Pharyngula

Segmentation genes evolved undesigned

Jason Rosenhouse has dug into the details of the evo-devo chapter of Behe’s The Edge of Evolution and found some clear examples of dishonest quote-mining (so what else is new, you may be thinking—it’s what creationists do). I’ve warned you all before that when you see an ellipsis in a creationist quote, you ought to just assume that there’s been something cut out that completely contradicts the point the creationist is making; Rosenhouse finds that Behe gets around that little red-flag problem by simply leaving out the ellipses.

I just want to expand a little bit on one point Behe mangles and that Jason quotes. It turns out I actually give a lecture in my developmental biology courses on this very issue, the mathematical modeling antecedents to insect segmentation, so it’s simply weird to see Behe twisting a subject around that is so well understood in the evo-devo community, and that was actually well explained in Sean Carroll’s Endless Forms Most Beautiful.

First, here is what Behe says. There is a germ of truth to these particular quotes, but the conclusions and the details are all wrong.

The next unwitting evo-devo point is even more striking: Basic features of life were totally unpredicted by Darwin’s theory. In fact, reasoning straightforwardly in terms of Darwin’s theory led badly astray even the most eminent evolutionary biologists, who reached conclusions completely opposite to biological reality..

As you’ll see, there were unexpected details of developmental patterning that were not predicted; that part is true, and unsurprising. If there’s one thing we know about evolution, it is that outcomes are influenced by chance, which means we can’t very well sit down ahead of time and lay out the entire future of a lineage, anymore than we can sit down to a poker game and predict how every hand will be played.

But there are other problems with Behe’s claim. What he’s about to explain are not “basic features of life”, but the specifics of metazoan pattern formation. We know already that there are multiple ways you can generate patterns in an organism; the “mistake” we saw made was that developmental biologists sensibly proposed the simplest explanation first, as wise old Ockham would have instructed us, and discarded that as more complications were discovered.

Another error by Behe: these were not ideas derived from “Darwin’s theory”. Darwin’s theory was a general description of how organisms evolved. He did not know anything about genes, morphogens, reaction-diffusion models, computers, or any of the concepts used in this kind of work.

And finally, the early conclusions were not opposite biological reality. The early modeling is still useful and can be used to explain what’s going on in, for instance, vertebrates; it simply turned out that the animal model used in early investigations of the molecular basis of pattern formation, Drosophila, is highly derived and has acquired some very specific, hard-coded regulatory elements on top of a general principle.

Behe is all worked up about one particular example of pattern formation, segmentation. Many metazoans are built around repeating structures—for example, our vertebrae, the stripy organization of annelids, and the obvious cuticular segmentation of arthropods—and prior to the molecular genetics revolution in developmental biology that began in the 1980s, researchers sought out minimal models to explain how you could generate a pattern of repeating elements in an animal. This was some clever and elegant work, but Behe simply and incorrectly dismisses it as entirely wrong by quoting Sean Carroll out of context, and as if the results somehow invalidate evolutionary biology.

Mathematicians, too, were fooled, “Many theoreticians sought to explain how periodic patterns [such as fruit fly embryo segments] could be organized across large structures. While the maths and models are beautiful, none of this theory has been borne out by the discoveries of the last twenty years.” “The continuing mistake is being seduced into believing that simple rules that can generate patterns on a computer screen are the rules that generate patterns in biology.”

I’m fairly familiar with the older literature on pattern formation—I had the good fortune to have gotten my undergraduate training in developmental biology under the old paradigm, and gone on to grad school as the evo-devo influence was just beginning to grow. Mathematicians weren’t “fooled”. They were trying to model how, for instance, a chemical gradient could be transformed into a reiterating pattern of specific activation of other chemicals. It was good stuff; read some of Hans Meinhardt’s modeling work, for instance, which was very useful in explaining patterns of gene activation, once the genes had been identified. It was also not just free-floating speculation with a computer—Klaus Sander, as one example, was an excellent experimentalist who postulated the existence of gradients of morphogens from perturbations of embryos before the specific molecular agents were identified.

It was all interesting work, but as Jason points out and as Carroll clearly states, it wasn’t derived from Darwinian principles. It was from a very clever computer scientist and mathematician.

The revelation of how these stripe-making switches work clarified a long-standing question in the study of pattern formation in biological structures. For several decades, mathematicians and computer scientists were drawn to the periodic patterns of body segmentation, zebra stripes, and seashell markings. Heavily influenced by a 1952 paper by the genius Alan Turing (a founder of computer science who helped crack the German Engima code in World War II), “The Chemical Basis of Morphogenesis,” many theoreticians sought to explain how periodic patterns could be organized across entire large structures. While the math and models are beautiful, none of this theory has been borne out by the discoveries of the last twenty years. The mathematicians never envisioned that modular genetic switches held the key to pattern formation, or that the periodic patterns we see are actually the composite of numerous individual elements.

There is some beautiful work on reaction-diffusion models and chemical oscillators that generate nice striped patterns on computer screens and in petri dishes. It was very seductive, and you can’t blame the early investigators for thinking that maybe this was the answer to how embryos assigned cells to segments. It was nice math, and it was all so very elegant and simple. All you needed was a source and a sink for a couple of diffusible reactants with some specific properties, and voila, repeating stripes emerge.

However, the work on Drosophila segmentation (and Carroll was a prominent contributor to that) showed a different, more complex pattern, that instead of a few components that oscillated in their expression along the body axis, there were many components, and that each one had complex regulatory elements that responded in a discrete fashion to a gradient of a morphogen and to specific epistatic interactions with many other genes.

Neither result, either a simple system with few components or a complex system with many genes intricately regulated, contradicts evolutionary theory. For Behe to imply that modern evo-devo in any way justifies doubt about evolution is dishonest—the regulatory elements that Carroll is describing evolved. There’s a reason I reposted that article on pair-rule genes yesterday — these are the genes Carroll and Behe are discussing. Behe looks at that complicated hodge-podge of madly interacting genes, and thinks it must be designed; Carroll and I look at it and see bricolage, semi-random elements recruited ad hoc and incrementally into a functional assemblage.

What Carroll is talking about when he says that patterns are a “composite of numerous individual elements” rather than the elegant, simple mathematical rules of the early developmental modelers is this: when we look in Drosophila at a gene like even-skipped that has a beautifully periodic expression pattern — it’s turned on in segments 1, 3, 5, 7, etc. — we don’t find a general rule that controls gene expression in a clever way, we find brute force clumsiness. I know there are some people who’ve done some computer programming reading this. Imagine you’ve got some simple problem you’re supposed to solve, where when a certain variable is odd, you do X, and if it’s even, you do Y. You’d probably code something like this:

if ((segment_number mod 2)==1) then
    X
else
    Y;

You’d try to devise some simple function that varies with the desired pattern, and use that to control conditional expressions. That is not how the fruit fly does it. The fruit fly does it in the way the idiot freshman in intro computer science would do it.

if segment_number==1 then
    X;
if segment_number==2 then
    Y;
if segment_number==3 then
    X;
if segment_number==4 then
    Y;
if segment_number==5 then
    X;

Expression in each segment is hard-coded in the regulatory elements of the gene. Yikes. There is nothing clean and simple here. And it gets even worse: the fly has nothing equivalent to a simple “segment_number” variable. What it has is a collection of other genes with variable levels of expression, and the conditional test is to read the state of those other genes in the cell and make regulatory decisions. Here, for instance is one even-skipped stripe, in parasegment 3, with it’s level of expression (the y axis) plotted on position along the anterior-posterior axis by parasegment number. You can see where the boundaries of its expression come from — it’s activated by the hunchback and bicoid gene products, but it’s repressed by giant and Krüppel. We could probably code this as:

if bicoid && hunchback && (not giant) && (not Krüppel) then
    even_skipped;
i-9f747eab726bf241a368ed472fcbbc98-eve2.jpg

Clumsy as that is, it gets clumsier. Even-skipped also has to be active in parasegments 1 and 5 and 7 and so forth, and so we’re going to have a whole swarm of sorta-Boolean conditionals encoded in the regulatory region of even-skipped. It’s a major patchwork kludge, where tiny, easy modifiers have been swapped in by random processes over evolutionary time, each one nudging the pattern of expression closer or more robustly towards the regular pattern. This isn’t designed at all. This is what we expect from a process of random change refined by selection, and it isn’t what you get from planning.

I do have to disagree with Carroll on one thing, though. He claims that “none of [the earlier modeling work] has been borne out by the discoveries of the last twenty years.” It’s literally accurate, but a bit unfair in spirit. While the specific predictions flopped, I don’t think that’s to their discredit at all — they devised testable models and made predictions about the presence of morphogens, for instance — and their general principles are useful. I think Meinhardt, for instance, has made useful theoretical contributions to understanding how gradients contribute to morphogenesis, and his work was readily adaptable to the experimental results and the details of the molecular engines behind segmentation. Most importantly, though, don’t get trapped in Drosophila thinking. Drosophila is highly derived and intensely weird, and all those kludgy little hard-coded patches have been added over millions of years on top of what seems to be a much simpler, more primitive system … and that system seems to use a simpler network of molecular oscillators to set up periodic patterns. That simpler system seems to be what we vertebrates use. It’s nothing like what anyone predicted before, that’s true, but it is an elegant clock-and-wavefront pattern that works well.

I’m going to be very cruel and stop there. Generating periodic patterns is the subject of my next column for Seed, so you’ll have to wait for the next issue to come out. I did say a few words about the vertebrate mechanism before, though, so you can at least get a hint.


Meinhardt H (1977) A model of pattern formation in insect embryogenesis. J Cell Sci 23(1):177.

Meinhardt, H (1988). Models for maternally supplied positional information and the activation of segmentation genes in Drosophila embryogenesis. Development 104 (Suppl.), 95-110.

Sander, K (1988). Studies in insect segmentation: from teratology to phylogenetics. Development 104 (Suppl.), 111-121.

Comments

  1. #1 MikeM
    June 24, 2007

    This is what I’ve been saying about these guys, especially Behe, for a long time: They know the creationist stuff they spew is 100% false, and yet they do it anyway.

    I think it’s a form of mental illness. Delusions of grandeur, or something.

    They’ll go to the Grand Canyon, Death Valley and Zion, as I have with my family the last 3 years, and KNOW it couldn’t have been formed in any YEC model, and figure out a way to explain it in those terms anyway.

    Seriously, the stuff they think is so far removed from the stuff they insist they think that mental illness is the only possible explanation.

    Strangely, I feel no sympathy towards Behe or others similarly afflicted.

  2. #2 Blake Stacey, OM
    June 24, 2007

    My list keeps growing new segments.

    I like the analogy to computer code (and bonus points for using == to represent “equals”).

  3. #3 Dan
    June 24, 2007

    If there’s one thing we know about evolution, it is that outcomes are influenced by chance, which means we can’t very well sit down ahead of time and lay out the entire future of a lineage, anymore than we can sit down to a poker game and predict how every hand will be played.

    Clearly, you’ve never heard of the Theory of Intelligent Gambling. The winners aren’t the best gamblers, they’re the ones Jesus likes the best.

    If you doubt this is possible, how is it there are PAIRS + FLUSHES??!??!?

  4. #4 LisaS
    June 24, 2007

    Thanks for the great post! I appreciate you explaining these issues. You make it all so very fascinating. If I were starting over in college, I would consider becoming a biology major.

  5. #5 N.Wells
    June 24, 2007

    Thanks, that was remarkably clear and helpful.

    The programming analogy speaks wonders about the ‘designing process’ and the nature of the ‘designer’. The if-A, if-B, if-C, if-D approach happens in programming when an algorithm grows beyond the competence of its designer. You see it in beginning programmers who’ve learned if-then statements but who haven’t yet mastered more elegant (more recursive and self-referential) options, or somewhat better programmers who are deep into the process of adding complexities and capabilities and patches to a once-elegant routine designed for simpler tasks, because they haven’t yet been able to come up with a new and wholly different elegant solution that allows them to chuck out the old version and start over with something better. MS-DOS 8.11, as opposed to Windows 1.0 as it were.

    In hindsight, this is by far the most likely sort of system that evolutionary processes should produce: a bricolaged, satisficing, but far from perfect system. (I’ve entangled myself in impenetrable spaghetti code of my own creation often enough to know that sometimes you end up making nearly random changes, stumble into something that works, and move on. Not pretty, nor anything to be proud of, but faute de mieux. Needless to say, I’m not a professional programmer.)

    Once in a while a change may allow an old system to be chucked out in favor of the new (like the mammalian jaw joint taking over from the reptilian jaw joint), but no sooner does that happen than new changes start to kludge up the new system, producing a new round of bricolaged complexities (the three bones in the inner ear, limitation to two generations of teeth, and so on.)

    Hence if the results come from a designing deity, we clearly see a barely competent and out-of-his-depth divinity, who is about as good at bioengineering as I am at programming, or worse. Otherwise, we see about what we should expect from evolution.

  6. #6 RBH
    June 24, 2007

    It was very seductive, and you can’t blame the early investigators for thinking that maybe this was the answer to how embryos assigned cells to segments. It was nice math, and it was all so very elegant and simple. All you needed was a source and a sink for a couple of diffusible reactants with some specific properties, and voila, repeating stripes emerge.

    It’s still seductive for physicists who dabble in the area. I attended a couple of presentations given by candidates for a faculty position in physics last year who are still building reaction/diffusion models, speculating about how they might model biological phenomena, and showed us lovely animations of patterns like those at Texture Garden.

  7. #7 Monado
    June 24, 2007

    So, we’re back to Behe asking himself, “What would Jesus lie about”?

    I don’t think it’s a mental illness in the classic sense. The really mentally ill are not aware that their perceptions & conclusions are at right angles to reality. I think it’s just the result of brain pollution: nonsense poured into the head of a small child. Without the ability to evaluate what it’s told, a small child takes it as true and incorporates it into the worldview. Then it’s more comfortable to contort and rationalize reality than to change prejudices.

    We need an evolution song that’s taught to 3-year-olds, with a catchy tune like that of Sharon, Lois, & Bram’s “One elepant, deux elephants.”

  8. #8 sailor
    June 24, 2007

    “I’m going to be very cruel and stop there.”
    Not at all! After reading that post and the linked one, I feel I need a break – maybe a creationsist-bashing one.

  9. #9 Jeff R
    June 24, 2007

    More thanks for putting the problem in programming terms. And I noticed the “==” for “equals”, too. Huzzah!

    Very clear, understandable example of awkward logic, exactly what we’d expect to see in a system that was evolved, rather than designed.

  10. #10 Duff
    June 24, 2007

    MikeM,
    Its not mental illness that afflicts these guys, its fame and fortune in their weird little community. They write so the sheep and the simple people can pay the bucks for it.

  11. #11 Jason Rosenhouse
    June 24, 2007

    If only The New Republic had asked you, instead of Jerry Coyne, to review EoE for them! That was a terrific post. Thanks for filling in those details.

  12. #12 Jeff Fecke
    June 24, 2007

    Wait — sometimes scientists advance ideas that later turn out to be wrong, and then they admit they were wrong, and look for better explanations? I thought scientists claimed to be infallible!

    Oh, wait, that’s the Pope. Sorry.

  13. #13 K. Signal Eingang
    June 24, 2007

    What strikes me about an argument like Behe’s is how wholly unsatisfactory it is to anyone with a reasonable expectation of how science works. Of course the early theorists are going to get things wrong, it is only to be expected that complications will arise over the course of investigation that weren’t apparent at first. Anybody who’s worked on a moderately complicated household plumbing job can sympathize — you start out with what you think is a pretty solid idea of what you need to do, but there’s always one extra tool to buy, valve to replace, or joint to solder that you won’t find out about until you’re already elbow-deep in the project. You don’t know what you don’t know until you find out you didn’t know it. Behe, however, would have us believe that the fact you’re making one more trip to the hardware store invalidates EVERYTHING YOU KNOW about water flowing through pipes.

    The only people who could possibly be swayed by Behe’s argument are people with some confused view of scientists as pointy-hatted wizards, conjuring truth out of some ethereal realm. There’s a framing problem for you.

  14. #14 Hal
    June 24, 2007

    Not only is the segmentation pattern a product of patched-together, discrete, genetic programming units– a form that contradicts design by being inept (if the design is intelligent) and nonoptimal (if it isn’t)– but the kludgy patchiness is admirably adapted to promote further evolution as well as to refine the results of evolutionary experimentation because of the high number of potential mutation points, each of which possesses a high number of somatic effects. If it’s design, even the design of the design is pathetic.

  15. #15 Scott Hatfield, OM
    June 24, 2007

    Speaking of segments, the segment containing the oversize ‘J’ that doubtless began your post seems to be missing on my screen. Another graphics glitch?

  16. #16 Jud
    June 24, 2007

    All things Drosophila and human, the same incompetent programmer designed them all:

    “[O]ne can still understand gene transcription in terms of parallel threads of execution, with the caveat that these threads do not follow canonical, modular subroutine structure. Rather, threads of execution are intertwined in a rather ‘higgledy-piggledy’ fashion, very much like what would be described as a sloppy, unstructured computer program code with lots of GOTO statements zipping in and out of loops and other constructs.”

    http://www.genome.org/cgi/content/full/17/6/669

  17. #17 khan
    June 24, 2007

    I’m old enough to have encountered ‘spaghetti code’:GOTOs, ALTERs,…

    Not for the faint of heart.

  18. #18 Chinchillazilla
    June 25, 2007

    Clearly, you’ve never heard of the Theory of Intelligent Gambling. The winners aren’t the best gamblers, they’re the ones Jesus likes the best.

    If you doubt this is possible, how is it there are PAIRS + FLUSHES??!??!?

    Best comment ever.

    I want to print this entry out and glue it to every copy of Behe’s book I can find.

  19. #19 Brian X
    June 25, 2007

    ALTER isn’t spaghetti code… it’s something worse that there isn’t a name for.

    BTW, people actually have used that in production code? Oh dear…

  20. #20 archgoon
    June 25, 2007

    The fruit fly does it in the way the idiot freshman in intro computer science would do it.

    PZ. you are my hero. :)3

  21. #21 John Phillips
    June 25, 2007

    Personally, I think the deal with people like Behe is that they know that they are not good enough to get the fame and adulation they crave in the world of real science so instead choose to become big fishes in very small ponds and IDiotism gave them the opportunity to achieve it. The rest is simply propping it up with more and more garbage as they don’t care about the opinions of real scientists, as could be seen from his admission during the Dover trial of not having even been bothered to read the results of real scientists, especially as they contradicted him in every detail. But as long as they keep their core ‘congregation’ happy they will continue to be big fishes in very small ponds and keep the fame they require and they will continue to be trotted out by the media and the IDiots any time they need some controversy, headlines or need to claim that ‘real’ scientists support IDiotism. The fact that it isn’t respect from other scientists is neither here nor there to them as long as they get some fame to wallow in. It is much like the fame those who take part in reality shows achieve, i.e famous for being famous rather than for having achieved something of value. The difference of course, is, that unlike the airheads who take part in reality shows, Behe and his ilk try to do real damage to science education and the understanding of science generally as the price for their fame, or rather infamy.

  22. #22 Petter Hesselberg
    June 25, 2007

    Please don’t denigrate spaghetti code. If you do, a certain Flying Monster will *** arrghh *** — ploink —

  23. #23 khan
    June 25, 2007

    ALTER isn’t spaghetti code… it’s something worse that there isn’t a name for.

    BTW, people actually have used that in production code? Oh dear…

    I encountered ALTER in a legacy COBOL program in 1982. I had not been told about it in computer class nor was it in the manual. I had to ask one of the older programmers what it was.

  24. #24 Animesh Sharma
    June 25, 2007

    Excellent post! I feel if I was taught biology in this fashion, I would have learned it at a much higher pace.
    Certain things were not very clear, for example when one talks of gene variable, is repression being taken as a negative integer? Further when you say “it’s activated by the hunchback and bicoid gene products, but it’s repressed by giant and Krüppel” does it mean the expression is boolean or there is some threshold which makes it behave like boolean. Again how is repression being represented?

  25. #25 PZ Myers
    June 25, 2007

    Don’t push the analogy too far! What they’re measuring is the concentration of transcription factors, as measured by binding to regulatory sites that promote transcription of other genes. In some cases there are going to be competitive interactions between these gene products; in others there are patterns of activation by phosphorylation cascades; in others there are localization events that need to occur to move a factor into the nucleus. The boolean logic of regulation is far, far fuzzier than anything you’ll get in computer science.

  26. #26 Leon
    June 25, 2007

    Mathematicians weren’t “fooled”. They were trying to model how….

    That’s another good illustration of how these people’s thinking is sadly different from ours. For a creationist the truth is revealed, not discovered. Their line of thinking is that if they can show any scientific documents have been clearly wrong, we’ll suddenly discover the entire edifice of science is WRONG! Why didn’t we see it before? We were so foolish to not see the Bible was was the source of truth!

    Of course, those of us who prefer observation to speculation don’t see things that way. If part of one of our constructs is inaccurate, we look to see how we can correct it, or we find something more accurate to replace it.

  27. #27 Keith Douglas
    June 26, 2007

    I was pleased to see Turing mentioned in this context, even if his explorations were rudimentary by our standards today …

  28. #28 Mircea
    April 18, 2008

    Just looking at the “code” example: you forgot to put there the loop in the “better” example. And for your information, a compiler might choose to do “in lining” of a short loop if it’s feasible for speed reasons. So if you were writing your code in a high level language it will look the way you correctly say is more intelligent but if you would disassemble the generated code you might be surprised.
    Just my 2 cents…

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