think that human races exist.

The next talk was by James Mallet, a biologist at the Galton Laboratory, University College London, London (UK). The title of his talk certainly got everyone's attention: Was Darwin wrong about the nature of species and speciation?. Jim began by quoting Ernst Mayr, who in several papers, made the point that Darwin was wrong about speciation. Mayr quoted directly from Darwin's works to support the idea that he (Darwin) had an incorrect view of speciation.

Jim demolished that idea by showing that Mayr was as guilty of quote-mining as our typical creationist friends. It turns out that Darwin's ideas on species and speciation were far more accurate than Mayr was willing to admit and it's time we acknowledged that. Jim went on to illustrate real examples of speciation by looking at various races and varieties of butterflies in Venezuela. Just as Darwin imagined, there's a smooth continuum from varieties, races, and subspecies to real speciation events and it's often difficult to distinguish between races and species. Many species interbreed to form hybrids, as he showed using his data, but the hybrids might be quite rare indicating that gene flow between the species is almost nonexistent.

The last talk was by Richard (Dick) Burian, a philosopher at Virgina Tech in Blacksburg (VA, USA). He spoke about "Some conceptual issues deriving from the challenges to tree thinking. The emphasis was on identifying the "process" that can explain the "pattern" of evolution. This becomes difficult in the face of chimeras and symbiosis. Dick tried to establish the criteria that these processes had to fulfill in order to be legitimate contenders in the explanation of evolution. One of the criteria was selection so I asked him whether random genetic drift was a process that could be used to explain the pattern of evolution. The answer was "no." After the talk we had a discussion about this and we both agreed to think about it.

We all went off to dinner at The Cellar restaurant. Much alcohol was consumed and this contributed greatly to the discussions. As usual. we went home satisfied that we have solved most of the problems and woke up forgetting the solutions. We'll try again tonight. I'm more convinced than ever that this is the best meeting I've ever attended. I'm learning things at such a furious rate that my brain is beginning to feel the pain.

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Perspectives on the Tree of Life: Day One

The meeting began with a brief introduction by John Dupré. The first speaker was Ford Doolittleof the Dept. of Biochemistry and Molecular Biology at Dalhousie University here in Halifax. His title was The Tree of Life, from three sides now.

Ford introduced the topic from three perspectives: science, philosophy, and politics. The science is straightforward. You can construct perfectly respectable gene trees for bacteria using all kinds of different genes. Problem is, the trees aren't congruent. They don't agree with each other. This is well-established scientific fact and you need to accept it if you're ever going to understand the issue.

The trees aren't wildly different in most cases and it's possible to make sense of them by postulating the transfer of genes from one species to a different species. This is horizontal gene transfer (HGT), as opposed to the normal vertical gene transfer from generation to generation. It's more common to use the term lateral gene transfer (LGT). There are three very well studied modes of transfer: conjugation, transduction, and transformation.

The scientific evidence shows clearly that early phylogenetic relationships among bacteria cannot be accurately represented by a single tree. The proper relationship is a net, network, or a web. Again, this is not controversial among those scientists who are aware of the data. The facts and the conclusion have been around for over a decade. There is no "tree of life" representing the early evolution of life on Earth.



The philosophical questions have to do with the usefulness of metaphors in science (e.g. tree) and the implications for understanding the history of biology. Do we need to abandon all talk of trees? Is "Darwinism" committed to tree-like interpretations of evolution? Ford spent more time than I would have liked discussing Darwin's thoughts about trees and, unfortunately, the famous New Scientist cover was prominently on display.

Later on, Ford made the point that we need to move beyond Darwinism to postDarwinism and I agree with this point. That's why we need to stop talking about what Charles Darwin did, or did not, believe. He was wrong about a lot of things, but he died over 125 years ago.

The politics part of the talk refers to the fact that questioning the tree of life cases problems for those who are fighting creationists. By challenging a fundamental concept in evolutionary biology we are lending support to the creationists. Ford said that he understands why Genie Scott and the people at NCSE might be upset about this and he understands why there might be some value in focusing on the validity of animal trees instead of drawing attention to the problems with bacterial trees.

Most people at the meeting felt that NSCE and everyone else involved in fighting creationists just have to suck it up and deal with the scientific facts.

The next talk was by Jan SappProfessor of Biology at York University in Toronto (ON, Canada). Sandwalk readers will recall that I devoted several postings to discussing his book on the Three Domain Hypothesis some years ago.

The title of Jan's talk was Thinking laterally on the tree of life. He emphasized history of trees in biology and the history of lateral gene transfer, including hybridization and symbiosis. As it turns out, scientists have been thinking about non-treelike inheritance for more than 100 years.

Jan has a new book coming out that will discuss this history and its implications for a new view of evolution.

The third speaker was Ian Hacking, Professor of Philosophy at the University of Toronto (ON, Canada). He talked about The Fatal Attraction of Trees. The idea is that we all have a preference for organizing information in a treelike manner and this bias gets in the way of accepting a different view of evolution.

Olivier Rieppel works at the Field Museum in Chicago (IL, USA). His talk was about The series,the network, and the tree: Changing metaphors of order in nature. Olivier spent some time on cladism and cladistics and raised interesting questions about the validity of cladism as an approach to phylogeny.

Here's the problem: even in vertebrates, the gene trees don't always agree with the morphological trees. Olivier works with snakes and lizards and sorting out the "true" evolutionary history is extremely difficult. Is there a lot of LGT in vertebrates? Is it possible that we might have to abandon trees even at the this level?

Rob Beiko works in the Faculty of Computer Science at Dalhousie University in Halifax (NS, Canada). He showed us how LGT can mess up your trees. He developed computer simulations to illustrate the effect of lateral genes transfer under various condition. The good news is that reasonable frequencies of lateral gene transfer don't completely obscure the underlying treelike phylogeny.

Yan Boucher is a postdoc at MIT in Boston (MA, USA). His talk was Evolutionary Units: Breaking down species concepts. The main idea was that we should not consider species as the unit of evolution, instead, the appropriate unit is a piece of DNA. This was by far the most controversial talk. Several participants, including me, were quite confused by the presentation. We weren't aware of the fact that a species was considered a unit of evolution.

The next speaker was Peter Gogarten of the University of Connecticut in Storrs (CT, USA). Peter showed us many examples of lateral gene transfer in bacteria.

Joe Velasco is in the Dept. of Philosophy at Stanford University in Palo Alto (CA, USA). He told us about strategies for Inferring phylogenetic networks from a hypothetical computational approach. The bottom line is that it make be possible to construct networks—as opposed to trees—using computer programs but it's going to take a huge amount of effort.

After the talks we retired to the pub at the University Club and dinner in the dining room (salmon). There's was much conversation. At my table the most interesting debates were about sex and race with Andrew Roger and Ford Doolottle.

And so endeth the first day.

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