Q: What unique organ is found only in mammals, but not in fish, amphibians, reptiles, or birds?
The title and that little picture to the left ought to be hint enough, but if not, read on.
There’s an important phenomenon in development called neurulation. This is a process that starts with a flat sheet of ectodermal cells, folds them into a tube, and creates our dorsal nervous system. Here’s a simple cross-section of the process in a salamander, but in general outline we humans do pretty much the same thing. Cells move up and inward, and then zipper together along the length of the animal to produce a closed tube.
It’s a seemingly simple event with a great deal of underlying complexity. It requires coordinated changes in the shape of ectodermal cells to drive the changes in tissue shape, and invisible in simple diagrams to the right are all the inductive interactions going on that trigger the differentiation of the tube into a nervous system.
If you’ve seen BladeRunner, you know the short soliloquy at the end by one of the android replicants, Roy, as he’s about to expire from a genetically programmed early death.
“I’ve seen things you people wouldn’t believe. Attack ships on fire off the shoulder of Orion. I watched c-beams…glitter in the dark near Tanhauser Gate. All those…moments will be lost…in time, like tears…in rain. Time…to die.”
There’s an interesting idea here, that death can be an intrinsic property of our existence, a kind of internal mortality clock that is always ticking away, and eventually our time will run out and clunk, we’ll drop dead. There is a germ of truth to it; there are genetic factors that may predispose one to greater longevity, and in the nematode worm C. elegans there are known mutants that can greatly extend the lifetime of the animal under laboratory conditions.
However, in humans only about 25% of the variation in life span can be ascribed to genetic factors to any degree, and even in lab animals where variables can be greatly reduced, only 10-40% of the life span variation has a genetic component. There is a huge amount of chance involved; after all, there aren’t likely to be any genes that give you resistance to being run over by a bus. Life is like a long dice game, and while starting with a good endowment might let you keep playing for a longer time, eventually everyone craps out, and a run of bad luck can wipe out even the richest starting position rapidly.
In between these extremes of genetic predetermination and pure luck, though, a recent paper in Nature Genetics finds another possibility: factors in the organism that are not heritable, yet from an early age can be reasonably good predictors of mortality.
Everyone can stop now, my brain is full. Seriously, this is a painful meeting: my usual strategy at science meetings is to be picky and see just a few talks in a few sessions, to avoid burnout…but at this one, I go to one session and sit through the whole thing, and at the breaks I look at the program and moan over the concurrent sessions I have to be missing. I have to come to SICB more often, that’s for sure.
I do have one major complaint, though: PowerPoint abuse. The evolution of slides has continued apace since my graduate school days, when one slide was one photograph, developed in a darkroom ourselves, and then carefully labeled with letraset lettering, photographed again on a copy stand with slide film, and then sent off for processing (usually the day before the meeting, so there was no slack for redoing anything.) Now the slides are all huge multipaneled affairs with data packed into tiny little boxes that fade in as the speaker does a tarantella on the keyboard, and it’s getting a little irritating. Most of the talks this morning would, at some point, throw up a gigantic, intricately detailed cladogram with 50 taxa and branch points all labeled and circles and arrows and scary tiny lettering all around. Any one slide legitimately represents something that the speaker could talk about for an hour, no problem, but wham-bam-zoom, they’ll run through 20 of them in 20 minutes. If the information density is going to be this high, they ought to set it up so they can beam these monster slides to our laptops over the wireless network, so we can actually try to absorb it into our heads in some way other than being battered about the cranium with it.
I spent Friday morning at the Key Transitions in Animal Evolution symposium.
F. Boero: Cnidarian milestones in metazoan evolution. This talk was a bit thin on the data, but it was presented more as a conceptual overview, so I let it go. The idea was simple: it was an anti-Great Chain of Being talk, pointing out that sponges and especially cnidarians were darned important creatures that ought to be appreciated for the fact that they bear the seeds of everything we consider especially essential to the bilateria. They have bilateral symmetry, many have supporting skeletons, polyp buds have an internal mass that corresponds in many ways to mesoderm, they have body cavities, the modularity of their development has affinities to bilaterian metamery, and most interestingly, cnidarian planula larvae have specialized concentrations of nerve cells that resemble a brain. One weird twist (I love weird twists) was the idea that the cnidocyst was such an incredibly potent adaptation that the cnidaria didn’t need all the elaborate complexity of the bilateria to succeed, and that maybe an important milestone that was a precursor to our evolution was the loss of cnidocysts.
B. F. Lang: The evolutionary transition from protists to Metazoa: mitochondrial genome organization and phylogenomic analyses based on nuclear and mitochondrial genes. I was rather far over my head in this talk; it was hardcore phylogenetic analysis of really distant branch points in our evolutionary history—this fellow is trying to puzzle out the branch point between fungi and animals. I mainly just jotted down a few names I’ll have to look up later: the Ichthyosporia, which are fungal-like cells with amoeboid stages, the Nuclearia, which are low on the branch leading to the fungi, the Capsaspora, which similarly lie on a branch leading to the animals, and the Apusozoa, bikont flagellates that have been poorly characterized so far.
D.K. Jacobs: Origins of sensory and neural organization in basal metazoa. The cnidarian fan club was out in force in this session. This was a talk on the identification of cnidarian genes usually associated with nervous system and sensory organ development and function, the point being that all of the precursors to our rather more elaborate neural processing system are there in jellyfish. There were a few places where I wondered if he was going a little too far—there’s no reason to assume that finding a gene that is used in the vertebrate brain in a cnidarian means that gene has a similar function there—but still an interesting talk. One cute idea was that the choanocytes of sponges can also be thought of as sensory organs, and also that neural genes seem to share functions with nephridia/kidneys, too, raising the possibility of a primitive link between excretion and the origins of the nervous system. (Watch Fox News, and this possibility will seem even more likely).
G. Wagner: Do genome duplications play a role in key transitions? This is the second time I’ve heard this Wagner fellow talk, and he keeps making me think. He brought up a familiar correlation: in vertebrate evolution, we see signs that there are major gene duplications at the same time that we see major radiations. In the vertebrate lineage, for instance, we see two whole genome duplications, and the conceit is that these increases in genetic material provided the substrate for more sophisticated developmental events that were the source of our success; similarly, the even more successful teleosts show signs of a third round of duplications. Wagner objected, pointing out that there are many highly successful groups that did not exhibit these duplications (arthropods, insect, mammals, and birds, for instance), and that others, such as plants and sturgeon, have duplications but no subsequent radiation. He argued that it was an artifact, not evidence of a causal relationship. The rapid expansion of a lineage during an adaptive radiation would act to preserve and propagate any genetic quirks of the founding population. The duplications are neither necessary nor sufficient to instigate a key transition. One point that came up very briefly in the Q&A was that we developmental biologists are a bit obsessive about regulatory genes like the Hox genes and think those are indicative of importance, but that there are also duplications in, for instance, the glyocolytic enzymes that also correspond to the major transitions.
N.W. Blackstone: Foods-eye view of the transition from basal metazoans to bilaterians. This was another weird talk that came from a completely different perspective and made me think. It might actually be a little too weird, but it’s still provocative and interesting. Blackstone is looking at everything from the perspective of metabolic signaling—he’s clearly one of those crazy people coming out of the bacterial tradition. Cells communicate with one another with the byproducts of metabolism, where the redox state of membrane proteins are read as indicators of the internal state of the cells (he later calls this “honest signaling”, because there aren’t any intermediates between the cell and the expression of its metabolic state). The big innovation in the eukaryotes was to escape volume constraints by folding their chemiosmotic membranes into the interior of the organism, and the major animal innovation was the evolution of the mouth, which allowed specialized acquisition and processing of food patches. Subsequent evolution was to allow the animal to sense and seek out and exploit food patches in an environment where they were dispersed in a non-uniform manner. Another interesting tangent was the question of cancer: long-lived sponges and cnidarians don’t get cancer. His explanation was that it was because their cells use that “honest” metabolic signaling, so that rogue cells don’t have a way to trick the organism into allowing them to use more resources than they actually need; the only way to signal is to exhibit genuine metabolic distress, and cells with metabolic problems will die. Our cells have these indirect, multi-layered signaling mechanisms that allow cancer cells to “lie” to the organism as a whole.
P. Cartwright: Rocks and clocks: integrating fossils and molecules to date transitions in early animal evolution. Molecular phylogeny is a useful tool to find patterns, and recognize branch points; this information needs to be integrated with fossil date to calibrate the clock and anchor those events to specific dates. This work was a combined effort to put together a catalog of 18s and 28s trees, and use fossil evidence to constrain the timing of the events in a metazoan cladogram. I wasn’t entirely convinced that they’d overcome the obvious problems—fossils can provide a minimum but not a maximum age—but as an excuse to show lots of pictures of Cambrian and pre-Cambrian fossils, I wasn’t going to complain. In particular, they had some amazing cnidarian fossils from 500 million year old rocks in Utah that were pretty much indistinguishable from modern taxa; jellyfish definitely are in a good niche. In her final table of conclusions (which flew by much too quickly!), she pinned the origin of the metazoa to 950mya, the deuterostomes to 539mya, the lophotrochozoa to 537mya, the ecdysozoa to 541mya, and the placozoa to 61mya (!). The clustering of those significant groups to right around the Cambrian was an indication that the Cambrian explosion was real.
M. Q. Martindale: The developmental basis of body plan organization in the Eumetazoa. Uh, Mark can talk really, really fast. My notes are a rather unreadable scrawl as I tried to keep up. A general point: he emphasized that much of what we can expect to see from developmental biologists is going to look like the intricate ‘circuit diagrams’ that Eric Davidson has published, where the fundamental unit is a network of gene interactions that define a cell state. He showed Davidson’s endomesoderm specification kernel for echinoderms, for instance, and then went through each of the genes involved and showed that they are all also present in Nematostella, and that they are almost all involved in endomesoderm specification there, as well. While the network has not been identified in the cnidarian, only the components, I do’t think we’ll be too surprised to see similar interactions appear as the details are worked out.
D.J. Miller: Implications of cnidarian gene expression data for the origins of bilaterality: is the glass half full or half empty. Where Martindale was all about the similarities, Miller was all about the differences. He’s working with a cnidarian, too, but a different one, Acropora. He was also explaining the expression of important early patterning genes, but one very interesting difference is that he looked at Emx and Otx, homologs to anterior-posterior genes in the bilateria that are expressed in the anterior end of those animals—but are expressed at opposite ends of the Acropora planula from each other. While some gene functions are conserved, there is no simple correspondence along the body axis.
J. Extavour: Urbilaterian reproduction. A different sort of talk: this one was about the nature of Urbilaterian germ cells. She made the case that one of the key steps necessary to the evolution of true multicellularity was the sequestration of a distinct stem cell population that was specialized to minimize mutation with a greatly reduced mitotic rate, reduced transcription, and with mechanisms to reduce the activity of transposable elements. This was part of the process of making the fitness of individual cells take a backseat to the overall fitness of the organism.
P.W.H. Holland: More than one way to make a worm. This talk was fun. He started with the idea of the worm, a flexible, elongated, motile tube, and showed that “worm” was a successful form that one could find scattered across the phyla of the bilateria, and that the urbilaterian was almost certainly a worm. He then raised two questions: are there examples of more derived forms that have secondarily given up features to revert to “wormness” (he gave one example, arguing that the hagfish was basically a chordate worm); and more interestingly, are there any examples of organisms that have independently evolved into a worm? He then showed us a movie of a creature that definitely looked like a worm; on first sight, it looked like a nematode, but rather than undulating and crawling it did a strange corkscrew curl. It’s called Buddenbrockia, and it’s a parasite found inside bryozoans. closer examination showed that it is a sealed hollow tube, completely mouthless and without a gut, and with no sensory organs, and that its interior is lined with 4 blocks of longitudinal muscle. It looked like something from outer space, if you asked me. Inside that tube, though, can be found flagellated spores that look like myxozoans. Molecular phylogeny reveals that it is a myxozoan, and that it is nested within the cnidaria. The idea is that this wormlike animal was built by breaking down a cnidarian and building it up again, and so represents a worm that has evolved independently of the Eubilateria—a worm is apparently a kind of universally basic form to take. Very cool!
Here’s what I heard this morning. Wonderful stuff, all of it, and I’m having a grand time. This is a quick summary, and now I have to rush back to the meeting for more.
S. Kuratani: Craniofacial evolution from a developmental perspective. This was a lamprey and hagfish talk, comparing them to vertebrates. Hox gene expression patterns in lamprey, which assign anterior-posterior positional information, are very similar to those in vertebrates, but there is no temporal colinearity—timing is all over the place. There is no apparent dorsal-ventral patterning of Dlx gene expresion. They’ve collected a small number of hagfish eggs and embryos and gotten good histology (unlike much of the older work). The neural crest forms by delamination and migrates into the intersegmental spaces; it also looks very much like the vertebrate pattern.
A. Abzhanov: Pecking at the origin of avian morphological variation. This was the story recently published in Nature on the molecular basis of beak shapes in the Galapagos finches. In short, Bmp4 expression is important in regulating the width and depth of the beak, and Calmodulin expression affects the length; there is modularity in controlling the different beak dimensions. He promises to look in the future at a couple of different phenomena: a finch with a deep but narrow beak might help sort out the factors involved in those two dimensions, he’s examining Galapagos mockingbirds, and he’s looking at muscle-bone coupling, since muscles have to follow changes in bone structure.
J. Helms: Unraveling the basis for species specific facial form. More birds! Here the question is the role of differences in neural crest potential that affect beak/face morphology. In some cool transplant experiments, she put neural crest from a duck embryo (long, flat bill) into a quail (short, pointy beak), and found that the quail embryos from flatter, broader bills. The converse experiment, quail neural crest into a duck embryo, produced duck embryos with short, pointed beaks. Microarray analysis of the genes with differential patterns of expression in these two species revealed that the gene differences were turned on at the phylotypic stage, when the facial prominences were indistinguishable, and the gene expression patterns at the phenotypic stage were simply maintained or held over — there is a hidden variation at the phylotypic stage that precedes the morphological differentiation. She also showed some promising work for the future, looking at the molecular basis for beak variation in different breeds of pigeons.
Y. Yamamoto: Why cavefish lost their eyes? Natural selection or neutral theory. Hey, get the latest issue of Seed — I summarized this story already! Even shorter summary: it’s indirect selection for a pleiotropic tradeoff.
G. Schlosser: How old genes make a new head: recent insights into development and evolution of neural crest and placodes in vertebrates. This is a neat little story about structural innovations in the evolution of the head. In addition to brain and ectoderm in the head, you’ve got two other in-between populations of plastic and critical cells: the neural crest, migratory cells that contribute to a host of tissues, and placodes, or ectodermal thickenings, that form structures like ears, lenses, lateral lines (if you had a lateral line), etc. Both populations arise at the neural plate boundary. One evolutionary scenario is that the boundary population appeared first, and then later subsets specialized to form neural crest and placodes; this model emphasizes a common origin for both. Schlosser presented his evidence and argument that they were unique from the beginning: placods are derived from the ectodermal side of the boundary, while neural crest are from the neural side.
L.Z. Holland: Heads or tails? Amphioxus and the evolution of axial patterning in chordates. This was a very thorough summary of comparative patterns of early gene expression in Amphioxus and frogs, fish, and all those other excessively complicated derived forms. She made the case that in many ways Amphioxius is a basal chordate. and that it has great advantages for studying axis formation and gastrulation: cell movements are minimal and simple, and you can see gene expression domains untangled from all the smearing of the extensive cell movements we see in, for instance, a frog. Among the interesting conclusions are the idea that differential Wnt gene expression is instrumental in specifying the anterior and posterior ends of the animal, and that gradients of retinoic acid (which directly target Hox gene expression) sets up positional information along the A/P axis in between.
G.P. Wagner: Linking the evolution of genes with the evolution of morphological characters. This was the first of two talks that set a different tone. Wagner pointed out that the developmental approach favored so far is excellent for sorting out what genes affect what other genes and are associated with the morphological differences that arise during development, but that they don’t tell you what the molecular correlates of those differences are: what specifically are the sequence changes in the sonic hedgehog gene or its regulators that cause expansion of its domain in blind cavefish? He argued that evolutionary genetics can identify candidate molecular differences as part of a program of working out the precise details of evolutionary/developmental change. Readers of Carroll’s work and its emphasis on the importance of cis regulatory elements will be interested that Wagner goes the other way, and is much more interested in the evolution of transcription factors. He gave a couple of reasons: 1) the specificity of gene regulation arises from protein-protein interactions in regulatory complexes. While there is much emphasis on the conserved sites that bind DNA in an individual protein, that is a small part of the whole, and these proteins are often poorly conserved out in the 80% that doesn’t stick to DNA, but contacts other proteins. 2) Changes in these proteins change functionality in the organims in evolution. 3) There is evidence of directional selectivity in transcription factors. 4) It’s much easier to work with sequences that are actually expressed (ah, pragmatism!). In detail, he discussed the Hoxa13 gene in zebrafish, which has been duplicated again in teleosts into Hoxa13a and Hoxa13b forms. The Hoxa13a gene is associated with a quirky morphological feature of the cypriniform fish that we zebrafish people are familiar with, the caudal extension of the yolk sac. It’s an easily assayed feature, and Wagner showed that morpholino knockdowns of Hoxa13a cleanly suppressed yolk sac extension.
Lark G: Links between the genetic architecture and functional morphology of the canid skeleton. This talk was a radical break from the previous ones, and was almost purely genetics. I confess, I was starving and worn out and had to make a break for lunch, so I didn’t give this talk the attention it deserved or needed, but I’ll be looking into it later. Lark is looking at quantitative trait loci in Portuguese Water Dogs and the Red Fox, and arguing that there are conserved patterns of variability that have survived 10 million years of diverging evolution.
Oh, yeah, I think we’re doing a panel discussion about science media sometime today. I have heard that it’s at 4:00, but I think that’s wrong: the short outline of events lists a Media Workshop (I think that’s us!) from 7 to 9pm in the Curtis Room at the Hyatt. I’ll start panicking right after the science sessions end this afternoon and run around and find out what’s what, when, and where. They can’t start without me, can they? GrrlScientist wouldn’t abandon me, but I don’t know about that sneaky Lynch fellow.
Almost ten years ago, there was a spectacular fossil discovery in China: microfossils, tiny organisms preserved by phosphatization, that revealed amazing levels of fine detail. These specimens were identified as early animal embryos on the basis of a number of properties.
There are some concerns about the interpretation, though. One troubling aspect of their distribution is that they are all only in the cleavage stage: we don’t see any gastrulas, the stage at which embryonic cells undergo shape changes and begin to move in a specific, directed manner. Studies of taphonomy (analyses of the processes that lead to fossilization) have shown that these later stages are particularly difficult to preserve, which potentially explains why we’re seeing a biased sample. Another unusual bias in the sample is that all of the embryos exhibit that regularity of division that produces equal-sized blastomeres—yet many invertebrate embryos have early asymmetric cleavages that produce recognizable, stereotyped distributions of cells. That asymmetry could be a feature that evolved late, but at the same time, some of the fossils were described as resembling molluscan trefoil embryos. Why aren’t the examples of early asymmetry translated into a later asymmetry?
Now there’s another reason to question the identity of the Doushantuo microfossils: they may be bacterial.
Once upon a time, in Paris in 1830, Etienne Geoffroy St. Hilaire debated Georges Léopole Chrétien Frédéric Dagobert,
Baron Cuvier on the subject of the unity of organismal form. Geoffroy favored the idea of a deep homology, that all animals shared a common archetype: invertebrates with their ventral nerve cord and dorsal hearts were inverted vertebrates, which have a dorsal nerve cord and ventral hearts, and that both were built around or within an idealized vertebra. While a thought-provoking idea, Geoffroy lacked the substantial evidence to make a persuasive case—he had to rely on fairly superficial similarities to argue for something that, to those familiar with the details, appeared contrary to reason and was therefore unconvincing. Evolutionary biology has changed that — the identification of relationships and the theory of common descent has made it unreasonable to argue against origins in a common ancestor — but that difficult problem of homology remains. How does one argue that particular structures in organisms divided by 600 million years of change are, in some way, based on the same ancient organ?
One way is sheer brute force. Characterize every single element of the structures, right down to the molecules of which they are made, and make a quantitative argument that the weight of the evidence makes the conclusion that they are not related highly improbable. I’ll summarize here a recent paper that strongly supports the idea of homology of the vertebrate and arthropod heart and vascular systems.
Today, I gave my final lecture in developmental biology this term. We have one more class session which will be a final discussion, but I’m done yapping at them. Since I can’t possibly teach them everything, I offered some suggestions on what to read next, if they’re really interested in developmental biology. They’ve gotten the fundamentals of the dominant way of looking at development now, that good ol’ molecular genetics centered modern field of evo-devo, but I specifically wanted to suggest a few titles to shake them up a little bit and start thinking differently.
For the student who is interested in the field, but doesn’t feel that development is necessarily their discipline, I recommended Richard Lewontin’s The Triple Helix: Gene, Organism, and Environment(amzn/b&n/abe/pwll). It’s short, it’s easy, and it’s a good counterweight to the usual gene-happy approach we see in developmental biology.
Since we are a liberal arts university, and we value a philosophical approach in addition to the usual bluntly pragmatic tactics we follow in the sciences, I also recommended one work of philosophy: The Ontogeny of Information: Developmental Systems and Evolution(amzn/b&n/abe/pwll), by Susan Oyama. That one is not an easy read, except maybe to the more academically minded. I mentioned that Developmental Systems Theory does not have the powerful research program that is making evo-devo so successful, but it’s still a usefully different way of thinking about the world.
If any of my students wanted to go on to grad school in developmental biology, and hoped to make it a profession, I had to tell them that they are required to read D’Arcy Wentworth Thompson’s On Growth and Form(amzn/b&n/abe/pwll). It’s old, it’s a little bit weird, but it’s still a major touchstone in the discipline.
Lastly, I told them that there was one more book they had to read if they wanted to consider a career in development: Developmental Plasticity and Evolution(amzn/b&n/abe/pwll), by Mary Jane West-Eberhard. If I were a young graduate student in the field right now, I think I could just open that book to a random page and find an interesting and challenging research problem right there. I might have to flip through a few dozen pages before I found one that wasn’t impossibly hard, but hey, it’s one of those books that fills you in on the array of issues that people are worrying over at the edge of the science.
I don’t think any of these would be a good foundation for an undergraduate course (either Thompson or West-Eberhard or Oyama would probably have a lethal effect on the brain of any unprepared student trying to plow through them), but they’d be great mind-stretchers for any student planning to move on.
So all my lecturing is done for the term, and all that’s left are monstrous piles of grading that will grow ominously in the next week and a half even as I struggle to keep up, and then I can try to polish it all off by Cephalopodmas.
One of my favorite signal transduction pathways (what? You didn’t know that true nerds had favorite molecular pathways?) is the one mediated by the receptor Notch. Notch is one of those genes in the metazoan toolkit that keeps popping up in all kinds of different contexts—it’s the adjustable wrench of the toolbox, something that handles a general problem very well and therefore gets reused over and over again, and the list of places where it is expressed in Drosophila is impressive.
I found these on youtube, a couple of nice cartoony animations of the development of the urogenital system. This is one of the weirder modules in organogenesis, I think; many strange things go on that are relics of ancestral states. We actually build three pairs of kidneys—pronephros, mesonephros, and metanephros—and throw each one away in succession, except the last. Both sexes form paramesonephric (or Müllerian) ducts, in blue in the animation, and these form the core of the female plumbing, but again, males basically throw it away and use a more primitive duct (the mesonephric or Wolffian ducts, in green). It’s a bizarre way to construct an organ, but what’s going on is that we have two systems, excretion and reproduction, tied together in ways that constrain the other’s development, and each is building on elements of the other.
It’s in French, but that shouldn’t slow anyone down. It’s easy to figure out what “paramesonephrique” must refer to, for instance.
Males:
Females:
