Evo-devo on NOVA

Don’t miss it! Tonight at 8pmET/7pm Central, NOVA is showing What Darwin Never Knew, a documentary about evo-devo. I shall be glued to my TV tonight!

I just started watching it. So far, it’s a nice little history of Darwin and his ideas; Sean Carroll is a good person to have talking up the story. It’s nothing new yet, and nothing about evo-devo so far — I’m waiting impatiently for it.

Twenty minutes in, we get a little embryology: limb rudiments in snake embryos, tooth rudiments in whale embryos, and branchial arches in human embryos. These are shown as uncompromising evidence of limbed, toothed, and gilled ancestors — cue wails of horror from the Discovery Institute…now.

They also discuss variation in dog breeds. More development, please!

Hmmm. We’re past the half-hour mark, and it’s all selection, selection, selection. It’s clearly explained and it’s a useful intro to the general concept of Darwinian evolution…but I was hoping for something a little more focused and novel. This documentary is supposed to be based on Carroll’s Endless Forms Most Beautiful and The Making of the Fittest, but we’re getting bogged down in very general material and not yet getting to the meat of either book.

Now we’re getting an explanation of DNA sequences as a code (alarms are whooping at the Discovery Institute again), with pigment changes in different varieties of mice as an example. We’re also getting brief mentions of genetic changes that produce color vision and cold-adaptedness in icefish (those are straight from Making of the Fittest).

This bugs me. They’re talking about the number of genes in the human genome as a big surprise — we “only” have 23,000 genes. I don’t know; it always seems to be dropped out of context. How many genes should we have expected?

Some nice animations of transformations of embryos are shown, illustrating (as Haeckel did) that all vertebrates began with a common body plan that diverges in detail over the course of development — I hope an ambulance is on standby in Seattle near the DI.

Unfortunately, they’re using developmental changes as an explanation for why we have too few genes to satisfy our egos. Again, this bugs me: fruit flies and people have comparable numbers of genes, and also comparable developmental processes.

Anyway, it does lead into some useful discussion of evolving pigmentation spots in Drosophila, which leads further into regulatory DNA. Unfortunately, this bit has some confusing stuff. The documentary conflates regulatory DNA with junk DNA — regulatory is not and has not been regarded as junk! — and might lead some viewers into thinking that all junk DNA has developmental functions. It does not.

They do have some nice illustrations of experiments used to tag regulatory sequences with marker genes, making flies with glowing spots on their wings.

Another good example: they’re showing the evolution of regulatory switches in stickleback fish. Cool, it’s David Kingsley! They’re showing how the differences between marine (spiky) and freshwater (non-spiky) is not in the coding sequences of a few genes, but in the regulatory regions of those genes.

Hmm. Repetitive flashy graphics of DNA are beginning to hurt my eyes.

We also get a summary of Tabin’s work on the genes behind different beak morphologies in finches. The same genes are involved, but the differences are in the timing and strength of activation of these genes. The genes involved are also explained as regulatory genes — the genes that switch other genes off and on. This is starting to get into stuff I’d find useful in the classroom.

Hey, now it’s Neil Shubin’s turn to talk about the evolution of limbs. This show is turning out to be a nice introduction to the superstars of evo-devo!

More cool stuff: video from Ellesmere Island, and the discovery of Tiktaalik. Also an amusing animation of the fossil coming to life in Shubin’s lab, which I’m pretty sure doesn’t actually happen.

The show quickly moves from fossils to molecules, and describes efforts to isolate the limb regulatory pathway from modern relatives (paddlefish) of the ancient tetrapods. We get to hear a little bit about Hox genes. Oooh, I could use some of those sequences illustrating the pattern of Hox gene expression in the limb…

We don’t need new genes to make new structures: changing the timing and strength of expression of genes within an existing pathway can create new features.

At least, a clear statement of what Darwin didn’t know that the documentary is describing: we are deriving mechanistic explanations for the processes that produce morphological diversity. It’s a consequence of subtle shifts in the timing and intensity of gene expression in a hierarchy of well-established functional pathways.

We’re getting into the last half-hour here, and the emphasis is switching to humans. Ho-hum. Humans are really crummy experimental models, so I guess we’re not going to get deeper into those mechanisms, but will tap into the audience’s self-centeredness, which they need to do, I guess.

At least they’re focusing a bit: they promise to tell us about the genetics of hand development, and specifically of the thumb. They’re scanning genes that are different between humans and chimpanzees, looking for molecules that suggest they play a role in the differences in digits. A gene is found that is active in the thumb and big toe, and also differs significantly in sequence between us and the chimps. This is work I’m unfamiliar with — it would be nice if they named the gene for us!

Noooo…we’re teased with some interesting work, and now it’s flitting off to talk about the brain.

Another tease: a researcher identifies a gene that differs between humans and chimpanzees, and is defective in humans; it’s involved in chewing muscles. It is suggested that knocking out this gene was part of the process of freeing up the expansion of the cranium. It’s a frustrating part of the medium that it makes it hard to dig up more specific citations. (OK, here’s a short article on Stedman’s work).

They do it again with a regulator of neuronal growth involved in microcephaly: name the gene, please. They keep talking around it, calling it “this gene” or “the key gene”. It’s just odd that they ignore one of the conventions of molecular biology, failing to give us a name that we can use as a handle. It’s going to make it difficult to talk about over the water cooler tomorrow, isn’t it?

Olivia Judson relates it all back to Darwin: he was the beginning, not the end of evolutionary biology.

My opinion overall: the first half hour was boring to me — it was an extremely basic primer in old-school Darwinian biology. The middle hour was of more interest, and did get into real evolutionary developmental biology, and showed off some of the best examples of work in the field. This was the bit I’d find most useful in my classes; that first half-hour was too basic for most freshman biology majors.

I wasn’t too keen on the last bit where it got very human-centric, but I can see where the examples they talked about would provoke viewer interest. I just wish it were possible for the medium to push a little deeper into the topics than they did.

Carroll, Shubin, and Tabin were good. Make them TV stars!

α-actinin evolution in humans

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Perhaps your idea of the traditional holiday week involves lounging about with a full belly watching football — not me, though. I think if I did, I’d be eyeing those muscular fellows with thoughts of muscle biopsies and analyses of the frequency of α-actinin variants in their population vs. the population of national recliner inhabitants. I’m sure there’s an interesting story there.

In case you’re wondering what α-actinin is, it’s a cytoskeletal protein that’s important in anchoring and coordinating the thin filaments of actin that criss-cross throughout your cells. It’s very important in muscle, where it’s localized in the Z-disk at the boundaries of sarcomeres, the repeated contractile units of the muscle. This diagram might help you visualize it:

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Actin (green), myosin (red). Rod-like tropomyosin molecules (black lines). Thin filaments in muscle sarcomeres are anchored at the Z-disk by the cross-linking protein α-actinin (gold) and are capped by CapZ (pink squares). The thin-filament pointed ends terminate within the A band, are capped by tropomodulin (bright red). Myosin-binding-protein C (MyBP-C; yellow transverse lines).

The most prominent elements in the picture are the thin filaments (made of actin) and thick filaments (made of myosin) which slide past each other, driven by motor proteins, to cause contraction and relaxation of the muscle. The α-actinin proteins are the subtle orange lines in the Z disks on the left and right.

The α-actinin proteins are evolutionarily interesting. In vertebrates, there are usually four different kinds: α-actinin 1, 2, 3, and 4. 1 and 4 are ubiquitous in all cells, since all cells have a cytoskeleton, and the α-actinins are important in anchoring the cytoskeleton. α-actinin-2 and -3 are the ones of interest here, because they are specifically muscle actinins. α-actinin-2 is found in all skeletal muscle fibers, cardiac muscle, and also in the brain (no, not muscle in the brain, there isn’t any: in the cytoskeleton of neurons). Just to complicate matters a bit, α-actinin-2 is also differently spliced in different tissues, producing a couple of isoforms from a single gene. α-actinin-3 is not found in the brain or heart, but only in skeletal muscle and specifically in type II fast glycolytic muscle fibers.

Muscle fibers are specialized. Some are small diameter, well vascularized, relatively slow fibers that are optimized for endurance; they can keep contracting over and over again for long periods of time. These are the fibers that make up the dark meat in your Christmas turkey or duck. Other fibers are large diameter, operate effectively anaerobically, and are optimized for generating lots of force rapidly, but they tend to fatigue quickly — and there are more of these in the white meat of your Christmas bird. (There are also intermediate fiber types that we won’t consider here.) Just keep these straight in your head to follow along: the fast type II muscle fibers are the ones that you use to generate explosive bursts of force, and may be enriched in α-actinin-3; the slower fibers are the ones you use to keep going when you run marathons, and contain α-actinin-2. (There are other even more important differences between fast and slow fibers, especially in myosin variants, so differences in α-actinins are not major determinants of muscle type.)

Wait, what about evolution? It turns out that invertebrates only have one kind of α-actinin, and vertebrates made their suite of four in the process of a pair of whole genome duplications. We made α-actinin-2 and -3 in a duplication event roughly 250-300 million years ago, at which time they would have been simple duplicates of each other, but they have diverged since then, producing subtle (and not entirely understood) functional differences from one another, in addition to acquiring different sites of expression. α-actinin-2 and -3 in humans are now about 80% identical in amino acid sequence. What has happened in these two genes is consistent with what we know about patterns of duplication and divergence.

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Using sarcomeric α-actinin as an example, after duplication of a gene capable of multiple interactions/functions, there are two possible distinct scenarios besides gene loss. A: Sub-functionalisation, where one interaction site is optimised in each of the copies. B: Neo-functionalisation, where one copy retains the ancestral inter- action sites while the other is free to evolve new interaction sites.

So what we’re seeing in the vertebrate lineage is a conserved pattern of specialization of α-actinin-3 to work with fast muscle fibers — it’s a factor in enhancing performance in the specific task of generating force. The α-actinin-3 gene is an example of a duplicated gene becoming increasingly specialized for a particular role, with both changes in the amino acid sequence that promoted a more specialized activity, and changes in the regulatory region of the gene so that it was only switched on in appropriate muscle fibers.

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Duplication and divergence model proposed by this paper. Before duplication the ancestral sarcomeric α-actinin had the functions of both ACTN2 and ACTN3 in terms of tissue expression and functional isoforms. After duplication, ACTN2 has conserved most of the functions of the preduplicated gene, while ACTN3 has lost many of these functions, which may have allowed it to optimise function in fast fibres.

That’s cool, but what we need is an experiment: we need to knock out the gene and see what happens. Mutations in α-actinin-2 are bad—they cause a cardiomyopathy. Losing α-actinin-4 leads to serious kidney defects (that gene is expressed in kidney tissue). What happens if we lose α-actinin-3?

It turns out you may be a guinea pig in that great experiment. Humans acquired a mutation in the α-actinin-3 gene, called R577X, approximately 40-60,000 years ago, and this mutation is incredibly common: about 50% of individuals of European and Asian descent carry it, and about 10% of individuals from African populations. Furthermore, an analysis of the flanking DNA shows relatively little recombination or polymorphism — which implies that the allele has reached this high frequency relatively recently and rapidly, which in turn implies that there has been positive selection for a nonsense mutation that destroys α-actinin-3 in us. The data suggests that a selective sweep for this variant began in Asia about 33,000 years ago, and in Europe about 15,000 years ago.

There is no disease associated with the loss of α-actinin-3. It seems that α-actinin-2 steps up to the plate and fills the role in type II fast muscle fibers, so everything functions just fine. Except…well, there is an interesting statistical effect.

The presence of a functional α-actinin-3 gene is correlated with athletic performance. A study of the frequency of the R577X mutation in athletes and controls found that there is a significant reduction in the frequency of the mutation among sprinters and power-lifters. At the Olympic level, none of the sprinters in the sample (32 individuals) carried the α-actinin-3 deficiency. Among Olympic power lifters, all had at least one functional copy of α-actinin-3.

Awesome. Now I’m wondering about my α-actinin-3 genotype, and whether I have a good biological excuse for why I always got picked last for team sports in high school gym class. This is also why I’m interested in taking biopsies of football players…both for satisfying a scientific curiosity, and for revenge.

You may be wondering at this point about something: α-actinin-3 has a clear beneficial effect in enhancing athletic performance, and its conservation in other animal species suggests that it’s almost certainly a good and useful protein. So why has there been positive selection (probably) for a knock-out mutation in the human lineage?

There is a weak correlation in that study of athletic performance that high-ranking athletes in endurance sports have an increased frequency of the R577X genotype; it was only seen in female long-distance runners, though. More persuasive is the observation that α-actinin-3 knockouts in mice also produced a shift in metabolic enzyme markers that are indicative of increased endurance capacity. The positive advantage of losing α-actinin-3 may be more efficient aerobic metabolism in muscles, at the expense of sacrificing some strength at the high end of athletic performance.

This is yet another example of human evolution in progress—we’re seeing a shift in human muscle function over the course of a few tens of thousands of years.

Lek M, Quinlan KG, North KN (2009) The evolution of skeletal muscle performance: gene duplication and divergence of human sarcomeric alpha-actinins. Bioessays 32(1):17-25. [Epub ahead of print]

MacArthur DG, Seto JT, Raftery JM, Quinlan KG, Huttley GA, Hook JW, Lemckert FA, Kee AJ, Edwards MR, Berman Y, Hardeman EC, Gunning PW, Easteal S, Yang N, North KN (2007) Loss of ACTN3 gene function alters mouse muscle metabolism and shows evidence of positive selection in humans. Nat Genet.39(10):1261-5.

Yang N, MacArthur DG, Gulbin JP, Hahn AG, Beggs AH, Easteal S, North K (2003) ACTN3 genotype is associated with human elite athletic performance. Am J Hum Genet 73(3):627-31.

Teaching Your Inner Fish

Next Fall, I’ll be back in the classroom teaching introductory biology again. One thing I’m planning to do is to use Shubin’s Your Inner Fish for that course…and just look what the good man has done just for me: all the figures from the book have been released as powerpoint slides.

OK, he probably didn’t think about me at all, and he’s releasing them for everyone to use, but still…it’s awfully serendipitous.

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Grab ’em all, teachers! These are tools for getting more evolution into the biology classroom!

Evolving fish of the lower Congo

The lower Congo river is deep and complex, and there are a surprising number of hydrologic features that act as barriers separating populations of fish — this very nice video explains the diversity of species and the ongoing evolution of the fish in this environment.

They too briefly showed a blind depigmented cichlid that apparently lives in very deep troughs in the river — I wanted to see more about that. It’s probably out of the question to send divers down into that maelstrom, but cameras? Someday? Please?

Oldie moldies that are pretty darned fascinating

The Royal Society of London is releasing free pdfs of some of its best-known papers — and we’re talking real classics. Check out their timeline which lets you scan for papers in chronological order; the oldest are a pair for 1666-1667 by Robert Boyle and Robert Hook(e), which will horrify modern audiences: they describe experiments in blood transfusions and examinations of the lungs in dogs. I would not have wanted to be a dog in 17th century London, that’s for sure.

One that is particularly interesting is this account of a new technique in preventative medicine from 1736: “An Account of Inoculation by Sir Hans Sloane, Bart. Given to Mr. Ranby, to be Published, Anno 1736. Communicated by Thomas Birch, D. D. Secret. R. S.” It describes the use of small pox vaccinations, and contains this prescient closer:

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He’s using “wonderful” in an archaic sense of “strange and astonishing”. And isn’t it strange that still today we have people fighting vaccination through “dread of other diſtempers being inculcated with it, and other unreaſonable prejudices”?

My favorite paper of the bunch, and the one that ought to be required reading for biologists, is The Spandrels of San Marco and the Panglossian Paradigm: A Critique of the Adaptationist Programme”. If you haven’t read it yet, you should…maybe right after you finish browsing the collection of olde curiosities on that page.

Get your geek on for Thursday

I’m going to be opening my mouth again on Thursday in Minneapolis — I’ll be giving a talk in MCB 3-120 on the Minneapolis campus at 7:30 on Thursday, 3 December. This will be open to the public, and it will also be an all-science talk, geared for a general audience. I’d say they were going to check your nerd credentials at the door, but just showing up means you’re already fully qualified.

The subject of the talk is my 3 big interests: a) evolution, or how we got here over multiple generations, b) development, or how we got here in a single generation, and c) the nervous system, the most complicated tissue we have. I intend to give a rough outline of how nervous tissue works, how it is assembled into a working brain, and how something so elaborate could have evolved. All in one hour. Wheee!

Afterwards, we’ll be joining the CASH gang for refreshments, somewhere. They haven’t told me yet where, but I know they’re fond of pizza.

IGERT2009: Sunday morning session

My little laptop is functional again, so at least I’ll be able to blog these Sunday morning IGERT sessions in real-time. I still have to transcribe my notes from yesterday; I’ll plan on getting that done on the plane this afternoon.

Kristi Montooth: Mitochondrial-nuclear epistasis for metabolic fitness in flies

How do physiological systems evolve to maintain metabolic fitness? This is a process that involves interactions between two genomes, the nuclear and mitochondrial. Energy metabolism is important and is the target of mutation, but the same players are found all across the tree of life, suggesting that there is also strong selective pressure to maintain a common system.

Montooth is looking at inducible gene expression: is there an energetic cost to switch genes off and on? She’s using respirometers that can measure the metabolic rate of single flies or larva. Flies are subjected to heat shock, which switches on HSP70. Flies normally have 6 copies of HSP70; they have mutants with 12, and they show a much greater rise in metabolic rate in response to heat shock.

Mitochondria are the source of the energy for this response. Mitochondria also have a high mutation rate and show strong linkage (no sexual recombination to cover for errors that arise). She’s arguing for selection for compensatory evolution in the nuclear genome, and the accumulation of intergenomic epistasis. To dissect the effects of coevolution of mitochondria and nuclear genomes, she transplanted mitochondria from different species into Drosophila melanogaster. These have between 18 and 100 amino acid substitutions from the Dmel sequence.

She plots mitochondrial genome in order of increasing divergence against measured fitness (she used a competition assay that she did not describe in detail). There is no correlation seen at all. Also, high fitness X/mtDNA genotypes in one sex can be low fitness genotypes in the other sex. Interactions between the X and mtDNA can maintain variation in both genomes. All of the fitness effects, with one exception, are subtle.

Some of the transgenomic effects have very strong effects on female fecundity, developmental rates, and locomotion. But adult metabolic rate shows no difference! The idea is that there are lots of homeostatic mechanisms that maintain metabolism very tightly, which then have secondary effects.

Johanna Schmitt: Adaptive evolution of Arabidopsis flowering pathways in different climates

Schmitt does ecological development, looking at the timing of plant development in different environments. How does phenology respond and adapt to climate variation? We expect evolution to adapt to variation in seasonal timing. The signaling pathways in Arabidopsis are well known; they respond to hormones, photoperiod, and ambient temperature by way of a fairly complicated set of pathways she showed us in a slide…sorry, no way I can reproduce it here!

Across its range, it shows a great deal of life history variation; one pattern in the Mediterranean, another in colder northern climes, and yet another in Northern Scandinavia, varying in how much time they spend in vegetative rosettes vs. bolting and flower production. Questions: are there are genetic variants associated with different life history patterns, can they identify the genes, and can they perturb them?

The experiments involved massive plantings in different sites in Europe with different climates, with different mutants. Is natural variation in candidate genes involved in variation in flowering time? They studied FRIGIDA, a gene that effects the vernalization pathway. When you lose FRIGIDA, you should see much more rapid flowering. Loss of function in this gene has evolved multiple times in northwestern Europe. The effect depends on the timing of planting and climate.

The effect of the mutant varies across geography, and they have a photothermal model of flowering time. The plants are tracking light and temperature, and the different mutants are counting up these inputs in slightly different ways. They can use this model to make predictions on the effects of FRIGIDA on flowering time with changes in germination timing, and then test these in the next year with plantings at different times and in their different geographical sites, and the model is working accurately.

They are also plugging in predicted future climate change from NOAA, and asking what we can expect to see 100 years from now; she showed maps of expected flowering times in 2100. They are also making predictions of the expected distributions of FRIGIDA alleles over time, and they hope to do the same for many other alleles in Arabidopsis.

Artyom Kopp: How the fly got its sexy legs – the origin and evolution of Drosophila sex combs

The sex comb is a male specific structure on the front legs which most Drosophila species lack — it’s a fairly recent innovation. How do you evolve a novel structure?

It’s limited to the melanogaster and obscura species groups, with quite a bit of diversity in different species, varying from 2-50 teeth, location, and arrangement. How do you go from sexually monomorphic state of a generically hairy leg to one with a specific bristle arrangement in males? The sex comb in males is homologous to a subset of bristles also found in females; in males, that patch of epidermis rotates 90° and the bristles enlarge. He showed a very pretty developmental series of this epithelium undergoing cell shape changes that move the bristles to a new location. Other species show similar morphological remodeling, but sometimes with some significant differences: D. kikkawai doesn’t do the rotation, but instead the bristle precursors arise in their final position. These modes do not cluster together phylogenetically, so these are examples of convergent evolution, generating similar structures with different mechanisms.

They are taking apart the genetics and regulatory inputs of sex comb development. Basically, it involves just about everything. It seems to arise by an interaction between Hox and sex determination genes. Spatial modulation of Sex combs reduced controls sex comb position. Scr in pupa; stages is only expressed in a limited domain in the leg, and ectopic expression of Scr produces multiple sex combs. Expression is also sexually dimorphic, with no upregulation of Scr in female legs. In D. ficusphila, which has enormous sex combs, Scr levels are elevated yet further to 7 times the levels found in D. willistoni.

The sex determination gene Double sex is also spatially patterned, and is refined and elevated to high levels in the area around the developing sex combs. Ectopic expression of Dsx induces ectopic sex combs.

How can a new developmental pathway evolve? In the ancestral condition, Scr is controlled by spatial cues to produce segmental patterns of bristles; in the sex-comb carrying species, Scr is coupled to Dsx. This explains the spatial pattern of gene expression, but it also needs to acquire new downstream targets to, for instance, regulate epidermal rotations.

Drosophila are old, and many of these species differences are millions of years old. They are now looking at more recently diverged species with differences in sex comb morphology, and are looking for correlations between Scr and species divergence.

And with that, I have to run for the airport shuttle. Good talks, and I unfortunately have to miss Rudy Raff’s wrap-up of the meeting.

A creationist at the Chicago meeting

Last week, I described the lectures I attended at the Chicago 2009 Darwin meetings (Science Life also blogged the event). Two of the talks that were highlights of the meeting for me were the discussions of stickleback evolution by David Kingsley and oldfield mouse evolution by Hopi Hoekstra — seriously, if I were half my age right now, I’d be knocking on their doors, asking if they had room for a grad student or post-doc or bottle-washer. They are using modern techniques in genetics and molecular biology to look at variation in natural populations in the wild, and working out the precise genetic changes that led to the evolution of differences in development and morphology. They are doing stuff that, back when I actually was a graduate student, would have been regarded as technically impossible; you needed model systems in the laboratory to have the depth of molecular information required to track down the molecular basis of novel morphs, and you couldn’t possibly just grab some interesting but otherwise unknown species out on a beach or a pond and work out a map and localize genetic differences between individuals. They’re doing it now, though, and making it look easy.

Then there were all the other talks in population genetics and paleontology (and the talks on history and philosophy, which I almost entirely neglected)…this was a meeting that everywhere demonstrated major advances in our understanding of evolution. Every talk was about the successes of evolutionary theory and directions to take to overcome incomplete areas of understanding; this was a wonderfully positive and promising event that should have impressed all the attendees with the quality of the work that has been done and the excitement of the potential for future research. Like I said, there were a whole bunch of people here that I want to be when I grow up.

Well, normal people would feel that way. Paul Nelson, that creationist, was also there. Nelson is a weird guy; he’s always hanging around the edges of these scientific meetings, and you’d think that after all these years of lurking, he’d actually learn something, but no…the only skill he has mastered is the art of ignoring what he doesn’t like and incorporating fragments of sentences into his armor of ignorance. It’s very sad.

I talked with Nelson briefly at a reception at the meetings, and we both agreed on the quality of Kingsley’s work — but that’s about all. Nelson thought it supported ID better than neo-Darwinian evolutionary theory. His argument was that a) all anybody ever described was loss of features, and b) a large parent population was the source of all the allelic variation in the sub-populations studied, which is what ID predicts. He didn’t mention their favorite magic word of “front-loading”, but I could see what he was thinking.

How Nelson can hang about on the fringes of the evo-devo world and not notice that what was described by modern empirical research is exactly what the evo-devo theoreticians expected is a mystery — these were results that fit beautifully what science, not the wishful voodoo of intelligent design creationism, predicts.

Both Kingsley and Hoekstra are looking at recent species, subpopulations that separated from parent populations within the last ten thousand years, and have adapted relatively rapidly to new environmental conditions. The sticklebacks are fragments of marine species that were isolated in freshwater streams and lakes, while the beach mice are parts of a widespread population of oldfield mice that are adapting to gulf coast islands. They are also working with populations that can be bred back to the root stock, that retain the ability to do genetic crosses, so of course the variation is not on the magnitude of turning fins into limbs (we need large amounts of geological time to do that; it’s the kind of work Neil Shubin would do, and unfortunately, he can’t cross Tiktaalik with Acanthostega). Complaining that the variants the real scientists are looking at aren’t the kind that the creationists want is a particularly clueless kind of whine, since the scientists are intentionally focusing on the variants that are amenable to dissection by their techniques.

The other aspect of their work that confirms evo-devo expectations is that what they’re discovering is that the genetic mechanisms behind morphological variants are changes in regulatory DNA — that what’s happening is that regulatory genes like Pitx1 or Mc1r are being switched off or on. We anticipate that a lot of morphological novelty is going to be generated by switching genes off and on, and by recombination of patterns of gene expression. Nelson and Behe are reduced to carping on the sidelines that observed variants are just the product of getting large effects by trivially flipping switches, while all the real biologists are out there in the middle of the work happily announcing that we can get large-scale morphological effects by simply flipping switches, and hey, isn’t that cool, and doesn’t that tell us a lot about the origins of evolutionary novelties? It’s not just a to-may-to/to-mah-to difference in interpretation, this is a case of the creationists wilfully and ignorantly missing the whole point of an exciting line of research.

There’s also a fundamental failure of comprehension. Creationists see loss of a feature like pelvic spines, or a reduction in pigmentation, and declare that the evolutionary evidence is “all breaking things and losing things”. Wrong. What we have here is a complete lack of understanding of developmental genetics. What we typically find are changes in the pattern of expression of developmental genes, not wholesale losses. In the stickleback, Pitx1 is still there; what’s different is that the places in the embryo where it is turned on have changed, the map of the pattern of gene expression has shifted. You cannot describe that as simply a broken gene. Similarly, in the mouse, Hoekstra showed that the expression of genes that reduce pigmentation has expanded. We’ve seen the same thing in the blind cavefish; a creationist looks at it and says it’s just broken and has lost its eyes, but the scientists look closer and see that no, the fish have actually increased gene expression and expanded the domain of a midline gene.

Just wait for the detailed analysis of jaw morphology in cichlid fishes. These animals have radically different variants in feeding structures, which is thought to be the root of their adaptability and the radiation of different forms, and I guarantee you that the creationists will ignore the morphological novelties and focus on the fact that to achieve that, some genes will be downregulated (I also guarantee you that there will be such shifts in expression). It’s “all breaking things and losing things”, after all; just like baking a cake involves breaking eggs.

I don’t know how the creationists fit known variations in the coding sequences of genes (how do you translate a single-nucleotide polymorphism into their vision of all change being a matter of losses?) into their idea that all evolution is a matter of breaking DNA, or how they can claim all novelty requires a designer when people can track the progression of morphological shifts in the tetrapod transition, for instance, across tens of millions of years. It seems to be their desperate 21st century excuse in the face of the overwhelming progression of information from 21st century biological science.

Nelson ends his skewed summary of the meeting with the comment that “It’s a heck of a lot of fun to attend a conference like this, if you don’t mind being the butt of jokes.” I’m sure. I suppose Nelson could have even more fun if he put on a dunce cap and drooled a lot, because that’s basically his role at these meetings anyway — he’s the butt of jokes because he shows up and then happily demonstrates his ignorance about what’s going on. It’s not a role I’d enjoy, but the gang at the clown college called the Discovery Institute have a slightly different perspective, I suppose.