Intelligent Design creationists are extremely fond of diagrams like those on the left. Textbook illustrators like them because they simplify and make the general organization of the components clear—reducing proteins to smooth ovoids removes distractions from the main points—but creationists like them for the wrong reasons. “Look at that—it’s engineered! It’s as if God uses a CAD program to design complex biological systems!” They like the implication that everything is done with laser-guided precision, and most importantly, that every piece was designed with intent, to fill a specific role in an apparatus that looks like it came out of a high-tech machine shop at a Boeing aerospace lab.
This is, of course, misleading. Real organelles in biology don’t look glossy and slick and mechanical; they look, well, organic, with fuzziness and variability and, most importantly, mistakes and slop. What these biological machines look like is not the precisely engineered output of a modern machine shop, but like bricolage. Bricolage is a term François Jacob used to contrast real biology with the false impression of nature as an engineer. It’s an art term, referring to constructions made with whatever is at hand, a pastiche of whatever is just good enough or close enough to the desired result to make do. It covers everything from the sculptures of Alexander Calder to those ticky-tacky souvenirs made from odd bits of driftwood and shells glued together that you can find at seashore gift shops.
The closer we look at the developmental biology of organisms, the more apparent the impromptu, make-do nature of their construction is. This is not to imply that they don’t work well or efficiently, but only that the signature of intent is missing. What we see is function cobbled together out of scrap from the junkyard. One clear example of this property is a gene, nanos, in Drosophila.
First, a brief review. Previously, I wrote about maternal effect genes . Some genes, the maternal effect genes, are expressed in the mother’s genome and are essential for packaging information into the egg before it is laid. The example I used was bicoid, a gene that is expressed in the mother fly’s ovaries and which produces a gene product that is stored in high concentration at the front end of the egg, and at low concentration at the back end. When the embryo is developing, cells can detect the concentration of bicoid and turn on their own, zygotic genes accordingly. The first zygotic genes in the fly are called the gap genes, and they turn on in discrete bands along the length of the embryo. For instance, one gap gene is called hunchback, and it is turned on only where the bicoid concentration is high, at the front end, and it is not turned on at all in the back half of the embryo, and there are other genes that are only active in the back half, and are turned off in the front.
The story is a little more complicated than that. There is this lovely gradient of the bicoid morphogen that is essential for specifying the front end of the animal; lose it by mutation, and the embryo can’t make a head. However, there is also a posterior gradient, a substance that is in high concentration in the back and low in front, that is essential for specifying posterior structures. That substance is called nanos, another maternal effect gene. Flies with a mutant nanos gene produce embryos that lack abdomens.
So, the fly actually has two complementary gradients, one of bicoid and another of nanos, both essential for determining the anterior-posterior organization of the animal. The fly invests a lot of effort into setting up these gradients; there is an army of genes (staufen, valois, oskar, vasa, tudor, to name a few) dedicated to making sure that the nanos gradient is set up properly, and another, smaug, that works to prevent any nanos that leaks into the wrong places from getting expressed. Obviously, nanos is mission-critical stuff that has to be in exactly the right place at the right time. What does it do?
I’ve already explained what bicoid does: it’s a transcription factor that binds to DNA and turns genes off and on. Nanos is a little bit weird. All it does, as far as we know, is bind to hunchback RNA and modify it so that it can’t be translated. That’s it. It’s an inhibitor of hunchback activity.
The reason the fly needs that is also illustrated in the diagram above. There’s bicoid high at the anterior end, and nanos high at the posterior end, and…hunchback all over the place. Remember that I told you that hunchback is a zygotic gene that is turned on in the embryo in response to bicoid? That’s true, but there’s another complication: the mother fly also packs the egg with a low level of maternal hunchback RNA. We don’t know why. It seems rather useless, and actually interferes with normal development. If nanos is not present, it is the elevated levels of hunchback at the posterior end of the embryo that confuses cells there, and makes them develop into more anterior structures. What the nanos protein does is illustrated here—it simply purges hunchback from the posterior end of the embryo.
There’s a telling experiment that reveals how trivial the function of nanos is. We can make flies in the lab that lack maternal nanos. We can make flies that lack maternal hunchback. We can make flies that lack both maternal nanos and maternal hunchback, and here’s the kicker, these flies produce embryos that develop completely normally. Maternal hunchback RNA is a mistake, a sloppy bit of unnecessary secretion that does nothing for the embryo, and maternal nanos is an elaborate, Rube-Goldberg mechanism that has been patched in to correct the stupid mistake.
Now if I were an intelligent designer building a fly from scratch, and I saw this little design defect, the way I would correct it is the obvious one: I’d fix the fly ovaries so that they weren’t dribbling a completely useless protein into the egg. I wouldn’t assemble a complex of a half-dozen proteins that were integrated into the cytoskeleton and pump a hunchback-suppressor to the right place, with other proteins floating around to make sure my hunchback-suppressor didn’t do damage in the places where hunchback is supposed to be turned on.
As design, the nanos posterior gradient simply doesn’t make sense. As bricolage, however, it’s perfectly reasonable. Evolution does not demand a best or elegant solution, only one that works well enough. We suspect that other insects have more essential gradients of posterior positional information, and that Drosophila has inherited this mechanism from ancestors that relied more on it. Flies have some oddities to their development, though, and they’ve come to depend more and more on the bicoid gradient, and the posterior gradient system has been declining in importance. Nanos localization is a module that’s been sitting in the Drosophila junkyard, and now it persists to compensate for a little slack in the mRNA packaging system of the ovaries.
Of course in 100 million years the hunchback RNA may have evolved right out of the fly’s reproductive proteins. Then the ID zealots will come back with a resounding Told You So.
David Goodsell at the Scripps Institute has a much more “realistic” molecular diagram of a flagellum in E coli here.
My understanding of the morphogen hypothesis is that transcriptional activies are being directly regulated by the concentration of molecules detected by a particular cell. It is perhaps simple to assert this when we are looking at diagrams that have only a few gradients and an expression pattern that switches at some point in the gradient. One could also imagine that cell expression fates are being regulated by a simple presence or absence (not gradient) of the “morphogen” and different cell fates are actually a matter or presence or absence of more chemical cues than we are presently aware of (not being grahped). Are there data out there that specifically refute this alternative?
TEST
Slightly tangential question : Is there any standard for regulatory circuit schematics, like one here ?
Bravo PZ, bravo. I’m about as far removed from science as you can, professionally, be (international trade) but this was both easy to understand and interesting. I realize this is about as superficial an explanation as a puddle is deep, but getting the layman to understand genes and gene expression is wonderful. Now if we could only get those pesky ID’ers to understand…
Obviously flies aren’t Intelligently Designed.
But, see how PERFECT my left pinky is; it just has to be proof of a higher power.
Flies were front-loaded at the cambrian explosion to become the servants of Baal-zebub; and to use their developmental biology to drive men astray from the one true path.
There`s just one problem with it all: LASER PRECISION wouldn`t be nearly enough, rather photonic precision (or hey why not call it molecular precision and the science behind it molecular biology) is what it is all about (e.g. retinol). Or one could just deduce that the lack of eduction of those creationists as well as psychological aspects of group dynamics is the problem in the first place.
John Wilkins wrote:
That is really neat – particularly since they are for public use! It looks almost like pointillism. It is easy enough to generate text for websites, more or less, but difficult to get ahold of good images, and without the images, a website will look fairly sparse.
David Goodsell was interviewed about his cellular and molecular illustrations by American Scientist last year. Goodsell wrote in Am Sci 2000 about “Biomolecules and Nanotechnology”
Heather wrote:
If I remember correctly, early analyses were based upon a form of boolean analysis which assumed that genes were either being transcribed or not. Calculations based upon differential equations, for example, have proven more difficult, but a boolean-type analysis was simply failing to properly describe the phenomena.
No doubt there will be plenty of cases where we will assume that only so many transcription factors are involved, at least temporarily, but a return to some sort of widespread boolean analysis per se now seems highly unlikely. We are getting better at identifying transcription factors and enhancers and how they determine the degree to which a given protein is expressed.
No doubt there is still a great deal of complexity involved, particularly as the result of the complexity of protein structure and interaction. However, we are likewise developing models which may be used to explain and largely identify protein structure simply on the basis of coding sequence. Moreover, now that we have “finished” the genome project, groups are moving ahead with the mapping of the transcriptome (RNA) and the proteonome (the genome-wide protein and protein interaction network).
It helps to keep in mind that the number of coding genes is fairly limited, roughly 25,000. However, given alternate splicing, the number of proteins which these code for is closer to 75,000 — so there are going to be limits to the sort of complexity that would be possible simply in terms of a boolean approach. Likewise, if I remember correctly, the good majority of proteins which are used as transcription factors are regulatory proteins rather than structural proteins, and they number less than 200 in humans. So once again, this reduces the potential for that sort of complexity.
However, one point which is important beyond simply the transcription factors is the extent to which cells are already commited to a given line of development. This appears to be largely the result of histone markers, one of which indicates that a given part of the code should never be transcribed whereas the other indicates that it should be transcribed. Sections of code will begin with both markers in a state of bivalence, then, during development, one marker or the other will be lost.
Incidentally, we are also getting to the point at which we should be able to develop detailed phylogenetic trees beginning with the omnipotent stem cell, with each potential final state being represented as a node in the tree. This may be done by tracking the ancestry of cells by means of shared mutations, much the same way that we are currently doing in terms of evolution now.
I could look up some of the relevant articles if anyone is interested in one point or another.
Bricolage may be an art term, but Francois Jacob probably didn’t mean it that way. It’s the ordinary French term for do-it-yourself home improvements, with all the amusing connotations of inept workmanship and amateur results that do-it-yourself has in the US. Forget art styles and think about hanging a picture crooked, with a whopping hole in the plaster, and you’ve got it about right.