Design flaws support evolution

This is a nicely done lecture on design flaws in our anatomy and physiology, to refute claims of intelligent design.

Part 2 Part 3

I know exactly how creationists will reply, though, since I’ve heard it often enough. She’s making a theological argument, they’ll say, claiming to know God’s intent and making an assumption of his goals. It will be a restatement of the old chestnut, “God works in mysterious ways.”

However, that’s not the argument here. Imperfections and sub-optimal properties are an outcome of evolutionary theory; this is a positive argument that observations of the world best fit a model positing a history of accidents and refinements constrained along lines of descent. If the creationists want to complain, they first have to propose a set of predictions that would discriminate between accident and design, and starting from a god who can do anything at any whim is not a fruitful source of hypotheses.

How to make a snake

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First, you start with a lizard.

Really, I’m not joking. Snakes didn’t just appear out of nowhere, nor was there simply some massive cosmic zot of a mutation in some primordial legged ancestor that turned their progeny into slithery limbless serpents. One of the tougher lessons to get across to people is that evolution is not about abrupt transmutations of one form into another, but the gradual accumulation of many changes at the genetic level which are typically buffered and have minimal effects on the phenotype, only rarely expanding into a lineage with a marked difference in morphology.

What this means in a practical sense is that if you take a distinct form of a modern clade, such as the snakes, and you look at a distinctly different form in a related clade, such as the lizards, what you may find is that the differences are resting atop a common suite of genetic changes; that snakes, for instance, are extremes in a range of genetic possibilities that are defined by novel attributes shared by all squamates (squamates being the lizards and snakes together). Lizards are not snakes, but they will have inherited some of the shared genetic differences that enabled snakes to arise from the squamate last common ancestor.

So if you want to know where snakes came from, the right place to start is to look at their nearest cousins, the lizards, and ask what snakes and lizards have in common, that is at the same time different from more distant relatives, like mice, turtles, and people…and then you’ll have an idea of the shared genetic substrate that can make a snake out of a lizard-like early squamate.

Furthermore, one obvious place to look is at the pattern of the Hox genes. Hox genes are primary regulators of the body plan along the length of the animal; they are expressed in overlapping zones that specify morphological regions of the body, such as cervical, thoracic, lumbar, sacral/pelvic, and caudal mesodermal tissues, where, for instance, a thoracic vertebra would have one kind of shape with associated ribs, while lumbar vertebra would have a different shape and no ribs. These identities are set up by which Hox genes are active in the tissue forming the bone. And that’s what makes the Hox genes interesting in this case: where the lizard body plan has a little ribless interruption to form pelvis and hindlimbs, the snake has vertebra and ribs that just keep going and going. There must have been some change in the Hox genes (or their downstream targets) to turn a lizard into a snake.

There are four overlapping sets of Hox genes in tetrapods, named a, b, c, and d. Each set has up to 13 individual genes, where 1 is switched on at the front of the animal and 13 is active way back in the tail. This particular study looked at just the caudal members, 10-13, since those are the genes whose expression patterns straddle the pelvis and so are likely candidates for changes in the evolution of snakes.

Here’s a summary diagram of the morphology and patterns of Hox gene expression in the lizard (left) and snake (right). Let’s see what we can determine about the differences.

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Evolutionary modifications of the posterior Hox system in the whiptail lizard and corn snake. The positions of Hox expression domains along the paraxial mesoderm of whiptail lizard (32-40 somites, left) and corn snake (255-270 somites, right) are represented by black (Hox13), dark grey (Hox12), light grey (Hox11) and white (Hox10) bars, aligned with coloured schemes of the future vertebral column. Colours indicate the different vertebral regions: yellow, cervical; dark blue, thoracic; light blue, lumbar; green, sacral (in lizard) or cloacal (in snake); red, caudal. Hoxc11 and Hoxc12 were not analysed in the whiptail lizard. Note the absence of Hoxa13 and Hoxd13 from the corn snake mesoderm and the absence of Hoxd12 from the snake genome.

The morphology is revealing: snakes and lizards have the same regions, cervical (yellow), thoracic (blue), sacral (or cloacal in the snake, which lacks pelvic structures in most species) in green, and caudal or tail segments (red). The differences are in quantity — snakes make a lot of ribbed thoracic segments — and detail — snakes don’t make a pelvis, usually, but do have specializations in that corresponding area for excretion and reproduction.

Where it really gets interesting is in the expression patterns of the Hox genes, shown with the bars that illustrate the regions where each Hox gene listed is expressed. They are largely similar in snake and lizard, with boundaries of Hox expression that correspond to transitions in the morphology of vertebrae. But there are revealing exceptions.

Compare a10/c10 in the snake and lizard. In the snake, these two genes have broader expression patterns, reaching up into the thoracic region; in the lizard, they are cut off sharply at the sacral boundary. This is interesting because in other vertebrates, the Hox 10 group is known to have the function of suppressing rib formation. Yet there they are, turned on in the posterior portion of the thorax in the snake, where there are ribs all over the place.

In the snake, then, Hox a10 and c10 have lost a portion of their function — they no longer shut down ribs. What is the purpose of the extended domain of a10/c10 expression? It may not have one. A comparison of the sequences of these genes between various species reveals a detectable absence of signs of selection — the reason these genes happen to be active so far anteriorly is because selection has been relaxed, probably because they’ve lost that morphological effect of shutting down ribs. Those big bars are a consequence of simple sloppiness in a system that can afford a little slack.

The next group of Hox genes, the 11 group, are very similar in their expression patterns in the lizard and the snake, and that reflects their specific roles. The 10 group is largely involved in repression of rib formation, but the 11 group is involved in the development of sacrum-specific structures. In birds, for instance, the Hox 11 genes are known to be involved in the development of the cloaca, a structure shared between birds, snakes, and lizards, so perhaps it isn’t surprising that they aren’t subject to quite as much change.

The 13 group has some notable differences: Hox a13 and d13 are mostly shut off in the snake. This is suggestive. The 13 group of Hox genes are the last genes, at the very end of the animal, and one of their proposed functions is to act as a terminator of patterning — turning on the Hox 13 genes starts the process of shutting down the mesoderm, shrinking the pool of tissue available for making body parts, so removing a repressor of mesoderm may promote longer periods of growth, allowing the snake to extend its length further during embryonic development.

So we see a couple of clear correlates at the molecular level for differences in snake and lizard morphology: rib suppression has been lost in the snake Hox 10 group, and the activity of the snake Hox 13 group has been greatly curtailed, which may be part of the process of enabling greater elongation. What are the similarities between snakes and lizards that are also different from other animals?

This was an interesting surprise. There are some differences in Hox gene organization in the squamates as a whole, shared with both snakes and lizards.

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Genomic organization of the posterior HoxD cluster. Schematic representation of the posterior HoxD cluster (from Evx2 to Hoxd10) in various vertebrate species. A currently accepted phylogenetic tree is shown on the left. The correct relative sizes of predicted exons (black boxes), introns (white or coloured boxes) and intergenic regions (horizontal thick lines) permit direct comparisons (right). Gene names are shown above each box. Colours indicate either a 1.5-fold to 2.0-fold (blue) or a more than 2.0-fold (red) increase in the size of intronic (coloured boxes) or intergenic (coloured lines) regions, in comparison with the chicken reference. Major CNEs are represented by green vertical lines: light green, CNEs conserved in both mammals and sauropsids; dark green, CNEs lost in the corn snake. Gaps in the genomic sequences are indicated by dotted lines. Transposable elements are indicated with asterisks of different colours (blue for DNA transposons; red for retrotransposons).

That’s a diagram of the structure of the chromosome in the neighborhood of the Hox d10-13 genes in various vertebrates. For instance, look at the human and the turtle: the layout of our Hox d genes is vary similar, with 13-12-11-10 laid out with approximately the same distances between them, and furthermore, there are conserved non-coding elements, most likely important pieces of regulatory DNA, that are illustrated in light yellow-reen and dark green vertical bars, and they are the same, too.

In other words, the genes that stake out the locations of pelvic and tail structures in turtles and people are pretty much the same, using the same regulatory apparatus. It must be why they both have such pretty butts.

But now compare those same genes with the squamates, geckos, anoles, slow-worms, and corn snakes. The differences are huge: something happened in the ancestor of the squamates that released this region of the genome from some otherwise highly conserved constraints. We don’t know what, but in general regulation of the Hox genes is complex and tightly interknit, and this order of animals acquired some other as yet unidentified patterning mechanism that opened up this region of genome for wider experimentation.

When these regions are compared in animals like turtles and people and chickens, the genomes reveal signs of purifying selection — that is, mutations here tend to be unsuccessful, and lead to death, failure to propagate, etc., other horrible fates that mean tinkering here is largely unfavorable to fecundity (which makes sense: who wants a mutation expressed in their groinal bits?). In the squamates, the evidence in the genome does not witness to intense selection for their particular arrangement, but instead, of relaxed selection — they are generally more tolerant of variations in the Hox gene complex in this area. What was found in those enlarged intergenic regions is a greater invasion of degenerate DNA sequences: lots of additional retrotransposons, like LINES and SINES, which are all junk DNA.

So squamates have more junk in the genomic trunk, which is not necessarily expressed as an obvious phenotypic difference, but still means that they can more flexibly accommodate genetic variations in this particular area. Which means, in turn, that they have the potential to produce more radical experiments in morphology, like making a snake. The change in Hox gene regulation in the squamate ancestor did not immediately produce a limbless snake, instead it was an enabling mutation that opened the door to novel variations that did not compromise viability.

Di-Po N, Montoya-Burgos JI, Miller H, Pourquie O, Milinkovitch MC, Duboule D (2010) Changes in Hox genes’ structure and function during the evolution of the squamate body plan. Nature 464:99-103.

Fodor and Piattelli-Palmarini get everything wrong

People who don’t understand modern evolutionary theory shouldn’t be writing books criticizing evolutionary theory. That sounds like rather pedestrian and obvious advice, but it’s astonishing how often it’s ignored — the entire creationist book publishing industry demands a steady supply of completely clueless authors who think their revulsion at the implications of Darwinian processes is sufficient to compensate for their ignorance. And now Jerry Fodor and Massimo Piattelli-Palmarini, a philosopher and a cognitive scientist, step up to the plate with their contribution to this genre of uninformed folly.

I haven’t read their book, What Darwin Got Wrong, and I don’t plan to; they’ve published a brief summary in New Scientist (a magazine that is evolving into a platform for sensationalistic evolution-deniers, sad to say), and that was enough. It’s breathtaking in its foolishness, and is sufficient to show the two authors are parading about quite nakedly unashamed of their lack of acquaintance with even the most rudimentary basics of modern evolutionary biology.

In our book, we argue in some detail that much the same [they are comparing evolution to Skinner’s behaviorism] is true of Darwin’s treatment of evolution: it overestimates the contribution the environment makes in shaping the phenotype of a species and correspondingly underestimates the effects of endogenous variables. For Darwin, the only thing that organisms contribute to determining how next-generation phenotypes differ from parent-generation phenotypes is random variation. All the non-random variables come from the environment.

Suppose, however, that Darwin got this wrong and various internal factors account for the data. If that is so, there is inevitably less for environmental filtering to do.

I am entirely sympathetic with the argument that naive views of evolution that pretend that populations are infinite plastic and can respond to almost any environmental demand, given enough time, are wrong. I appreciate a good corrective to the excesses of adaptationism; evolution is much more interesting and diverse than the kind of simplistic whetstone it is too often reduced to, but we don’t need bad critiques that veer off into the lunacy of selection-denial. It’s also literally true that Darwin was completely wrong on the basic mechanisms of inheritance operating in organisms — he didn’t know about genes, postulated the existence of distributed information about the organization of tissues and organs that was encapsulated in unobserved mystery blobs called “gemmules” that migrated from the arm, for instance, to the gonads, to pass along instructions on how to build an arm to the gametes. Telling us that Darwin got the chain of information wrong is nothing new or interesting.

It also gets the problem backwards. Darwin’s proposed mechanism actually supported the idea of the inheritance of acquired characters, and as Fodor wants to argue, encouraged the idea that organisms were more responsive to environmental effects than they actually are. The neo-Darwinian synthesis melded the new science of genetics with evolutionary theory, and did make “various internal factors” much more important. They’re called genes.

What do you get when authors who know nothing about genetics and evolution write about genetics and evolution?

This is what makes Fodor and Piattelli-Palmarini’s ideas so embarrassingly bad. They seem to know next to nothing about genetics, and so when they discover something that has been taken for granted by scientists for almost a century, they act surprised and see it as a death-stroke for Darwinism. It’s rather like reading about the saltationist/biometrician wars of the early 1900s, when Mendel was first rediscovered and some people argued that the binary nature of the ‘sports’ described in analyses of inheritance meant the incremental changes described by Darwin were impossible. The ‘problems’ were nonexistent, and were a product merely of our rudimentary understanding of genetics — it was resolved by eventually understanding that most characters of an organism were the product of many genes working together, and that some mutations do cause graded shifts in the phenotype.

Here, for instance, is one of their astonishing revelations about the nature of inheritance:

Darwinists say that evolution is explained by the selection of phenotypic traits by environmental filters. But the effects of endogenous structure can wreak havoc with this theory. Consider the following case: traits t1 and t2 are endogenously linked in such a way that if a creature has one, it has both. Now the core of natural selection is the claim that phenotypic traits are selected for their adaptivity, that is, for their effect on fitness. But it is perfectly possible that one of two linked traits is adaptive but the other isn’t; having one of them affects fitness but having the other one doesn’t. So one is selected for and the other “free-rides” on it.

That is so trivially true that it is a good point to make if you are addressing somebody who is biologically naive, and I think it is a valuable concept to emphasize to the public. But this is Fodor and Piattelli-Palmarini chastising biologists with this awesome fact as if we’ve been neglecting it. It’s baffling. Linkage is a core concept in genetics; Alfred Sturtevant and Thomas Morgan worked it out in about 1913, and it’s still current. The genographic project, which is trying to map out the history of human populations, uses haplotype data — clusters of alleles tend to stay clumped together, only occasionally broken up by recombination, so their arrangements can be used as markers for geneology. The default assumption is that these sets of alleles are not the product of selection, but of chance and history!

They might also look up the concepts of linkage disequilibrium and epistasis. Are we already aware of “free-riding,” background effects, and interactions between genes? Yes, we are. Do we think every trait in every individual is the product of specific selection? You might be able to find a few weird outliers who insist that they are, and perhaps more who regard that as a reasonable default assumption to begin an analysis, but no, it’s obvious that it can’t be true.

It also should be obvious that a fact of genetics that has been known for almost a century and that was part of the neo-Darwinian synthesis from the very beginning isn’t going to suddenly become a disproof of the synthesis when belatedly noticed by a philosopher and neuroscientist in the 21st century.

This time it’s personal: abusing evo-devo

As bad as building an argument on the faulty premise of ignorance might be, there’s another approach that Fodor and Piattelli-Palmarini take that is increasingly common, and personally annoying: the use of a growing synthesis of evolutionary ideas with developmental biology to claim that evolution is dead. This is rather like noting that the replacement of carburetors with electronic fuel injection systems means that internal combustion engines are about to be extinct — evo-devo is a refinement of certain aspects of biology that has, we think, significant implications for evolution, especially of multicellular organisms. It is not a new engine. People who claim it is understand neither development nor evolution.

Fodor and Piattelli-Palmarini throw around a few buzzwords that tell me right away where they’re coming from: they’re jumping on that strange structuralist bandwagon, the one that shows some virtue when the likes of Brian Goodwin are arguing for it, but is also prone to appealing to crackpots like Pivar and Fleury and the ridiculous Suzan Mazur…and now, Fodor and Piattelli-Palmarini.

The consensus view among neo-Darwinians continues to be that evolution is random variation plus structured environmental filtering, but it seems the consensus may be shifting. In our book we review a large and varied selection of non-environmental constraints on trait transmission. They include constraints imposed “from below” by physics and chemistry, that is, from molecular interactions upwards, through genes, chromosomes, cells, tissues and organisms. And constraints imposed “from above” by universal principles of phenotypic form and self-organisation — that is, through the minimum energy expenditure, shortest paths, optimal packing and so on, down to the morphology and structure of organisms.

It’s a shame, too, because there really is some beautiful work done by the structuralist pioneers — this is a field that combines art and mathematics, and has some truly elegant theoretical perspectives. I read the paragraph above and knew instantly what they are referring to — the work of D’Arcy Wentworth Thompson. This D’Arcy Wentworth Thompson:

For the harmony of the world is made manifest in Form and Number, and the heart and soul and all the poetry of Natural Philosophy are embodied in the concept of mathematical beauty.

Ah, but I love Thompson. He wrote the best developmental biology book ever, On Growth and Form, the one that will make you think the most if you can get past the flowery prose (or better yet, enjoy the flowery prose) and avoid throwing it against the wall with great force. It’s another hundred-year-old (almost) book, you see, and Thompson never quite grasped the idea of genes.

The summary I read doesn’t mention the name Thompson even once, but I can see him standing tall in the concepts Fodor is crowing over. My inference was confirmed in a review by Mary Midgley (who, it has rumored, has actually written some sensible philosophy…but every time I’ve read her remarks on biology, comes across as a notable pinhead).

Besides this — perhaps even more interestingly — the laws of physics and chemistry themselves take a hand in the developmental process. Matter itself behaves in characteristic ways which are distinctly non-random. Many natural patterns, such as the arrangement of buds on a stem, accord with the series of Fibonacci numbers, and Fibonacci spirals are also observed in spiral nebulae. There are, moreover, no flying pigs, on account of the way in which bones arrange themselves. I am pleased to see that Fodor and Piattelli Palmarini introduce these facts in a chapter headed “The Return of the Laws of Form” and connect them with the names of D’Arcy Thompson, Conrad Waddington and Ilya Prigogine. Though they don’t actually mention Goethe, that reference still rightly picks up an important, genuinely scientific strand of investigation which was for some time oddly eclipsed by neo-Darwinist fascination with the drama of randomness and the illusory seductions of simplicity.

Her whole review is like that; she clearly adores the fact that those biologists are getting taken down a peg or two, and thinks it delightful that poor long-dead Thompson is the stiletto used to take them out. I’ve got a few words for these clowns posturing on the evo-devo stage.

D’Arcy Wentworth Thompson was wrong.

Elegantly wrong, but still wrong. He just never grasped how much of genetics explained the mathematical beauty of biology, and it’s a real shame — if he were alive today, I’m sure he’d be busily applying network theory to genetic interactions.

Let’s consider that Fibonacci sequence much beloved by poseurs. It’s beautiful, it is so simple, it appears over and over again in nature, surely it must reflect some intrinsic, fundamentally mathematical ideal inherent in the universe, some wonderful cosmic law — it appears in the spiral of a nautilus shell as well as the distribution of seeds in the head of a sunflower, so it must be magic. Nope. In biology, it’s all genes and cellular interactions, explained perfectly well by the reductionism Midgley deplores.

The Fibonacci sequence (1, 1, 2, 3, 5, 8…each term generated by summing the previous two terms) has long had this kind of semi-mystical aura about it. It’s related to the Golden Ratio, phi, of 1.6180339887… because, as you divide each term by the previous term, the ratio tends towards the Golden Ratio as you carry the sequence out farther and farther. It also provides a neat way to generate logarithmic spirals, as we seen in sunflowers and nautiluses. And that’s where the genes sneak in.

There’s an easy way to generate a Fibonacci sequence graphically, using the method of whirling squares. Look at this diagram:

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Start with a single square on a piece of graph paper. Working counterclockwise in this example, draw a second square with sides of the same length next to it. Then a third square with the same dimensions on one side as the previous two squares. Then a fourth next to the previous squares…you get the idea. You can do this until you fill up the whole sheet of paper. Now look at the lengths of each side of the squares in the series — it’s the Fibonacci sequence, no surprise at all there.

You can also connect the corners with a smooth curve, and what emerges is a very pretty spiral — like a nautilus shell.

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It’s magic! Or, it’s mathematics, which sometimes seems like magic! But it’s also simple biology. I look at the whirling squares with the eyes of a developmental biologist, and what do I see? A simple sequential pattern of induction. A patch of cells uses molecules to signal an adjacent patch of cells to differentiate into a structure, and then together they induce a larger adjacent patch, and together they induce an even larger patch…the pattern is a consequence of a mathematical property of a series expressed on a 2-dimensional sheet, but the actual explanation for why it recurs in nature is because it’s what happens when patches of cells recruit adjacent cells in a temporal sequence. Abstract math won’t tell you the details of how it happens; for that, you need to ask what are the signaling molecules and what are the responding genes in the sunflower or the mollusc. That’s where Thompson and these new wankers of the pluralist wedge fail — they stop at the cool pictures and the mathematical formulae and regard the mechanics of implementation as non-essential details, when it’s precisely those molecular details that generate the emergent property that dazzles them.

Let’s consider another classic Thompson example. Thompson was well-known for his work on how different forms could be generated by allometric transformations, and here’s one of his illustrations showing the relationship between the shape of the pelvis in Archaeopteryx and Apatornis, a Cretaceous bird. He’s making the point that one seems to be a relatively simple geometric transformation of the other, that you could describe one in terms of the changes in a coordinate grid.

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By use of simple mathematical transforms, one can generate a whole range of intermediates, fitting perfectly with the Darwinian idea of incremental change over time. Again, this is where Thompson falls short; he’s so enamored with the ideal of a mathematical order that he doesn’t consider the implementation of the algorithm in real biology.

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That mechanism of making the transformation is the crucial step. Thompson can see it as a distortion of a coordinate grid, but there is no grid in the organism. What there are are populations of cells in the developing embryo that interact with each other through molecular signals and changes in gene expression; the form is the product of an internal network of genes regulating each other, not an external ideal. Ignore the artificial grid, and imagine instead a skein of genes in a complex regulatory network, changes in one gene propagating as changes in the pattern of expression of other genes. A mutation in one gene tugs on the whole skein, changing the outcome of development in a way that is, by the nature of the whole complex, going to involve shifts in the pattern of the whole regulated structure.

There is nothing in this concept that vitiates our modern understanding of evolutionary theory, the whole program of studying changes in genes and their propagation through populations. That’s the mechanism of evolutionary change. What evo-devo does is add another dimension to the issue: how does a mutation in one gene generate a ripple of alterations in the pattern of expression of other genes? How does a change in a sequence of DNA get translated into a change in form and physiology?

Those are interesting and important questions, and of course they have consequences on evolutionary outcomes…but they don’t argue against genetics, population genetics, speciation theory, mutation, selection, drift, or the whole danged edifice of modern evolutionary biology. To argue otherwise is like claiming the prettiness of a flower is evidence against the existence of a root.

We’re all pluralists now

We’re just not all willing to admit it, and some of us tend to overemphasize our own disciplines too much. I admit that I think the most interesting, key innovations in metazoan evolution all involve shifts in gene regulation — recombinations of genes, novel interactions between genes being more important than new genes themselves. Others will argue that those are changes in genes, and that focusing on regulation is not so much a dramatic revolution as a narrowing of interest to a subset of heritable change. I will say that evolutionary history is dominated by random chance, that all those “free-riders” that Fodor and Piattelli-Palmarini sieze upon as arguments against evolution are actually the coolest aspects of evolution, and represent the bulk of the diversity and specializations that we see in the natural world. Others will argue that selection is the engine of functionality, the one process that produces useful adaptations.

We’re all arguing for the same core ideas, though, just emphasizing different aspects. Life on earth evolved. Selection is the process that produces more efficient matching of organism to the environment, chance is the process that produces greater diversity. We all study these processes through our own lenses, our own specialties, and complaining that Charles Darwin’s lens had defects is irrelevant and silly — we already knew that, just as we all know our own lenses are imperfect. That’s why we all work together and argue and argue and argue, testing our ideas, trying to work out clearer, closer approximations to the truth.

Fodor and Piattelli-Palmarini are following on a grand tradition of noticing the fact that evolution is complex and uses a multiplicity of mechanisms to play one strand of science against another; that because one discipline emphasizes selection and another emphasizes diversity and another emphasizes regulation and another emphasizes coding sequences, the differences between each mean the whole tapestry must be wrong. It’s fallacious reasoning. (I must also add that arguing that just one strand is the important one is also the wrong way to address the problem.) All it demonstrates is that they are blind to the big picture of evolutionary biology.

It’s also embarrassing to a developmental biologist that they should try to ride our field as if it were a refutation of that big picture of evolutionary biology. They can talk about constraints and gene regulatory networks and developmental mechanics all they want, but don’t be fooled: neither Fodor nor Piattelli-Palmarini are developmental biologists. Their authority is that of the bystanding dilettante, and while they mouth the words, they don’t seem to grasp the meaning.

Religion: adaptation or by-product?

For years, whenever someone asks me about the evolution of religion, I explain that there are two broad categories of explanation: that religion has conferred a selective advantage to people who possessed it, or that it was a byproduct of other cognitive processes that were advantageous. I’m a proponent of the byproduct explanation, myself; I tend to go a little further, too, and suggest that religion is a deleterious virus that is piggy-backing on some very useful elements of our minds.

Now look at this: there is a wonderful paper by Pyysläinen and Hauser, The origins of religion : evolved adaptation or by-product?, that summarizes that very same dichotomy (without my extension, however). Here’s the abstract:

Considerable debate has surrounded the question of the origins and evolution of religion. One proposal views religion as an adaptation for cooperation, whereas an alternative proposal views religion as a by-product of evolved, non-religious, cognitive functions. We critically evaluate each approach, explore the link between religion and morality in particular, and argue that recent empirical work in moral psychology provides stronger support for the by-product approach. Specifically, despite differences in religious background, individuals show no difference in the pattern of their moral judgments for unfamiliar moral scenarios. These findings suggest that religion evolved from pre-existing cognitive functions, but that it may then have been subject to selection, creating an adaptively designed system for solving the problem of cooperation.

The general argument for religion as an adaptive property is a kind of just-so story. Because humans are dependent on cooperation for survival, religion could have provided an internal bias to promote social cohesion, to promote feelings of guilt and fear about defecting from the group, and also to act as costly signals — you knew you could trust an individual to be a loyal member of your group if they were willing to invest so much effort in playing the weird religion game, just to get along. Strangers will not try to free-ride on your gang if membership involves snipping off the end of your penis, for instance. Also consider the chronic Christian condition of believing themselves to be an oppressed minority—that’s emphasized because if membership is perceived to be costly, even if it actually isn’t, it still can act as an inhibitor of free-riding.

The by-product model recognizes that there are advantages to cooperative group membership, but does not require the evolution of specifically religious properties; these are incidental features of more general cognitive capacities. In this case, we’d argue that such advantageous abilities as a theory of mind (the ability to perceive others as having thought processes like ours), empathy, and a need for social interaction are the actual products of selection, and that religion is simply a kind of spandrel that emerges from those useful abilities.

I favor the by-product theory because it is simpler — it requires fewer specific features be hardwired into the brain — and because it is readily apparent that many of us can discard all religious belief yet still function as cooperating members of a community, with no sense of loss. That suggests to me that religion is actually a superfluous hijacker of potentials we all share.

If you’re familiar with Hauser’s work, you know that he adds another datum: people moral judgments on the basis of a kind of emotional intuition. This intuition is independent of rationalizations and more complex institutional mandates, and is therefore far more deeply imbedded in our brains. We make choices based on feelings first, and the Ten Commandments are invoked later. Religion may work to reinforce some of those feelings, however, so it could act as a kind of cultural amplifier of more intrinsic biases.

To the extent that explicit religiosity cannot penetrate moral intuitions underlying the ability to cooperate, religion cannot be the ultimate source of intra-group cooperation. Cooperation is made possible by a suite of mental mechanisms that are not specific to religion. Moral judgments depend on these mechanisms and appear to operate independently of one’s religious background. However, although religion did not originally emerge as a biological adaptation, it can play a role in both facilitating and stabilizing cooperation within groups, and as such, could be the target of cultural selection. Religious groups seem to last longer than non-religious groups, for example.

In the future, more experimental research is needed to probe the actual relationship between folk moral intuitions and intuitive beliefs about afterlife, gods and ancestors. It seems that in many cultures religious concepts and beliefs have become the standard way of conceptualizing moral intuitions. Although, as we have discussed, this link is not a necessary one, many people have become so accustomed to using it, that criticism targeted at religion is experienced as a fundamental threat to our moral existence.

The idea that religion did not give us an evolutionary advantage, but has been shaped by cultural evolution to better fit and support our productive behaviors, is an interesting one. Of course, it doesn’t make religion right or good; what it suggests is that the strength of free-thinking communities could take advantage of some of the cognitive contrivances of religion, without the extraneous baggage of god-belief. We could just add a few costly signals to atheism, for instance.

So I’m going to have to ask you all to get genital piercings if you want to be a New Atheist.

(Don’t worry, just kidding!)

(via björn.brembs.blog)

Evolution: How We and All Living Things Came to Be

People keep asking me for books on evolution for their kids, and I have to keep telling them that there is a major gap in the library. We have lots of great books for adults, but most of the books for the younger set reduce evolution to stamp collecting: catalogs of dinosaurs, for instance. I just got a copy of a book that is one small step in filling that gap, titled Evolution: How We and All Living Things Came to Be(amzn/b&n/abe/pwll) by Daniel Loxton. It’s beautifully illustrated, and the organization of the book focuses on concepts (and misconceptions!) of evolution, explaining them in manageable bits of a page or two. The first half covers the basics of evolutionary theory — a little history of Darwin, the evidence for selection and speciation, short summaries of how selection works, that sort of thing. The second half covers common questions, such as how something as complex as an eye could have evolved, or where the transitional fossils are. The book is aimed at 8-13 year olds, and it’s kind of cute to see that most creationists could learn something from a book for 8 year olds.

I recommend it highly, but with one tiny reservation. The author couldn’t resist the common temptation to toss in something about religion at the end, and he gives the wrong answer: it’s the standard pablum, and he claims that “Science as a whole has nothing to say about religion.” Of course it can. We can confidently say that nearly all religions are definitely wrong, if for no other reason than that they contradict each other. We also have a multitude of religions that make claims about the world that are contradicted by the evidence. It’s only two paragraphs, and I sympathize with the sad fact that speaking the truth on this matter — that science says your religion is false — is likely to get the book excluded from school libraries everywhere, but it would have been better to leave it out than to perpetuate this silly myth.

Don’t worry about it, though — take the kids aside and explain to them that that bit of the book is wrong, which is also a good lesson to teach, that you should examine everything critically, even good pro-science books.

Say, did you know that Darwin Day is coming up soon? Maybe you should order a copy fast for the kids in your life!

Casey Luskin embarrasses himself again

Once again, the Discovery Institute stumbles all over itself to crow victory over evolution, led by the inspiring figure of that squeaking incompetent, Casey Luskin. This time, what has them declaring the bankruptcy of evolution is the discovery of tetrapod trackways in Poland dating back 395 million years. I know, it’s peculiar; every time a scientist finds something new and exciting about our evolutionary history, the bozos at the DI rush in to announce that it means the demise of Darwinism. Luskin has become the Baghdad Bob of creationism.

The grounds for this announcement is the bizarre idea that somehow, older footprints invalidate the status of Tiktaalik as a transitional form, making all the excitement about that fossil erroneous. As we’ve come to expect, though, all it really tells us is that Casey Luskin didn’t comprehend the original announcement about Tiktaalik, and still doesn’t understand what was discovered in Poland.

The fossil tetrapod footprints indicate Tiktaalik came over 10 million years after the existence of the first known true tetrapod. Tiktaalik, of course, is not a tetrapod but a fish, and these footprints make it very difficult to presently argue that Tiktaalik is a transitional link between fish and tetrapods. It’s not a “snapshot of fish evolving into land animals,” because if this transition ever took place it seems to have occurred millions of years before Tiktaalik.

Errm, no. Shubin and Daeschler are smart guys who understand what fossils tell us, and they never, ever argued that Tiktaalik‘s status as a transitional form depended on slotting it in precisely in a specific chronological time period as a ‘link’ between two stages in the evolution of a lineage. A fossil is representative of a range of individuals that existed over a window of time; a window that might be quite wide. They would never express the kind of simplistic, naive view of the relationship of a fossil that the DI clowns seem to have. For instance, here’s a picture of the relationship between various fossils, as published in Nature when Tiktaalik was announced.

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The lineage leading to modern tetrapods includes several fossil animals that form a morphological bridge between fishes and tetrapods. Five of the most completely known are the osteolepiform Eusthenopteron; the transitional forms Panderichthys and Tiktaalik; and the primitive tetrapods Acanthostega and Ichthyostega. The vertebral column of Panderichthys is poorly known and not shown. The skull roofs (left) show the loss of the gill cover (blue), reduction in size of the postparietal bones (green) and gradual reshaping of the skull. The transitional zone (red) bounded by Panderichthys and Tiktaalik can now be characterized in detail. These drawings are not to scale, but all animals are between 75 cm and 1.5 m in length. They are all Middle–Late Devonian in age, ranging from 385 million years (Panderichthys) to 365 million years (Acanthostega, Ichthyostega). The Devonian–Carboniferous boundary is dated to 359 million years ago.

Notice what you don’t see? They didn’t publish this as a direct, linear relationship that could be disrupted by a minor anachronism. It does not look like this:

Ichthyostega
↑
Acanthostega
↑
Tiktaalik
↑
Panderichthys
↑
Eusthenopteron
↑

These are all cousins branching off the main stem that led to modern tetrapods. Tiktaalik was almost certainly not our direct ancestor, but a distant cousin that was representative of a transitional state in the branching cloud of species that emerged out of the Devonian. And the authors of these papers knew that all along, weren’t shy about stating it, and if they made an error about anything, it would be in assuming that a gang of self-styled scholars who claim to be presenting a serious rebuttal to evolutionary ideas would actually already understand a basic concept in paleontology.

You would think Luskin would have also read the Niedzwiedzki paper that describes this new trackway, which rather clearly describes the implications of the discovery. It does not declare Tiktaalik to be uninteresting, irrelevant to understanding the transition between fish and tetrapods, or that Tiktaalik is no longer a transitional form. It clearly is.

No, here’s the new picture of tetrapod evolution that Niedzwiedzki and others have drawn. At the top is a diagram of the relationships as understood before the discovery, at the bottom is the new order.

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Phylogenetic implications of tracks. a, Phylogeny of selected elpistostegids and stem tetrapods fitted to Devonian stratigraphy. The grey bar indicates replacement of elpistostegids by tetrapods in body fossil record. b, Effect of adding the Zachełmie tracks to the phylogeny: the ghost ranges of tetrapods and elpistostegids are greatly extended and the ‘changeover’ is revealed to be an artefact. Pan, Panderichthys; Tik, Tiktaalik; Elp, Elpistostege; Liv, Livoniana; Elg, Elginerpeton; Ven, Ventastega; Met, Metaxygnathus; Aca, Acanthostega; Ich, Ichthyostega; Tul, Tulerpeton. ANSP 21350 is an unnamed humerus described in ref 17. The bars are approximate measures of the uncertainty of dating. These are not statistical error bars but an attempt to reflect ongoing debate.

Look closely.

Hey, the branches are the same! The relationships are unchanged! What has changed is that the branches of the tree go back deeper in time, and rather than a sharp changeover, there was a more prolonged period of history in which, clearly, fish, fishapods, and tetrapods coexisted, which isn’t surprising at all. Tetrapod evolution was spread out over a longer period of time than was previously thought, but this is simply a quantitative shift, not a qualitative change in our understanding of the relationships of these animals. It also says that there is the potential for many more fossils out there over a bigger spread of time than was expected, which is something we can look forward to in future research. Not research from the Discovery Institute, of course. Research from real scientists.

Now also, please look at the b phylogeny above, and tell me where the evidence for Intelligent Design creationism in this new figure lies. Perhaps you can see how a cladogram illustrating the evolutionary relationships between a number of fossils challenges our understanding of evolutionary history, because I don’t see it. If anything, it affirms the evolution, not the Sudden Appearance by Divine Fiat, of tetrapods.

For extra credit, explain where in diagram b of the Niedzwiedzki paper it shows that Tiktaalik has been “blown out of the water,” as Luskin puts it. Should they have scribbled in a frowny face or a skull and dagger next to the Tiktaalik bar, or perhaps have drawn a big red “X” over it? Because I can guarantee you that Niedzwiedzki and coauthors still consider Tiktaalik a transitional form that is part of the story of tetrapod evolution. All they’ve done is put it on the end of a longer branch. Nothing has changed; Tiktaalik is still a revealing fossil that shows how certain vertebrates switched from fins to limbs.

Finally, just for fun, maybe you can try to explain how the “Big Tent” of Intelligent Design creationism is going to explain how the Young Earth creationists in their camp — you know, the ones that think the planet is less than ten thousand years old — are going to find it heartening that a fossil discovery has pushed one stage in tetrapod evolution back farther by another 20 million years. That’s 2 x 103 times greater than the entire span of time they allow for the existence of the universe, all spent in shaping a fin into a foot. There ought to be some feeble expression of cognitive dissonance out of that crowd, but I suspect they won’t even notice; as Luskin shows, they aren’t particularly deep thinkers.

Ahlberg PE, Clack JA (2006) A firm step from water to land. Nature 440:747-749.

Daeschler EB, Shubin NH, Jenkins FA (2006) A Devonian tetrapod-like fish and the evolution of the tetrapod body plan. Nature 440:757-763.

Niedzwiedzki G, Szrek P, Narkiewicz K, Narkiewicz M, Ahlberg PE (2010) Tetrapod trackways from the early Middle Devonian period of Poland. Nature 463(7277): 43-48.

Shubin NH, Daeschler EB, Jenkins FA (2006) The pectoral fin of Tiktaalik roseae and the origin of the tetrapod limb. Nature 440:764-771.

Tetrapods are older than we thought!

Some stunning fossil trackways have been discovered in Poland. The remarkable thing about them is that they’re very old, about 395 million years old, and they are clearly the tracks of tetrapods. Just to put that in perspective, Tiktaalik, probably the most famous specimen illustrating an early stage of the transition to land, is younger at 375 million years, but is more primitive in having less developed, more fin-like limbs. So what we’ve got is a set of footprints that tell us the actual age of the transition by vertebrates from water to land had to be much, much earlier than was expected, by tens of millions of years.

Here are the trackways. Note that what they show is distinct footprints from both the front and hind limbs, not drag marks, and all that that implies: these creatures had jointed limbs with knees and elbows and lifted them and swung them forward to plant in the mud. They were real walkers.

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Trackways. a, Muz. PGI 1728.II.16. (Geological Museum of the Polish Geological Institute). Trackway showing manus and pes prints in diagonal stride pattern, presumed direction of travel from bottom to top. A larger print (vertical hatching) may represent a swimming animal moving from top to bottom. b, On the left is a generic Devonian tetrapod based on Ichthyostega and Acanthostega fitted to the trackway. On the right, Tiktaalik (with tail reconstructed from Panderichthys) is drawn to the same shoulder-hip length. Positions of pectoral fins show approximate maximum ‘stride length’. c, Muz. PGI 1728.II.15. Trackway showing alternating diagonal and parallel stride patterns. In a and c, photographs are on the left, interpretative drawings are on the right. Thin lines linking prints indicate stride pattern. Dotted outlines indicate indistinct margins and wavy lines show the edge of the displacement rim. Scale bars, 10 cm.

They were also big, approximately 2 meters long. What you see here is a detailed scan of one of the footprints of this beast; no fossils of the animal itself have been found, so it’s being compared to the feet of Ichthyostega and Acanthostega, two later tetrapods. There are definite similarities, with the biggest obvious difference being how much larger the newly-discovered animal is. Per Ahlberg makes an appearance in a video to talk about the size and significance of the mystery tetrapod.

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Foot morphologies. a, Laser surface scan of Muz. PGI 1728.II.1, left pes. b, Complete articulated left hind limb skeleton of Ichthyostega, MGUH f.n. 1349, with reconstructed soft tissue outline. c, Left hind limb of Acanthostega, reconstructed soft tissue outline based on skeletal reconstruction in ref. 8. We note the large size of the print compared to the limbs of Ichthyostega and Acanthostega, and that the print appears to represent not just the foot but the whole limb as far as the knee. d, digit; fe, femur; ti, tibia; fi, fibula; fib, fibulare. Scale bars, 10 mm.

What’s it all mean? Well, there’s the obvious implication that if you want to find earlier examples of the tetrapod transition, you should look in rocks that are about 400 million years old or older. However, it’s a little more complicated than that, because the mix of existing fossils tells us that there were viable, long-lasting niches for a diversity of fish, fishapods, and tetrapods that temporally coexisted for a long period of time; the evolution of these animals was not about a constant linear churn, replacing the old model with the new model every year. Comparing them to cars, it’s like there was a prolonged window of time in which horse-drawn buggies, Stanley Steamers, Model Ts, Studebakers, Ford Mustangs, and the Honda Civic were all being manufactured simultaneously and were all competitive with each other in specific markets…and that window lasted for 50 million years. Paleontologists are simply sampling bits and pieces of the model line-up and trying to sort out the relationships and timing of their origin.

The other phenomenon here is a demonstration of the spottiness of the fossil record. The Polish animal has left us no direct fossil remains; the rocks where its footprints were found formed in an ancient tide flat or lagoon, which is not a good location for the preservation of bones. This suggests that tetrapods may have first evolved in these kinds of marine environments, and only later expanded their ranges to live in the vegetated margins of rivers, where the flow of sediments is much more conducive to burial and preservation of animal remains. That complicates the story, too; not only do we have diverse stages of the tetrapod transition happily living together in time, but there may be a bit of selective fossilization going on, that only preserves some of the more derived forms living in taphonomically favorable environments.

Niedzwiedzki G, Szrek P, Narkiewicz K, Narkiewicz M, Ahlberg PE (2010) Tetrapod trackways from the early Middle Devonian period of Poland. Nature 463(7277): 43-48.

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!