Basics: Synteny

Let’s play the most boring card game in the universe!

Here are the rules. We start with a fully sorted deck of 52 cards, and we deal out four hands. We don’t deal in the ordinary way, either: we give the top 13 cards to the first player, then the next 13 to the second, and so forth. (We could also do the usual deal, but it makes the illustration and logic a little more difficult to see. We’ll keep it simple for now.)

This is what the table will look like.

Hand 1 Ai-233f23e2a2ca8059264849e39e1760d2-heart.gif Ki-233f23e2a2ca8059264849e39e1760d2-heart.gif Qi-233f23e2a2ca8059264849e39e1760d2-heart.gif Ji-233f23e2a2ca8059264849e39e1760d2-heart.gif 10i-233f23e2a2ca8059264849e39e1760d2-heart.gif 9i-233f23e2a2ca8059264849e39e1760d2-heart.gif 8i-233f23e2a2ca8059264849e39e1760d2-heart.gif 7i-233f23e2a2ca8059264849e39e1760d2-heart.gif 6i-233f23e2a2ca8059264849e39e1760d2-heart.gif 5i-233f23e2a2ca8059264849e39e1760d2-heart.gif 4i-233f23e2a2ca8059264849e39e1760d2-heart.gif 3i-233f23e2a2ca8059264849e39e1760d2-heart.gif 2i-233f23e2a2ca8059264849e39e1760d2-heart.gif
Hand 2 Ai-94f8cf214b78029e2cd1e9398229dda0-club.gif Ki-94f8cf214b78029e2cd1e9398229dda0-club.gif Qi-94f8cf214b78029e2cd1e9398229dda0-club.gif Ji-94f8cf214b78029e2cd1e9398229dda0-club.gif 10i-94f8cf214b78029e2cd1e9398229dda0-club.gif 9i-94f8cf214b78029e2cd1e9398229dda0-club.gif 8i-94f8cf214b78029e2cd1e9398229dda0-club.gif 7i-94f8cf214b78029e2cd1e9398229dda0-club.gif 6i-94f8cf214b78029e2cd1e9398229dda0-club.gif 5i-94f8cf214b78029e2cd1e9398229dda0-club.gif 4i-94f8cf214b78029e2cd1e9398229dda0-club.gif 3i-94f8cf214b78029e2cd1e9398229dda0-club.gif 2i-94f8cf214b78029e2cd1e9398229dda0-club.gif
Hand 3 Ai-2b47b78b9878c3d3b29bd4f7d2d03e19-diamond.gif Ki-2b47b78b9878c3d3b29bd4f7d2d03e19-diamond.gif Qi-2b47b78b9878c3d3b29bd4f7d2d03e19-diamond.gif Ji-2b47b78b9878c3d3b29bd4f7d2d03e19-diamond.gif 10i-2b47b78b9878c3d3b29bd4f7d2d03e19-diamond.gif 9i-2b47b78b9878c3d3b29bd4f7d2d03e19-diamond.gif 8i-2b47b78b9878c3d3b29bd4f7d2d03e19-diamond.gif 7i-2b47b78b9878c3d3b29bd4f7d2d03e19-diamond.gif 6i-2b47b78b9878c3d3b29bd4f7d2d03e19-diamond.gif 5i-2b47b78b9878c3d3b29bd4f7d2d03e19-diamond.gif 4i-2b47b78b9878c3d3b29bd4f7d2d03e19-diamond.gif 3i-2b47b78b9878c3d3b29bd4f7d2d03e19-diamond.gif 2i-2b47b78b9878c3d3b29bd4f7d2d03e19-diamond.gif
Hand 4 Ai-37cc42c4042ea4372806e327e67b2e42-spade.gif Ki-37cc42c4042ea4372806e327e67b2e42-spade.gif Qi-37cc42c4042ea4372806e327e67b2e42-spade.gif Ji-37cc42c4042ea4372806e327e67b2e42-spade.gif 10i-37cc42c4042ea4372806e327e67b2e42-spade.gif 9i-37cc42c4042ea4372806e327e67b2e42-spade.gif 8i-37cc42c4042ea4372806e327e67b2e42-spade.gif 7i-37cc42c4042ea4372806e327e67b2e42-spade.gif 6i-37cc42c4042ea4372806e327e67b2e42-spade.gif 5i-37cc42c4042ea4372806e327e67b2e42-spade.gif 4i-37cc42c4042ea4372806e327e67b2e42-spade.gif 3i-37cc42c4042ea4372806e327e67b2e42-spade.gif 2i-37cc42c4042ea4372806e327e67b2e42-spade.gif

Next, we play the game, whatever it is. It really doesn’t matter, since we know exactly what hand everyone has, right? So don’t worry about the rules for that. What’s important is that next the dealer carefully picks up each hand in reverse order and stacks them, restoring the original arrangement of the deck.

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Hubris, gall, arrogance…inanity

Would you believe that Andy Schlafly, head kook at Conservapædia, wrote a letter to Richard Lenski, demanding release of his data to Schlafly and his crack team of home-schooled children? Schlafly is a creationist and ideologue of the worst sort; he has no qualifications in biology, and only wants the data because he doesn’t believe it, and would no doubt then use his vast powers of incomprehension to garble it.

That isn’t noteworthy, though. We expect creationists to act like indignant idiots when the facts are shown to them. What’s really cool is that Lenski wrote back.

Dear Mr. Schlafly:

I suggest you might want to read our paper itself, which is available for download at most university libraries and is also posted as publication #180 on my website. Here’s a brief summary that addresses your three points.

1) “… your claims, that E. Coli bacteria had an evolutionary beneficial mutation in your study.” We (my group and scientific collaborators) have already published several papers that document beneficial mutations in our long-term experiment. These papers provide exact details on the identity of the mutations, as well as genetic constructions where we have produced genotypes that differ by single mutations, then compete them, demonstrating that the mutations confer an advantage under the environmental conditions of the experiment. See papers # 122, 140, 155, 166, and 178 referenced on my website. In the latest paper, you will see that we make no claim to having identified the genetic basis of the mutations observed in this study. However, we have found a number of mutant clones that have heritable differences in behavior (growth on citrate), and which confer a clear advantage in the environment where they evolved, which contains citrate. Our future work will seek to identify the responsible mutations.

2. “Specifically, we wonder about the data supporting your claim that one of your colonies of E. Coli developed the ability to absorb citrate, something not found in wild E. Coli, at around 31,500 generations.” You will find all the relevant methods and data supporting this claim in our paper. We also establish in our paper, through various phenotypic and genetic markers, that the Cit+ mutant was indeed a descendant of the original strain used in our experiments.

3. “In addition, there is skepticism that 3 new and useful proteins appeared in the colony around generation 20,000.” We make no such claim anywhere in our paper, nor do I think it is correct. Proteins do not “appear out of the blue”, in any case. We do show that what we call a “potentiated” genotype had evolved by generation 20,000 that had a greater propensity to produce Cit+ mutants. We also show that the dynamics of appearance of Cit+ mutants in the potentiated genotypes are highly suggestive of the requirement for two additional mutations to yield the resulting Cit+ trait. Moreover, we found that Cit+ mutants, when they first appeared, were often rather weak at using citrate. At least the main Cit+ line that we studied underwent an additional mutation (or mutations) that refined that ability and led to a large improvement in growth on citrate. All these issues and the supporting methods and data are covered in our paper.

Sincerely,

Richard Lenski

Wow. That was far more polite than they deserve, but good for Dr Lenski. Unfortunately, Schlafly will now use the reply as an opportunity to smugly regard himself as a serious player, and he will also ignore the substance to continue to deny that evolution occurred. But maybe, just maybe, someone in the collection of deprived children subjected to Schlafly’s tutelage will notice that real scientists can give substantial replies to his usual ignorant nonsense.

How Life Began

As I said I would, I’m watching this History Channel documentary about the origin of life. How about a little live-blogging?

8:00. Ugh. It begins with a bunch of tripe from Coyne and Polkinghorne, claiming we need religion to understand the meaning of life. This is a bad, bad start, but I’m hoping it’s nothing but a weasely preliminary that they will then abandon to get to some real science.

There are lots of gimmicky special efects, but OK, let’s get the general audience interested. I’m not too keen on the parade of talking heads, though: they keep trotting out different investigators, letting them say a sentence or two, and then zipping off elsewhere. I know you don’t want some guy sitting and droning at you, but this seems like a poor compromise.


8:15. It’s a quick tour of the complexity of the cell. They’re using this special effects analogy of a “factory of life” where chemistry is going on.

First important element of life: metabolism. Second: life is cellular, with compartments. Third: life can replicate.

Now we get a parts catalog of polymers: lipids, proteins, and nucleic acids.

Very weird: in their factory analogy, they point to something hidden behind a big red curtain and say that that’s where all these bits and pieces come together to make something that’s alive; it seems a bit of a cop-out, a way to pretend there’s something hidden where the viewer can imagine anything they want. Come on, bite the bullet and admit it: life is chemistry, and there is nothing more.

Now we get a fairly lengthy discussion of the idea of emergence. At least they clearly state that emergence is nothing magical, but is just a consequence of the execution of the laws of nature. This is a rather pointless digression, I think.

OK, now we get a timeline of the origin of life: it appeared about 3.8 billion years ago, on a very hostile planet with no oxygen in the air, and just cooling after the last of the great meteor bombardments. This leads naturally into a discussion of extremophiles, with a tour of Mono Lake.

Segue to commercial by mentioning that life will change the environment of the earth.


8:30. Conditions on early life are hostile to us, but chemical energy is abundant. Life would have existed as single-celled forms only, which may have been unrecognizable to us (why are they showing video micrographs of nematodes while they tell us this?)

Stromatolites are introduced, as organisms that grew on chemical energy sources. What are those energy sources?

The camera crew goes spelunking. They’re collecting rock-eating microbes, which the scientists argue is a kind of primitive chemistry that evolved before photosynthesis.

Nice reminder that single-celled life was the only form of life here for 80% of the history of earth, but then they make the mistake of using the past tense in saying they were the dominant form of life on the planet.

Wait…now they’re saying that the ability to reproduce is a property of DNA? That’s kind of cutting off the possibility of an interesting discussion of alternative paths.

Suddenly, boom, they’re talking about Leeuwenhoek. Hang on, this is a bit jumpy. Can we talk more about extremophile chemistry before we start on 17th-18th century microscopy?

Now it’s all about photosynthesis. We’ve moved way, way beyond the period of early abiogenesis already, and they’ve scarcely touched on any of the major theories.

Before the commercial, we get talk about multicellularity and oxygen chemistry. Either they’re going to be jumping about an awful lot and scrambling the story, or we’re not going to get anything about abiogenic chemistry…


8:45. Oops, I had to miss part of this section to run some real-world errands. I come back to see the Burgess Shale and a discussion of the Cambrian explosion. This is long, long after the origin of life!

It’s an excuse to show some computer animations of Anomalocaris, anyway.

George Coyne does a good job now saying that life doesn’t need a designer; Polkinghorne pops up to make excuses for the metaphorical nature of the book of Genesis. Bugger off, Polkinghorne, you bother me, ya twit.

Now we get a summary of the importance of selection and sex. I don’t think we’re going to get a good review of biogenesis anymore — sex is not an important issue in that field.

I am completely baffled. Before the commercial, they say the big question was how human life arose…then they ask, “What was the specific mechanism that caused non-living chemistry into living biology?” Weird. These are very different questions. They seem to be muddling up the origins of life with the origins of the only important form of life, humans.


9:00. We’re back to animals. Come on, animals are peculiar latecomers.

Maybe it’s an excuse to return to a historical survey of ideas about the origin of life. I hope.

Aristotle proposes the idea of spontaneous generation, an idea that hangs on for centuries but is relatively easy to disprove…as Redi and Spallanzani do. This stuff isn’t bad, but it feels like introductory material they should have brought up at the beginning.

Actually, I’m enjoying this part best of all so far. They’re actually talking about the experiments done to disprove spontaneous generation, so it’s a useful summary of how scientists actually do science.

Our closing question: so how did life arise from chemistry? The second half is off to a good start, I think.


9:15. I’ve got to say…the actor playing Charles Darwin looks nothing like him, and that beard looks cheesy and fake.

We get the early concepts: “warm little pond”, “primorial soup”. There the questions are about what kind of chemicals and conditions existed at the beginning of life. They mention Oparin’s ideas about the chemical monomers available, and the idea that these chemicals would accumulate in the oceans. It seems like a very low probability sort of exercise.

The Miller/Urey experiment at last. This is well done, with a very nice illustration of the apparatus and techniques. They get it right, too — it was nice work that showed that the natural chemistry that would produce organic substrates for life was relatively trivial. It also set up unrealistic expectations for how easy it would be to create life.

Closing premise: now there is a race to figure out prebiotic chemistry.


9:30. Let’s consider other sources of organic matter!

Space-borne debris. Complex organic molecules are found in metorites and in space. We get to see scientists extracting organic molecules from ground-up meteorites. Panspermia is mentioned, but they aren’t doing a good job of distinguishing chemicals from life. At least Bob Hazen is razor sharp in pointing out that panspermia is a cop out.

Hazen also clearly explains bottom-up (exploring basic principles about biochemistry to replicate the events at the origin) vs. top-down (working in reverse from extant life backwards to the origin). He also explains that we need a multiplicity of approaches, and the origin may also have been generated from diverse sources.

Hmm. Commercials seem to be coming more frequently as we get close to the end.


9:40. It’s deep-sea vent time, with nice shots of black smokers and squid. Then Bob Hazen shows us how his experiments on the chemistry at high pressure and temperature are done. Cooking a little pyruvate for a while generates substances that form micelles.

Clays! Clays are shown as potential catalytic surfaces that would concentrate organic compounds and promote reactions that form, for instance, RNA. RNA monomers will polymerize in the presence of clays.

Transition: are scientists on the verge of creating artificial life in the lab?


9:50. It’s “3000 years after Aristotle”? What?

Never mind. Now we get pretty crystals growing and changing. This bit is a little fluffy.

All right: Jack Szostak. They describe his efforts to try and create a protocell. Cool video of creating cell membranes — beautiful little droplets bubbling out of an electrode. Some good cautionary statements: if they succeed, this will still only be a model, not a demonstration of how it actually happened 3.8 billion years ago.

They don’t really say much about the mechanisms in the closing minutes, but they do have a nice statement by Neil de Grasse Tyson about how the search is the important thing, even if we don’t get an answer.


Summary: the first hour was a muddle, and not worth watching. If you’re going to catch it later, just watch the second half.

The last half wasn’t bad. It at least talked very briefly about the actual science and how it is done. It was all painfully abbreviated and only touched lightly on the subject, but I think that is simply a limitation of the medium. I imagine it’s a seriously difficult balancing act to try and meet the needs of real nerds (like us!) and the more casual viewer, so I’ll accept the compromise.

Something at the end to lead the interested viewer to more in-depth sources would have been a good idea — they could have at least mentioned Hazen’s Genesis as a plug.

Historical contingency in the evolution of E. coli

Blogging on Peer-Reviewed Research

While I was traveling last week, an important paper came out on evolution in E. coli, describing the work of Blount, Borland, and Lenski on the appearance of novel traits in an experimental population of bacteria. I thought everyone would have covered this story by the time I got back, but there hasn’t been a lot of information in the blogosphere yet. Some of the stories get the emphasis wrong, claiming that this is all about the rapid acquisition of complex traits, while the creationists are making a complete hash of the story. Carl Zimmer gets it right, of course, and he has the advantage of having just published a book(amzn/b&n/abe/pwll) on the subject, with some excellent discussion of Lenski’s work.

The key phrase is right there at the beginning of the title: historical contingency. This paper is all about how accidents in the genetics of a population can shape its future evolutionary trajectory. It is describing how a new capability that requires some complex novelties can evolve, and it is saying plainly that in this case it is not by the fortuitous simultaneous appearance of a set of mutations, but is conditional on the genetic background of the population. That is, two populations may be roughly equivalent in fitness and phenotype, but the presence of (probably) neutral mutations in one may enable other changes that predispose it to particular patterns of change.

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How do you make a cephalopod drool?

Blogging on Peer-Reviewed Research

We’re all familiar with Pavlov’s conditioning experiments with dogs. Dogs were treated to an unconditioned stimulus — something to which they would normally respond with a specific behavior, in this case, meat juice which would cause them to drool. Then they were simultaneously exposed to the unconditioned stimulus and a new stimulus, the conditioned stimulus, that they would learn to associate with the tasty, drool-worthy stimulus — a bell. Afterwards, ringing a bell alone would cause the dogs to make the drooling response. The ability to make such an association is a measure of the learning ability of the animal.

Now…how do we carry out such an experiment on a cephalopod? And can it be done on a cephalopod with a reputation (perhaps undeserved, as we shall see) as a more primitive, less intelligent member of the clade?

The nautilus, Nautilus pompilius despite being a beautiful animal in its own right, is generally regarded as the simplest of the cephalopods, with a small brain lacking the more specialized areas associated with learning and memory. It’s a relatively slow moving beast, drifting up and down through the water column to forage for food. It has primitive eyes, which to visual animals like ourselves seems to be a mark of less sophisticated sensory processing, but it has an elaborate array of tentacles and rhinophores which it uses to probe for food by touch and smell/taste. Compared to big-eyed, swift squid, a nautilus just seems a little sluggish and slow.

So let’s look and see how good a nautilus’s memory might be. First, we need a response to stimuli that we can recognize and measure, equivalent to the drooling of Pavlov’s dogs. While they don’t measurably salivate, the nautilus does have a reaction to the hint of something tasty in the water — it will extend its tentacles and rhinophores, as seen below, in a quantifiable metric called the tentacle extension response, or TER.

i-7be37621e667c883026d43ae4fe35d87-naut_behav.jpg
The scoring system for tentacle extension response (TER) in chambered nautilus. TER was graded every 5 s from a minimum score of 0 to a
maximum score of 3. Each level corresponds to a range of percentage extension relative to the length of the animalʼs hood. Zero is recorded when all
tentacles are retracted into their sheaths. A score of 1 corresponds to an extension of <33% of the hood length. A score of 2 corresponds to extension
between 34% and 66%, and 3 is given when tentacles are extended beyond 67% of hood length.

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Frontiers in cell biology

Alex Palazzo is talking about open questions in cell biology — in this case, control of organelle shape. Any of us who have poked around in cells know that it is not an amorphous blob of goo, but has characteristic, recognizable elements that we can see from cell to cell. What confers these stereotypic intracellular morphologies on organelles, and what are the functional consequences, if any?

(There are no jebons in there, so you don’t get to use those in your answer.)

Materpiscis attenboroughi

Blogging on Peer-Reviewed Research

It’s not often that something as delicate as details of the reproductive tract get preserved, but here’s a phenomenal fossil of a Devonian placoderm containing the fragile bones of an embryo inside, along with the tracery of an umbilical cord and yolk sac.

This is cool: it says that true viviparity, something more than just retention of an egg internally, but also the formation of specialized maternal/embryonic structures, is at least 380 million years old. Hooray for motherhood!

Here’s a reconstruction of what the animal would have looked like in life, as it is giving birth to its young.

i-30bbeb003e04870f189ebaceaad2bd5b-materpiscis_recon.jpg
a, Diagram showing position of embryo and yolk sac within the mother. b, Artist’s reconstruction of Materpiscis gen. nov. giving birth.

Long JA, Trinajstic K, Young GC, Senden T (2008) Live birth in the Devonian period. Nature 453:650-652.

IEDG2008: Model systems are dead, long live model systems

I’ve discovered a couple of important things at this meeting.

One, late night sessions at west coast meetings are deadly for any of us coming from more eastern time zones. At least the morning sessions are low stress.

Two, I haven’t heard one Drosophila talk yet, and the message is clear: we’re now in the stage of evo-devo in which everyone is diversifying and chasing down a wide array of species. There was a bit of model-system bashing, but at the same time, everyone is acknowledging the crucial role of those traditional, but weird and derived, lab critters in providing a point of comparison and being the source of many of the tools being used to explore phylogeny now. I thought, though, that the smartest comment of the evening was that now everything is a model system.

I’ve got some dense piles of notes on the evening session, but I’m going to give you the short version of everything, with an emphasis on the novel twists.

Michael Akam talked about segmentation genes, which every developmental zoologist now knows inside and out — trust me, this is a familiar topic with over 25 years of detailed research … in Drosophila. Akam made the point that now it’s looking clear that three of the major segmented phyla, the arthropods, annelids, and chordates, may be using related genes to accomplish segmentation, but they seem to be using different mechanisms — so he considers the question of whether segmentation in these three is homologous is still an open question. He also discussed recent work on the centipede Strigamia (definitely not a lab animal: they can’t breed them in the lab yet, so all the work is done by collecting embryos in the field, in Scotland). They have a dynamic pattern of segment addition that is very different from what you find in flies, and more similar in some ways to chodate segmentation.

Chelsea Specht talked about floral evolution in the Zingiberales. I’m an animal guy, so even the most basic stuff in this talk was entirely new to me. I know the general rules of the spatial development of in the fruit fly of the plant world, Arabidopsis, and she gave us a bit of context there, reminding us of the concentric development of sepals, petals, stamens, and carpels. The Zingiberales are a large and diverse group of plants that includes bananas and ginger, and one characteristic is an extravagant modification of the canonical pattern, with extra stamens, a loss of select stamens, and a fusion of stamens to form a novel structure, the labellum, which in these plants functionally replaces the petals. So of course they’re looking into the genes involved in the patterns, which turn out to be the familiar Arabidopsis genes redeployed in new patterns.

Paul Sereno had a talk that took a very different tack, and was unfortunately giving it at the equivalent of 11:00pm Minnesota time, so I’m sorry to say I didn’t follow it carefully. He was discussing the analysis of morphology, and was advocating the development of tools and techniques to compare data sets in addition to the usual output, phylogenetic trees. He was making the case that a lot of morphological studies are actually very poor (a creationist in the audience would have loved it, largely because he wouldn’t have understood the context) because the input data sets of different studies are not comparable.

And now I have to get back to work and listen to the next set of talks.