Jonathan Wells gets everything wrong, again

I was just catching up on a few blogs, and noticed all this stuff I missed about Jonathan Wells’ visit to Oklahoma. And then I read Wells’ version of the event, and just about choked on my sweet mint tea.

The next person–apparently a professor of developmental biology–objected that the film ignored facts showing the unity of life, especially the universality of the genetic code, the remarkable similarity of about 500 housekeeping genes in all living things, the role of HOX genes in building animal body plans, and the similarity of HOX genes in all animal phyla, including sponges. 1Steve began by pointing out that the genetic code is not universal, but the questioner loudly complained that 2he was not answering her questions. I stepped up and pointed out that housekeeping genes are similar in all living things because without them life is not possible. I acknowledged that HOX gene mutations can be quite dramatic (causing a fly to sprout legs from its head in place of antennae, for example), but 3HOX genes become active midway through development, 4long after the body plan is already established. 5They are also remarkably non-specific; for example, if a fly lacks a particular HOX gene and a comparable mouse HOX gene is inserted in its place, the fly develops normal fly parts, not mouse parts. Furthermore, 6the similarity of HOX genes in so many animal phyla is actually a problem for neo-Darwinism: 7If evolutionary changes in body plans are due to changes in genes, and flies have HOX genes similar to those in a horse, why is a fly not a horse? Finally, 8the presence of HOX genes in sponges (which, everyone agrees, appeared in the pre-Cambrian) still leaves unanswered the question of how such complex specified genes evolved in the first place.

The questioner became agitated and shouted out something to the effect that HOX gene duplication explained the increase in information needed for the diversification of animal body plans. 9I replied that duplicating a gene doesn’t increase information content any more than photocopying a paper increases its information content. She obviously wanted to continue the argument, but the moderator took the microphone to someone else.

It blows my mind, man, it blows my freakin’ mind. How can this guy really be this stupid? He has a Ph.D. from UC Berkeley in developmental biology, and he either really doesn’t understand basic ideas in the field, or he’s maliciously misrepresenting them…he’s lying to the audience. He’s describing how he so adroitly fielded questions from the audience, including this one from a professor of developmental biology, who was no doubt agitated by the fact that Wells was feeding the audience steaming balls of rancid horseshit. I can’t blame her. That was an awesomely dishonest/ignorant performance, and Wells is proud of himself. People should be angry at that fraud.

I’ve just pulled out this small, two-paragraph fragment from his longer post, because it’s about all I can bear. I’ve flagged a few things that I’ll explain — the Meyer/Wells tag team really is a pair of smug incompetents.

1The genetic code is universal, and is one of the pieces of evidence for common descent. There are a few variants in the natural world, but they are the exceptions that prove the rule: they are slightly modified versions of the original code that are derived by evolutionary processes. For instance, we can find examples of stop codons in mitochondria that have acquired an amino acid translation. You can read more about natural variation in the genetic code here.

2That’s right, he wasn’t answering her questions. Meyer was apparently bidding for time until the big fat liar next to him could get up a good head of steam.

3This implication that Hox gene expression is irrelevant because it is “late” was a staple of Wells’ book, Icons of Evolution and the Politically Incorrect Guide to Darwinism and Intelligent Design. It’s a sham. The phylotypic stage, when the Hox genes are exhibiting their standard patterns of expression, of humans is at 4-5 weeks (out of 40 weeks), and in zebrafish it’s at 18-24 hours. These are relatively early events. The major landmarks before this period are gastrulation, when major tissue layers are established, and neurulation, when the neural tube forms. Embryos are like elongate slugs with the beginnings of a few tissues before this time.

4What? Patterned Hox gene expression is associated with the establishment of the body plan. Prior to this time, all the embryonic chordate has of a body plan is a couple of specified axes, a notochord, and a dorsal nerve tube. The pharyngula stage/phylotypic stage is the time when Hox gene expression is ordered and active, when organogenesis is ongoing, and when the hallmarks of chordate embryology, like segmental myotomes, a tailbud, and branchial arches are forming.

5Hox genes are not non-specific. They have very specific patterning roles; you can’t substitute abdominal-B for labial, for instance. They can be artificially swapped between individuals of different phyla and still function, which ought, to a rational person, be regarded as evidence of common origin, but they definitely do instigate the assembly of different structures in different species, which is not at all surprising. When you put a mouse gene in a fly, you are transplanting one gene out of the many hundreds of developmental genes needed to build an eye; the eye that is assembled is built of 99% fly genes and 1% (and a very early, general 1%) mouse genes. If it did build a mouse eye in a fly, we’d have to throw out a lot of our understanding of molecular genetics and become Intelligent Design creationists.

Hox genes are initiators or selectors; they are not the embryonic structure itself. Think of it this way: the Hox genes just mark a region of the embryo and tell other genes to get to work. It’s as if you are contracting out the building of a house, and you stand before your subcontractors and tell them to build a wall at some particular place. If you’ve got a team of carpenters, they’ll build one kind of wall; masons will build a different kind.

6No, the similarity of Hox genes is not a problem. It’s an indicator of common descent. It’s evidence for evolution.

7Good god.

Why is a fly not a horse? Because Hox genes are not the blueprint, they are not the totality of developmental events that lead to the development of an organism. You might as well complain that the people building a tarpaper shack down by the railroad tracks are using hammers and nails, while the people building a MacMansion on the lakefront are also using hammers and nails, so shouldn’t their buildings come out the same? Somebody who said that would be universally regarded as a clueless moron. Ditto for a supposed developmental biologist who thinks horses and flies should come out the same because they both have Hox genes.

8You can find homeobox-containing genes in plants. All that sequence is is a common motif that has the property of binding DNA at particular nucleotide sequences. What makes for a Hox gene, specifically, is its organization into a regulated cluster. How such genes and gene clusters could arise is simply trivial in principle, although working out the specific historical details of how it happened is more complex and interesting.

The case of sponges is enlightening, because they show us an early step in the formation of the Hox cluster. Current thinking is that sponges don’t actually have a Hox cluster (the first true Hox genes evolved in cnidarians), they have a Hox-like cluster of what are called NK genes. Apparently, grouping a set of transcription factors into a complex isn’t that uncommon in evolution.

9If you photocopy a paper, the paper doesn’t acquire more information. But if you’ve got two identical twins, A who is holding one copy of the paper, and B who is holding two copies of the same paper, B has somewhat more information. Wells’ analogy is a patent red herring.

The ancestral cnidarian proto-Hox cluster is thought to have contained four Hox genes. Humans have 39 Hox genes organized into four clusters. Which taxon contains more information in its Hox clusters? This is a trick question for Wells; people with normal intelligence, like most of you readers, would have no problem recognizing that 39 is a bigger number than 4. Jonathan Wells seems to have missed that day in his first grade arithmetic class.

It’s appalling, but this is the Discovery Institute’s style: to trot out a couple of crackpots with nice degrees, who then proceed to make crap up while pretending to be all sincere and informed and authoritative. It’s an annoying trick, and I can understand entirely why a few intelligent people with actual knowledge in the audience might find the performance infuriating. I do, too.

Darwinopterus and mosaic, modular evolution

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It’s yet another transitional fossil! Are you tired of them yet?

Darwinopterus modularis is a very pretty fossil of a Jurassic pterosaur, which also reveals some interesting modes of evolution; modes that I daresay are indicative of significant processes in development, although this work is not a developmental study (I wish…having some pterosaur embryos would be exciting). Here it is, one gorgeous animal.

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Figure 2. Holotype ZMNH M8782 (a,b,e) and referred specimen YH-2000 ( f ) of D. modularis gen. et sp. nov.: (a) cranium and mandibles in the right lateral view, cervicals 1-4 in the dorsal view, scale bar 5cm; (b) details of the dentition in the anterior tip of the rostrum, scale bar 2cm; (c) restoration of the skull, scale bar 5cm; (d) restoration of the right pes in the anterior view, scale bar 2 cm; (e) details of the seventh to ninth caudal vertebrae and bony rods that enclose them, scale bar 0.5 cm; ( f ) complete skeleton seen in the ventral aspect, except for skull which is in the right lateral view, scale bar 5 cm. Abbreviations: a, articular; cr, cranial crest; d, dentary; f, frontal; j, jugal; l, lacrimal; ldt, lateral distal tarsal; m, maxilla; mdt, medial distal tarsal; met, metatarsal; n, nasal; naof, nasoantorbital fenestra; p, parietal; pd, pedal digit; pf, prefrontal; pm, premaxilla; po, postorbital; q, quadrate; qj, quadratojugal; sq, squamosal; ti, tibia.

One important general fact you need to understand to grasp the significance of this specimen: Mesozoic flying reptiles are not all alike! There are two broad groups that can be distinguished by some consistent morphological characters.

The pterosaurs are the older of the two groups, appearing in the late Triassic. They tend to have relatively short skulls with several distinct openings, long cervical (neck) ribs, a short metacarpus (like the palm or sole of the foot), a long tail (with some exceptions), and an expanded flight membrane suspended between the hind limbs, called the cruropatagium. They tend to be small to medium-sized.

The pterodactyls are a more derived group that appear in the late Jurassic. Their skulls are long and low, and have a single large opening in front of the eyes, instead of two. Those neck ribs are gone or reduced, they have a long metacarpus and short tails, and they’ve greatly reduced the cruropatagium. Some of the pterodactyls grew to a huge size.

Here’s a snapshot of their distribution in time and phylogenetic relationships. The pterosaurs are in red, and the pterodactyls are in blue.

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Time-calibrated phylogeny showing the temporal range of the main pterosaur clades; basal clades in red, pterodactyloids in blue; known ranges of clades indicated by solid bar, inferred ‘ghost’ range by coloured line; footprint symbols indicate approximate age of principal pterosaur track sites based on Lockley et al. (2008); stratigraphic units and age in millions of years based on Gradstein et al. (2005). 1, Preondactylus; 2, Dimorphodontidae; 3, Anurognathidae; 4, Campylognathoididae; 5, Scaphognathinae; 6, Rham- phorhynchinae; 7, Darwinopterus; 8, Boreopterus; 9, Istiodactylidae; 10, Ornithocheiridae; 11, Pteranodon; 12, Nyctosauridae; 13, Pterodactylus; 14, Cycnorhamphus; 15, Ctenochasmatinae; 16, Gnathosaurinae; 17, Germanodactylus; 18, Dsungaripteridae; 19, Lonchodectes; 20, Tapejaridae; 21, Chaoyangopteridae; 22, Thalassodromidae; 23, Azhdarchidae. Abbreviations: M, Mono- fenestrata; P, Pterodactyloidea; T, Pterosauria; ca, caudal vertebral series; cv, cervical vertebral series; mc, metacarpus; na, nasoantorbital fenestra; r, rib; sk, skull; v, fifth pedal digit.

Darwinopterus is in there, too—it’s the small purple box numbered “7”. You can see from this diagram that it is a pterosaur in a very interesting position, just off the branch that gave rise to the pterodactyls. How it got there is interesting, too: it’s basically a pterosaur body with the head of a pterodactyl. Literally. The authors of this work carried out multiple phylogenetic analyses, and if they left the head out of the data, the computer would spit out the conclusion that this was a pterosaur; if they left the body out and just analyzed the skull, the computer would declare it a pterodactyl.

What does this tell us about evolution in general? That it can be modular. The transitional form between two species isn’t necessarily a simple intermediate between the two in all characters, but may be a mosaic: the anatomy may be a mix of pieces that resemble one species more than the other. In this case, what happened in the evolution of the pterodactyls was that first a pterodactyl-like skull evolved in a pterosaur lineage, and that was successful; later, the proto-pterodactyls added the post-cranial specializations. Not everything happened all at once, but stepwise.

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Schematic restorations of a basal pterosaur (above), Darwinopterus (middle) and a pterodactyloid (below) standardized to the length of the DSV, the arrow indicates direction of evolutionary transformations; modules: skull (red), neck (yellow), body and limbs (monochrome), tail (blue); I, transition phase one; II, transition phase two.

This should be a familiar concept. In pterodactyls, skulls evolved a specialized morphology first, and the body was shaped by evolutionary processes later. We can see a similar principle in operation in the hominid lineage, too, but switched around. We evolved bipedalism first, in species like Ardipithecus and Australopithecus, and the specializations of our skull (to contain that big brain of which we are so proud) came along later.

As I mentioned at the beginning, this is an example of development and evolution in congruence. We do find modularity in developmental process — we have genetic circuits that are expressed in tissue- and region-specific ways in development. We can talk about patterns of gene expression that follow independent programs to build regions of the body, under the control of regional patterning genes like the Hox complex. In that sense, what we see in Darwinopterus is completely unsurprising.

What is interesting, though, is that these modules, which we’re used to seeing within the finer-grained process of development, also retain enough coherence and autonomy to be visible at the level of macroevolutionary change. It caters to my biases that we shouldn’t just pretend that all the details of development are plastic enough to be averaged out, or that the underlying ontogenetic processes will be overwhelmed by the exigencies of environmental factors, like selection. Development matters — it shapes the direction evolution can take.

Lü J, Unwin DM, Jin X, Liu Y, Ji Q (2009) Evidence for modular evolution in a long-tailed pterosaur with a pterodactyloid skull. Proc. R. Soc. B published online 14 October 2009 doi: 10.1098/rspb.2009.1603

I should have mentioned that Darren Naish has a very thorough write-up on Darwinopterus!

Isn’t pleiotropy handy?

Look at the interesting snake found in China — it’s got a leg.

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How can this happen? Genes are pleiotropic — they tend to have lots of different functions. The genes involved in making a limb are also expressed in other places; for instance, the Hox genes that specify identity along the length of the body are also reused in specifying identity along the length of the limb. What that means is that when the snake evolved limblessness, it didn’t do so by simply throwing away a collection of leg genes — it couldn’t, not without also destroying genes that functioned in generating its body plan. Instead, it evolved genes or modified the regulation of genes to actively suppress limb development…but the genes to build a limb are still in the genome, and still functional, and still actively working in other ways.

What most likely happened here is that some environmental agent suppressed the suppressor, allowing the old developmental program for a limb to be re-expressed. The retention of such programs is, of course, evidence that this animal evolved from limbed ancestors.

It would be interesting to know what triggered this change. It’s not likely to be genetic (the asymmetry suggests that), but is probably a consequence of some pollutants that disrupt development. It’s not a good sign, anyway.

Some good suggestions from the comments: it may not even be a teratogenic deformity. It could just be a poor lizard that punched a claw through the abdominal wall as it was being digested, and the snake was briefly trundling about in pain from the injury.

We need to do a dissection!

Gene regulatory networks and conserved noncoding elements

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We miss something important when we just look at the genome as a string of nucleotides with scattered bits that will get translated into proteins — we miss the fact that the genome is a dynamically modified and expressed sequence, with patterns of activity in the living cell that are not readily discerned in a simple series of As, Ts, Gs, and Cs. What we can’t see very well are gene regulatory networks (GRNs), the interlinked sets of genes that are regulated in a coordinated fashion in cells and tissues.

[Read more…]

The evolution of Hedgehog

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PLoS has recently published a highly speculative but very interesting paper on how a particular signaling pathway, the Hedgehog pathway, might have evolved. It’s at a fairly early stage in hypothesis testing, which is one of the things that makes it interesting — usually all you see published is the product of a great deal of data collection and experiment and testing, which means the scientific literature gives a somewhat skewed view of the process of science, letting the outsider mainly see work that has been hammered and polished, while hiding the rougher drafts that would better allow us to see how the story started and was built. It’s informative in particular for those who follow the creationist “literature”, which often crudely apes the products of actual working science, but lacks the sound methodological underpinnings. In particular, creationism completely misses the process of poking at the real world to develop ideas, since they begin with their conclusion.

So take this description as a work in progress — we’re seeing the dynamic of building up a good working model. As usual, it starts on a sound foundation of confirmed, known evidence, makes a reasonably hypothesis on the basis of the facts, and then proposes a series of research avenues with predicted results that would confirm the idea.

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Brian Goodwin, 1931-2009

It’s sad to see that we’ve lost Brian Goodwin, one of the genuinely original (but not always right!) thinkers of our time. There aren’t many left of the old structuralist tradition in biology, the kind of non-genetic purists who tried to analyze development in terms of the fundamental physical and chemical properties of the organism—they’ve been swallowed up and lost in a triumphal molecular biology research program.

Edge has a nice interview with and essay by Goodwin — they’re good places to start. If that whets your appetite, you should also read his book, How the Leopard Changed Its Spots : The Evolution of Complexity(amzn/b&n/abe/pwll), which is aimed at general audiences and is a good overview of why we should look at more than just genes to explain form.

He was an advocate for one view of nature, and I think he missed the mark by neglecting genes as much as he did; we know now that a lot of details of morphology are directly affected in subtle and not-so-subtle ways by the genetics of the organism. But I think we can also make a case that the modern molecular biological approach is also missing a significant element. Every biologist ought to read a little Goodwin, just to leaven their picture of how biology works with his special perspective.

What caused the Cambrian explosion? MicroRNA!

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No, not really — my title is a bit of a sensationalistic exploitation of the thesis of a paper by Peterson, Dietrich, and McPeek, but I can buy into their idea that microRNAs (miRNAs) may have contributed to the pattern of metazoan phylogenies we see now. It’s actually a thought-provoking concept, especially to someone who favors the evo-devo view of animal evolution. And actually, the question it answers is why we haven’t had thousands of Cambrian explosions.

In case you haven’t been keeping up, miRNAs are a hot topic in molecular genetics: they are short (21-23 nucleotides) pieces of single stranded RNA that are not translated into protein, but have their effect by binding to other strands of messenger RNA (mRNA) to which they complement, effectively down-regulating expression of that messenger. They play an important role in regulating the levels of expression of other genes.

One role for miRNAs seems to be to act as a kind of biological buffer, working to limit the range of effective message that can be operating in the cell at any one time. Some experiments that have knocked out specific miRNAs have had a very interesting effect: the range of expressed phenotypes for the targeted message gene increases. The presence or absence of miRNA doesn’t actually generate a novel phenotype, it simply fine-tunes what other genes do — and without miRNA, some genes become sloppy in their expression.

This talk of buffering expression immediately swivels a developmental biologist’s mind to another term: canalization. Canalization is a process that leads organisms to produce similar phenotypes despite variations in genotype or the environment (within limits, of course). Development is a fairly robust process that overcomes genetic variations and external events to yield a moderately consistent outcome — I can raise fish embryos at 20°C or at 30°C, and despite differences in the overall rate of growth, the resultant adult fish are indistinguishable. This is also true of populations in evolution: stasis is the norm, morphologies don’t swing too widely generation after generation, but still, we can get some rapid (geologically speaking) shifts, as if forms are switching between a couple of stable nodes of attraction.

Where the Cambrian comes into this is that it is the greatest example of a flowering of new forms, which then all began diverging down different evolutionary tracks. The curious thing isn’t their appearance — there is evidence of a diversity of forms before the Cambrian, bacteria had been flourishing for a few billion years, etc., and what happened 500 million years ago is that the forms became visible in the fossil record with the evolution of hard body parts — but that these phyla established body plans that they were then locked into, to varying degrees, right up to the modern day. What the authors are proposing is that miRNAs might be part of the explanation for why these lineages were subsequently channeled into discrete morphological pathways, each distinct from the other as chordates and arthropods and echinoderms and molluscs.

[Read more…]

Martin Chalfie: GFP and After

Chalfie is interested in sensory mechanotransduction—how are mechanical deformations of cells converted into chemical and electrical signals. Examples are touch, hearing, balance, and proprioception, and (hooray!) he references development: sidedness in mammals is defined by mechanical forces in early development. He studies this problem in C. elegans, in which 6 of 302 nerve cells detect touch. It’s easy to screen for mutants in touch pathways just by tickling animals and seeing if they move away. They’ve identified various genes, in particular a protein that’s involved in transducing touch into a cellular signal.

They’ve localized where this gene is expressed. Most of these techniques involved killing, fixing, and staining the animals. He was inspired by work of Shimomura, as described by Paul Brehm that showed that Aequorin + Ca++ + GFP produces light, and got in touch with Douglas Prasher, who was cloning GFP, and got to work making a probe that would allow him to visualize the expression of interesting genes. It was a gamble — no one knew if there were additional proteins required to turn the sequence into a glowing final product…but they discovered that they could get functional product in bacteria within a month.

They published a paper describing GFP as a new marker for gene expression, which Science disliked because of the simple title, and so they had to give it a cumbersome title for the reviewers, which got changed back for publication. They had a beautiful cover photo of a glowing neuron in the living animal.

Advantages of GFP: heritable, relatively non-invasive, small and monomeric, and visible in living tissues. Roger Tsien worked to improve the protein and produce variants that fluroesced at different wavelengths. There are currently at least 30,000 papers published that use fluroescent proteins, in all kinds of organisms, from bunnies to tobacco plants.

He showed some spectacular movies from Silverman-Gavrila of dividing cells with tubulin/GFP, and another of GFP/nuclear localization signal in which nuclei glowed as they condensed after division, and then disappeared during mitosis. Sanes and Lichtman’s brainbow work was shown. Also cute: he showed the opening sequence of the Hulk movie, which is illustrated with jellyfish fluorescence (he does not think the Hulk is a legitimate example of a human transgenic.)

Finally, he returned to his mechanoreceptor work and showed the transducing cells in the worm. One of the possibilities this opened up was visual screening for new mutants: either looking for missing or morphologically aberrant cells, or even more subtle things, like tagging expression of synaptic proteins so you can visually scan for changes in synaptic function or organization.

He had a number of questions he could address: how are mechanotransducers generated, how is touch transduced, what is the role of membrane lipids, can they identify other genes important in touch, and what turns off these genes?

They traced the genes involved in turning on the mec-3 gene; the pathway, it turned out, was also expressed in other cells, but they thought they identified other genes involved in selectively regulating touch sensitivity. One curious thing: the mec genes are transcribed in other cells that aren’t sensitive, but somehow are not translated.

They are searching for other touch genes. The touch screen misses some relevant genes because they have redundant alternatives, or are pleiotropic so other phenotypes (like lethality) obscure the effect. One technique is RNAi, and they made an interesting observation. Trying about 17000 RNAis, they discovered that 600 had interesting and specific effects, 1100 were lethal, and about 15,000 had no effect at all. The majority of genes are complete mysteries to us. They’ve developed some techniques to get selective incorporation of RNAis into just neurons of C. elegans, so they’re hoping to uncover more specific neural effects. One focus is on the integrin signaling pathway in the nervous system, which they’ve knocked out and found that it demolishes touch sensitivity — a new target!

They are now using a short-lived form of GFP that shuts down quickly, so they’ve got a sharper picture of temporal patterns of gene activity.

Chalfie’s summary:

  • Scientific progress is cumulative.

  • Students and post-docs are the lab innovators.

  • Basic research is essential. Who would have thought working on jellyfish would lead to such powerful tools?

  • All life should be studied; not just model organisms.

Chalfie is an excellent speaker and combined a lot of data with an engaging presentation.

Digit numbering and limb development

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Answers in Genesis has evolutionary biology on the run now. In an article from 2002, Ostrich eggs break dino-to-bird theory, they explain that development shows that evolution is all wrong, since developmental pathways in different animals are completely different, and can’t possibly be the result of gradual transformations.

The first piece of evidence against evolution is the old avian digit problem. Birds couldn’t have evolved from dinosaurs, because they have the wrong finger order!

The research conclusively showed that only digits two, three and four (corresponding to our index, middle and ring fingers) develop in birds. This contrasts with dinosaur hands that developed from digits one, two and three. Feduccia pointed out:

‘This creates a new problem for those who insist that dinosaurs were ancestors of modern birds. How can a bird hand, for example, with digits two, three and four evolve from a dinosaur hand that has only digits one, two and three? That would be almost impossible.’

The second problem is that frogs and people develop hands in completely different ways, ways that are even more different than the order of the digits.

This is not the only example where superficially homologous structures actually develop in totally different ways. One of the most commonly argued proofs of evolution is the pentadactyl limb pattern, i.e. the five-digit limbs found in amphibians, reptiles, birds and mammals. However, they develop in a completely different manner in amphibians and the other groups. To illustrate, the human embryo develops a thickening on the limb tip called the AER (apical ectodermal ridge), then programmed cell death (apoptosis) divides the AER into five regions that then develop into digits (fingers and toes). By contrast, in frogs, the digits grow outwards from buds as cells divide (see diagram, right).

Dang. I might as well hang it up right now. There is no possible way around these intractable differences. Take me, Jesus, I have seen the ligh…oh, wait a minute. That isn’t right. It looks to me like Jonathan Sarfati is just hopelessly confused on the first problem (I can’t really blame him, though—it is a complicated issue that has been the subject of scientific arguments for two centuries), and is simply completely wrong on the second (and that one I do blame him for. Tsk, tsk.)

So first, let’s tackle the tricky problem, digit identity in evolution. Extend your right hand out in front of you, palm down. Your thumb should be sticking out towards the left, and by convention, that’s Digit I. Counting from left to right, your index finger is Digit II, middle finger is Digit III, ring finger is digit IV, and your pinky is Digit V. We have the primitive pentadactyl (five-fingered) hand, so figuring out who is who is fairly easy. The difficulties arise in species that have reduced the number of their digits—when they extend their three-fingered hand, we have to figure out which digits are missing before we assign numbers to the remaining fingers.

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One way is by looking at the adult anatomy. Looking at your hand, you probably notice that your thumb is quantitatively different from the other fingers: it only has two joints, instead of three. This is common, that Digit I has fewer phalanges, or segments, than the others, and this is the kind of property that allows anatomists to figure out whether Digit I is present or not. To the right, for instance, is the hand of the raptor Deinonychus (the left hand, sorry to confuse you) with its digit numbering, from DI to DII to DIII, an assignment that was made on the basis of the anatomy. You can see that the ‘thumb’, DI, has fewer phalanges than the others.

You can try to do the same thing with the digits of birds, but it’s harder. Avian digits are reduced and fused into that pointy thing you find at the end of a chicken wing, and it takes an expert to sort out what bones are blended together in there. Anatomists tried, though, and initially and long ago (Meckel came to this conclusion in 1825), decided the bones were numbered DI, DII, and DIII, just like the ones we see in three-fingered dinosaurs…so no dilemma, right?

Wrong. There’s another way of looking at the identity of these bones, and that is by watching them develop. What some birds do is start to make five fingers—they form four or five little nubbins of cartilage, called condensations, and then shut down the development of some of them. What another old time anatomist noticed (Owen, in 1836) was that one of the condensations that got thrown away was the first one—which means that the bird digits are actually derived from Condensation II, Condensation III, and Condensation IV. The data is even stronger in this day of molecular markers: bird digits arise embryonically from the second, third, and fourth cartilaginous condensations.

Now this is a complication for evolution. We have three-fingered dinosaurs, and three-fingered birds, but it looks like they aren’t the same fingers. Bird ancestors would have had to resurrect their discarded Digit IV, then eliminate Digit I, all before fusing the whole assemblage into a bony gemisch anyway. It’s not parsimonious at all. (Of course, it’s even less parsimonious to throw away more than a century of data supporting evolution, as Jonathan Sarfati would like us to do.)

There is another, better explanation that Wagner and Gauthier have made that clarifies everything to me, at least.

Note that anatomists initially assigned digit numbers I, II, and III to bird limbs on the basis of their form, but later had to revise that to II, III, and IV on the basis of embryology. Dinosaur digits are assigned numbers I, II, and III on the basis of their adult form (which is admittedly much less ambiguous than adult bird digits!)…but what about their embryology? If we had access to information about expression of molecular markers and early condensations in the dinosaur limb, would we have to revise their digit numbers?

We don’t have fetal dinosaur hands to experiment on, but our growing knowledge about how limbs develop suggests that that might just be the case. This diagram illustrates the sequence of development in the hand of an alligator (a) and an ostrich (b).

i-3d4cb812c44b43be89d64bf407329866-metapterygial_axis.gif
(Click for larger image)

What you’re seeing is the pattern of early condensations in the limb. We tetrapods have a standard pattern: the very first digit to develop as an extension of the limb is Condensation IV, your ring finger, forming what is called the metapterygial axis. Next, the pinky (CV) forms as a little afterthought along one side of the metapterygial axis, and a new axis of condensation hooks over the palm, with the middle finger (CIII) forming next, then the index finger (CII), and lastly the thumb (CI). From a developmental standpoint, the easiest digits to lose are that odd little CV, and the thumb, CI. CI is the very last to form, so you can stop its formation by changing the timing of development in a process called heterochrony, and just halting the development of that axis hooking across the palm early. You can see that in the ostrich, which just stops making fingers after CII, so CI doesn’t form. The hardest digit to lose is CIV, because it’s kind of the lynchpin of the process—all the other digits follow after IV, so it would be difficult to suppress IV without losing all of the other digits. (Who would have thought that the ring finger was so central and important to hand development?)

The numbering of the dinosaur limb is a problem then…it suggests that they don’t have a Digit IV, which looks like a complicated and unlikely thing to do. But they do have a ‘thumb’, or Digit I. How do we resolve this seeming contradiction?

The answer is that there are two developmental processes going on. The first is the formation of the condensations, CI through CV. This process partitions the terminal region into an appropriate number of chunks, but doesn’t actually specify the identity of the digits. The second process takes each of those chunks and assigns a digit identity to them, and this process is to some degree independent of the first and uses a different set of signals. Wolpert et al. have noticed this in modern embryos:

For example, digit identity is specified at a surprisingly late stage in limb development, and identity remains labile even when the digit primordia have formed. It now appears that digit identity is specified by the interdigital mesenchyme and requires BMP signaling. There is also evidence that mechanisms other than a diffusible morphogen operate to lay down the initial pattern of cartilage, which is then modified by a signal from the polarizing region…

What Wagner and Gauthier propose is that three-fingered dinosaurs accomplished that reduction by shedding the two easiest digits to lose, CI and CV, so that if we enumerated them by the same criteria we use in modern birds, they possess Condensations II, III, and IV. What also happened, though, was that there was a frame shift in the mechanism that assigns digit identity, so CII develops as DI, CIII as DII, and CIV as DIII.

i-985af1b7eaa00ab3b9bd5685a64241c6-digit_frameshift.gif

The timing of this shift can be mapped onto saurian phylogeny, and it all makes sense and is consistent. And it doesn’t involve taking seriously the silly sequence of the biblical account, which has birds appearing before all of the land animals.

i-738081af842c6fd8bec2fc1b6b2e98f2-digit_phylogeny.gif
(Click for larger image)

What about Sarfati’s second line of evidence against evolution, that frogs and humans use completely different mechanisms to build their limbs?

Simple answer: it’s all bullshit. It’s a blatant denial of basic information you’ll find in any developmental biology textbook.

We’ve got a pretty good handle on the outline of limb development in multiple tetrapod lineages now, and they all use the same tools. Contrary to Sarfati’s implication, they all have apical ectodermal ridges (with some rare exceptions in a few highly derived, direct-developing frogs) and zones of polarizing activity, they all use the same set of molecules, including FGF-4 and FGF-8 and the same Hox genes and retinoic acid and BMPs. If there’s one thing we know, it’s that limb development is dazzlingly well conserved.

It is true that frogs have less apoptosis between their digits than we do, but that’s because they have webbed feet. Suppress apoptosis in other vertebrates, and you get the same phenomenon, retention of membranous webs between the digits. There is a simple functional reason why they differ in this regard, and it takes advantage of a common property of limb development in all tetrapods.

I can sympathize with Sarfati having difficulty sorting out digit numbering—it’s subtle and sneaky and has puzzled smarter people than either of us. But the uninformed rejection of some of the most straightforward, clearest examples of common mechanisms in development, something that you can find described in the most introductory biology textbook…that’s hard to forgive.

Wagner GP, Gauthier JA (1999) 1,2,3=2,3,4: A solution to the problem of the homology of the digits in the avian hand. Proc. Natl. Acad. Sci. 96:5111-5116.

Wolpert L, Beddington R, Jessel T, Lawrence P, Meyerowitz E, Smith J (2002) Principles of Development. Oxford University Press.

How to build a dinosaur

I’ve been reading a new book by Jack Horner and James Gorman, How to Build a Dinosaur: Extinction Doesn’t Have to Be Forever(amzn/b&n/abe/pwll), and I was pleasantly surprised. It’s a book that gives a taste of the joys of geology and paleontology, talks at some length about a recent scientific controversy, acknowledges the importance of evo-devo, and will easily tap into the vast mad scientist market.

It is a little scattered, in that it seems to be the loosely assembled concatenation of a couple of books, but that’s part of the appeal; read the chapters like you would a collection of short stories, and you’ll get into the groove.

The first part is about Horner’s life in Montana, the Hell Creek formation, and dinosaur collecting. Hand this to any kid and get him hooked on paleontology for life; I recall reading every book I could get my hands on that talked about Roy Chapman Andrews as a young’un, and it permanently twisted me…in a good way. This will have the same effect, and many people will think about heading out to Garfield County for a little dusty adventure. I know I am — all that stands in my way is South Dakota.

A good chunk of the book is about molecules and how they show the relatedness of dinosaurs to birds, and to the work of Horner’s former student, Mary Schweitzer, who discovered soft tissue in T. rex bones. Horner presents a good overview of the subject, but is also appropriately cautious. You’ll get a good feel for the difficulty of finding this material, and for interpreting it; he clearly believes that these are scraps of real T. rex tissue, but how intact it is, what kinds of changes have occurred in it, and how much information will be extractable from these rare bits of preserved collagen (or whatever) is left an open question.

Finally, the subject of the title…Horner was an advisor to the Jurassic Park movies, and right away he dismisses the idea of extracting 65 million year old DNA in enough quantity to reconstitute a dinosaur as clearly nothing but a fantasy. That’s simply not how it can be done. But he does have a grand, long-term plan for recreating a dinosaur.

What is it? Why, it’s developmental biology, of course. Development is the answer to everything.

Here’s his vision, and I found it believable and captivating: start with a modern dinosaur, a chicken, figure out the developmental pathways that make it different from an ancient dinosaur, and tweak them back to the ancestral condition. For instance, birds have lost the long bony tail of their ancestors, reducing it to a little stump called a pygostyle. In the embryo, they start to make a long tail, but then developmental switches put a kink in it and reduce it to a stub. If we could only figure out what specific molecules are signaling the tissue to take this modern reducing path and switch them off, then maybe we could produce a generation of chickens with the long noble tails of a velociraptor.

My first thought was skepticism — it can’t be that easy. There may be a simple network of genes that regulate this one early decision to form a pygostyle from a tail, but there have been tens of millions of years of adaptation by other genes to the modern condition; we’re dealing with a large network of interlinked genes here, and unraveling one step in development doesn’t mean that subsequent steps are still competent to respond in the ancient pattern. But then, thinking about it a little more, one of the properties of the genome is its plasticity and ability to respond in a coherent, integrated way to changes in one part of a gene network. That capacity might mean you could reconstitute a tail.

And then, once you’ve got a tailed chicken, you could work on adding teeth to the jaws. And foreclaws. And while you’re at it, find the little genomic slider that controls body size, and turn it up to 11. What he’s proposing is a step-by-step analysis of chicken-vs.-dinosaur decisions in the developmental pathways, and inserting intentional atavisms into them. This is all incredibly ambitious, and it might not work…but the only way to find out is try. I like that in a scientist. Turning a chicken into a T. rex is a true Mad Scientist project, and one that I must applaud.

One reservation I have about this section of the book is that too much time is spent dwelling over ethical concerns. Need I mention that real Mad Scientists do not fret over the footling trivia of the Institutional Review Board? These are chicken embryos, animals that your average member of the taxpaying public finds so inconsequential that they will pay to have them homogenized into spongy-textured slabs of yellow protein to be slapped onto their McMuffin. Please, people, get some perspective.

As for respecting the chickens themselves, what can be grander and more respectful than this project? I would whisper to my chickens, “With these experiments, I will take your children’s children’s children, and give them great ripping claws like scythes, and razor-sharp serrate fangs like daggers, and I will turn them into multi-story towers of muscle and bone that will be able to trample KFC restaurants as if they were matchboxes.” And their eyes would light up with a feral gleam of primeval ambition, and they would offer me their ovaries willingly. I’d be doing the chickens a favor. Maybe some chicken farmers would have cause to be fearful, but I wouldn’t be working on their embryos, so let them tremble.

Oh, all right. Horner is taking the responsible path and putting some serious thought into the ethics of this kind of experiment, which is the right thing to do. It’s also the kind of project that will generate serious and useful information about developmental networks, even if it fails in its ultimate aim.

But I have a dream, too. Of a day when biotechnology is ubiquitous, and middle-class kids everywhere will have a cheap DNA sequencer and synthesizer in their garages, and a freezer with handy vectors and enzymes for directed insertional mutagenesis. And one day, Mom will come home with a box of fresh guaranteed organic free range chicken eggs, and Junior’s eyes will glitter with a germ of a cunning plan, fed by a little book he found in the library…and 30-foot-tall fanged chickens will triumphantly stride the cul-de-sacs of suburbia, and the roar of the dinosaur will be heard once again.