The other side has it so easy.

One cause of the ongoing struggle with the Forces of Ignorance, whether they be the creationists I wrestle with or the simplistic "blow 'em up and convert 'em to Christianity" faction of the extremist right, is that simple-minded ideas can be easily expressed in soundbites and catchphrases. Jingo is always easier than nuance and depth, and has the advantage that it can appeal to people who actually don't know anything about the subject being discussed. The real world, though, is complicated. When your goal is to respond appropriately and accurately to reality, sometimes you can't just reduce it to a slogan—you have to try and educate. And often that means you have to get wordy…so I'm afraid this is going to be a longish post. I'm also targeting it at those people who aren't familiar with the basics of molecular biology, so I'm hoping it will be comprehensible to even those who haven't had a lick of college biology.

There are a couple of ideas that have been floating around among the Intelligent Design crowd that are very popular with people who don't know much biology, and the reason they appeal is because they rely on ignorance and common misconceptions, and a faulty mapping of biological properties onto other objects in our experience. Two that I hear often are the analogy of gene products as machines, to highlight their awesome sophistication, and the declaration that because they are so complex, genes can't change and evolve.

Genes as machines

This is a favorite among creationists. For example, here's a spectacularly egregious example from Michael Behe:

I mean, literally, there are real machines inside everybody’s cells and this is what they are called by all biologists who work in the field, molecular machines. They’re little trucks and busses that run around the cell that takes supplies from one end of the cell to the other. They’re little traffic signals to regulate the flow. They’re sign posts to tell them when they get to the right destination. They’re little outboard motors that allow some cells to swim. If you look at the parts of these, they’re remarkably like the machineries that we use in our everyday world.

That's impressive rhetoric—it gives several strong impressions critical to the creationist worldview. One is of purpose. Every 'machine' he mentions has a specific function and is carrying out a job. Another impression is of overwhelming complexity. Outboard motors are artifacts of human design, and we can't imagine mere chemistry building an Evinrude in a vat…therefore, we should similarly think it impossible that mere chemistry drives the activity in a cell.

Unfortunately for Behe's goals, both of those impressions are completely false.

If you actually look at these "machines", they don't resemble anything at all from our macroscopic world. Well, except maybe these: pop beads.

Remember those? Maybe you played with them as a kid, or have kids who have tinkered with them. They're just little beads of various shapes and colors with a knob on one side and a socket on the other, and you can string them together by popping the knob on one into the socket on another. Look closely at those things Behe is calling "trucks" and "busses" and "traffic signals", and what you find are pop bead necklaces, or proteins.

There are differences, of course. Cells use 20 different kinds of "beads" called amino acids. Each amino acid has different chemical properties: some are bulky and some are small, some are hydrophilic (or water-loving) and other are hydrophobic (or oily), some have acidic and some have basic side chains. The different properties cause the chain to contort and fold in characteristic ways, so you end up with a pop bead necklace that is twisted on itself to form a lump with a specific shape. The shape is important; some may take on a shape that complements another protein, so they tend to stick together. Others may form a pocket into which other chemicals in the cell might fit, and when they fall into the pocket, they are wrapped in those bulky/small/oily/wet/acidic/basic amino acids, which then promote chemical reactions.

Individual proteins do link up to form more elaborate complexes, but still…it's all a function of concentration and reaction rates and binding energies. It's chemistry. It's driven by thermodynamics and equilibria, not guided engineering.

Hmmm. Behe's metaphor isn't a very good one. He wants to pretend something is a "truck", but when we actually look closely at it, it's a knotty string, a tangle of chemicals. And it isn't driving purposefully around the cell, it's bumping around haphazardly, interacting with other components of the cell chemically. It's also nowhere near as complex as a truck, since the instructions for building one can be reduced to the order you string together a set of pop beads. Using a metaphor can be a useful strategy for getting a point across, but when the metaphor is used to carry a false message, such as the presence of purpose and detailed complexity that is not present, it is actually misleading. When you get right down to it, what's going on inside a cell is about as mindless as soup.

That's all the genetic output of a cell is, is chains of amino acids which interact chemically. Go ahead, rummage about in this useful database, Online Mendelian Inheritance in Man (it's a kind of Google for the human genome, you can search for all kinds of interesting bric-a-brac that have been found in our genetics) and you won't find trucks or busses or even traffic signs…just proteins.

For example, here's an interesting one, ASPM (that's short for Abnormal Spindle-like, Microcephaly associated). It's a chain of 1142 amino acids, which can be summarized thusly by using a different letter of the alphabet for each of the 20 possible amino acids:

    1 mslraytarc rlnrlrraac rlftsekmvk aikkleieie arrlivrkdr hlwkdvgerq
   61 kvlnwllsyn plwlriglet tygelisled nsdvtglamf ilnrllwnpd iaaeyrhptv
  121 phlyrdghee alskftlkkl lllvcfldya kisrlidhdp clfckdaefk askeillafs
  181 rdflsgegdl srhlgllglp vnhvqtpfde fdfavtnlav dlqcgvrlvr tmelltqnwd
  241 lskklripai srlqkmhnvd ivlqvlksrg ielsdehgnt ilskdivdrh rektlrllwk
  301 iafafqvdis lnldqlkeei aflkhtksik ktisllschf ddlinkkkgk rdsgsfeqys
  361 enikllmdwv navcafynkk venftvsfsd grvlcylihh yhpcyvpfda icqrttqtve
  421 ctqtgsvvln sssesddssl dmslkafdhe ntselykell enekknfhlv rsavrdlggi
  481 paminhsdms ntipdekvvi tylsflcarl ldlrkeiraa rliqttwrky klktdlkrhq
  541 erekaariiq lavinflakq rlrkrvnaal viqkywrrvl aqrkllmlkk eklekvqnka
  601 asliqamwrr yrakkylckv kaackiqawy rcwrahkeyl ailkavkiiq gcfytklert
  661 rflnvrasai iiqrkwrail pakiahehfl mikrhraacl iqahyrgykg rqvflrqksa
  721 aliiqkyira reagkherik yiefkkstvi lqalvrgwlv rkrfleqrak irllhftaaa
  781 yyhlnavriq rayklylavk nankqvnsvi ciqrwfrarl qekrfiqkyh sikkiehegq
  841 eclsqrnraa sviqkavrhf llrkkqekft sgiikiqalw rgyswrkknd ctkikairls
  901 lqvvnreire enklykrtal alhylltykh lsailealkh levvtrlspl ccenmaqsga
  961 iskifvlirs cnrsipcmev iryavqvlln vskyekttsa vydvencidi llellqiyre
 1021 kpgnkvadkg gsiftktccl laillkttnr asdvrsrskv vdriyslykl tahkhkmnte
 1081 rilykqkkns sisipfipet pvrtrivsrl kpdwvlrrdn meeitnplqa iqmvmdtlgi
 1141 py

ASPM is a very cool and important gene—some mutations in it cause microcephaly—but again, Behe's metaphor fails us. ASPM isn't a truck or a traffic signal, but does something obscure and biochemical; it's a regulator of microtubule organization. It sticks to other proteins that form the skeleton of the cell, and changes how they interact in ways that aren't completely worked out, but it somehow changes rates and periods of cell division. We human beings have a personal stake in ASPM: by regulating cell growth, it's one of the genes responsible for our big brains, it shows signs of selection for changes in our evolutionary history, and we have comparative data on its sequence in other organisms. Follow those links to find out what ASPM does, but I'm going to focus on it more as a representative protein to illustrate another fallacy, that these "machines" don't change in evolution, and that there is no evidence of the acquisition of new adaptive features in our proteins.

Genes can't change

Another common claim by creationists relies on that misconception about the complexity and purpose of gene products to argue that evolution is impossible, because change is impossible. After all, you can't go poking around making random changes in the engine of a truck and expect it to run, right? In the worst cases, this logical error can turn into outright denial of the evidence, as when creationists claim "In fact, there is no evidence for the existence of beneficial mutations in complex organisms," when in fact, there is documented evidence of beneficial mutations in modern humans.

As I've already explained, though, gene products aren't trucks, they're chains of pop beads. Of course you can change one or two or a dozen beads in a long series without totally destroying the protein; you can even make random chains of amino acids that will have function¹. It's true that some changes disrupt a specific function—if a particular acidic amino acid has to be in a particular spot in a fold of the protein to promote a reaction, deleting it can cause the protein to fail in its job. But many of the amino acids can be jiggered around and cause no change in the protein, or cause subtle changes, among which may be possible improvements in function.

Here, for instance, is a diagram of the gene sequence for ASPM. It's tiny, but if you click on it you'll get a larger and more readable version. This is the layout of the nucleotide sequence, the instructions in the DNA that specify the order of the amino acid pop beads in the final protein.

Nucleotide polymorphisms and substitutions in the human ASPM gene. The exons are shown by solid boxes and introns by lines. The sizes of exons, but not introns, are drawn to scale. The thick horizontal line above exon 18 shows the 867-nucleotide fragment that is not found in the mouse Aspm, with the two thin lines above it showing the two segments amplified in various mammals. Fixed nucleotide substitutions in the human lineage after the human-chimpanzee split are shown by circles, whereas common and rare polymorphisms within humans are shown by squares and triangles, respectively. Nonsynonymous changes are solid symbols and synonymous changes are open symbols.

The first thing to explain is that this is a linear diagram of a sequence that will be translated into a string of amino acids, which will then fold according to the properties of those building blocks into a 3-dimensional structure with chemical activity. There's also a quirk of us organisms with cells that have nuclei: our genes are broken up into stretches called exons (the darker bars in the diagram) that contain the actual instructions for the gene product, and other regions called introns (the thin lines connecting the bars) which are essentially junk that will be cut out and thrown away, and the exons spliced together. The ASPM gene is made of 28 exons.

Let's look at a closeup of the left side of the diagram to see the really interesting stuff going on in these data.

The study this was taken from examined the ASPM sequence in 14 different people from a range of backgrounds. One of the things they identified was a set of polymorphisms—"multiple forms", or ASPM genes that are different in different people—and the little triangles and squares mark where the pieces of DNA are different. In 14 people, they identified 33 common and rare polymorphisms! Obviously, this gene is tolerant of all kinds of substitutions and tinkering, which is not at all unusual. Also, most of these changes don't have any detectable effects on the individuals carrying the polymorphisms.

Another interesting observation: look at the little circles marking positions on the gene labeled "substitutions". This paper also examined other primates, and the circles mark positions in the gene that are consistently different between humans and chimpanzees. There are 22 places in the gene where all humans and all chimpanzees differ from one another. At least some of these are partially responsible for the difference in brain size between chimpanzees and humans.

Analysis of the details of these changes, such as the frequency of changes to the DNA sequence that do not cause changes in the amino acid sequence vs. those that do, comparison of rates of change with other genes, and comparisons with other species tell us quite a bit about the history of the ASPM gene: it has been subject to relatively intense selection for modifications in our history, and is currently subject to stabilizing selection to maintain its function. Genes are not static things at all, and even now we can measure variation within ourselves in this rather important, umm, "machine".

Even if one believes in Intelligent Design creationism, the mythical Designer is postulated to work by tinkering with these gene sequences; to argue that there can't be beneficial changes is to deny the Designer any capacity for Design. At the same time, though, the same random variation that produces the polymorphisms in the human population was the source for the substitutions that differentiate us from chimpanzees. There is no qualitative difference between the chemical nature of those changes—they're all a matter of swapping out different pop beads.

This is the perspective modern biology has given us, that has made the principles of evolutionary biology stronger and more cogent. We can look at our fellow species on this planet and see that ultimately, the differences between us are a consequence of the accumulation of truly minute changes, tiny switches in a simple encoded sequence. There were no radical transformations that required the privilege of godlike powers to transform an earlier ape into a man—just time and chemistry.

¹Keefe AD, Szostak JW (2001) Functional proteins from a random-sequence library. Nature 410:715-718.

²Zhang J (2003) Evolution of the Human ASPM Gene, a Major Determinant of Brain Size. Genetics 165:2063-2070.