Dead genes for tooth enamel

September 10, 2009 • 5:52 pm

Vestigial organs are commonly cited as evidence for evolution; indeed, I wrote most of a chapter about them in WEIT. And although some of these organs may have a function (the appendix, for example, is now thought to play a small role in the immune system), the fact of functionality doesn’t detract from their vestigiality — or their usefulness as evidence for common ancestry. The fact that the penguin’s “wings” now serve as flippers doesn’t mean that they say nothing about penguins’ ancestry from birds that could fly. (My own definition of a vestigial trait is loosely “a trait that now serves a function completely different from what impelled its initial evolution, and for which traces of its original structure still remain.”)

And, anyway, some vestigial organs appear to have no function at all. You’d be hard pressed to claim that there was a function for the tiny nub-like wings of the kiwi bird, buried deep within the feathers on its flanks.

But you’d be even harder pressed to argue that dead genes have a function.

One of the predictions of evolution is that if vestigial organs exist, then surely vestigial genes must exist, for traits that shrink or disappear must surely be based, at least sometimes, on genes that disappear. But genes aren’t just snipped out of the DNA when they’re no longer needed: natural selection will inactivate them, usually by favoring a mutation that removes one or a few DNA bases (a deletion), putting in a “stop codon” (a change in the DNA that prematurely terminates the protein being read from that DNA’s code, making a “frameshift” mutation (changing the triplet code so that the entire coding frame of a DNA sequence is thrown off), or changing the regulatory region of a gene so its protein is no longer made. But the remnants of the gene will remain in the DNA, testifying to its ancestry from a gene that was active in an ancestor. These dead genes are called pseudogenes.

Now that genome sequencing is routine, evolutionists can do large-scale searches for dead genes. And, as predicted, they’re all over the place — in nearly every species that has been examined. Some of the “dead” genes I discuss in WEIT include human genes that used to make vitamin C or egg yolk in our ancestors, but have now been rendered mute. It would be hard to argue that these genes still have a “function,” for they produce no protein at all. Their existence is a powerful argument in favor of evolution and against creationism.

A new paper in PLoS Genetics continues the search for predicted dead genes — this time for genes that once made tooth enamel — and finds a lot of these wrecks. They’re exactly where you expect to find them — in toothless animals long thought to have descended from animals with teeth. So the “theory” of evolution is once again confirmed, although we hardly need further confirmation. But this paper goes beyond a mere redudant proof of common ancestry. The authors also make models of how the “enamel” genes degenerated, and, by calculating when this degeneration happened, predict what the teeth of common ancestors should look like. This prediction is in principle testable by finding the relevant fossils and looking at their teeth.,

There are two kinds of mammals that lack tooth enamel: those that are completely toothless (e.g., armadillos, pangolins, aardvarks, baleen whales), and those that have teeth that lack enamel (e.g., dwarf sperm whales, two-toed sloth). From other evidence, including fossils and comparative morphology, scientists have confidently predicted that every one of these species descended from ancestors that had enameled teeth. The researchers sequenced, in many mammals species, the critical gene enamelin (ENAM), which helps deposit hydroxyapetite into the tooth. If ENAM is knocked out in mice, enamel doesn’t form.

Sure enough, in every species lacking teeth or enameled teeth, ENAM was rendered nonfunctional, either by the accumulation of frameshift mutations or stop codons. The authors give a very nice graph of how the genes have degenerated in each lineage, which I show below (the caption is at the bottom of this post if you’re a geneticist).

Mammal teeth

Figure 1. Enamelin gene phylogeny for mammal species with no teeth, un-enameled teeth, or fully enameled teeth (tooth type illustrated at right, before species name). Caption for this figure, showing the various genetic changes that have inactivated ENAM, is at the bottom of this post.

Well, that’s evidence for evolution and common ancestry, and it’s neat. But we hardly need more evidence of this type to support Darwinism, because there are many such reports of pseudobenes. What makes the paper unique is the authors’ model of how and when ENAM was inactivated in several lineages.

The details are complicated, but in essence the authors modeled a two-step process of gene evolution: before the mutation inactivating ENAM (whose occurrence can be estimated from the gene tree), and thereafter. Before inactivation the gene was assumed to evolve slowly since gene changes were largely deleterious. After inactivation, the gene evolved faster — since it was no longer making a useful product, changes were assumed to accumulate “neutrally” (that is, all changes carried neither selective penalty nor advantage). This analysis made several predictions. One of them is that ancestral xenarthans (armadillos, sloths, and anteaters), had teeth with enamel, even though living representatives don’t. This is a testable prediction: find early ‘basal” xenarthans, and look at their teeth.

You may have noticed that after the gene was inactivated, it was assumed to degenerate through the accumulation of random, neutal mutations. This is a valid assumption for gene inactivation, but not necessarily for the disappearance or shrinkage of entire traits. If a trait is no longer useful, there are actually three ways it can degnerate:

1. As posited for genes, the accumulation of inactivating mutations, which carry no penalty since they affect a trait that makes no contribution to reproduction.

2. Traits can degenerate through positive natural selection. One way is simply that an animal (or plant) can be seen as an economic compromise among biological materials, and if you don’t need a feature, selection can favor rerouting its building blocks to other features. The material used to build the wing of a flightless bird, for example, could be diverted to making or strengthening bones in other parts of the body.

3. Likewise, traits that are no longer useful might be easily injured. Selection would then favor degeneration of that trait as a way of preventing injury. This may, for example, explain the reduced eyes of cave fauna or burrowing animals like moles.

It isn’t easy to distinguish between these hypotheses. One way is to find a bunch of genes involved in the trait’s degeneration and, by sequencing them, see if the DNA has changed by natural selection since the trait was no longer useful. (There are statistical tests for this, though they have some problems.)

Meredith RW, Gatesy J, Murphy WJ, Ryder OA, Springer MS (2009). Molecular decay of the tooth gene enamelin (ENAM) mirrors the loss of enamel in the fossil record of placental mammals. PLoS Genet 5(9): e1000634. doi:10.1371/journal.pgen.1000634

Caption for Fig. 1 (above), from Meredith et al.: Figure 1. Species tree with frameshift mutations and dN/dS branch coding. Symbols next to taxon names denote taxa having teeth with enamel, taxa having teeth without enamel, and edentulous taxa. Branches are functional (black), pre-mutation (blue), mixed (purple), and pseudogenic (red). Vertical bars on branches represent frameshift mutations (see Table S1). Frameshifts that map unambiguously onto branches are shown in black. Frameshifts shown in white are unique, but occur in regions where sequences are missing for one or more taxa (Figure S7) and were arbitrarily mapped onto the youngest possible branch. Homoplastic frameshifts (deltran optimization) are marked by numbers. Numbers after taxon names indicate the minimum number of stop codons in the sequence (before slashes) and the length of the sequence (after slashes).

38 thoughts on “Dead genes for tooth enamel

  1. Outstanding! (I started to write fantastic but then decided some literalist might come along thinking that I was accusing the whole thing of being fantasy).

  2. “The material used to build the wing of a flightless bird, for example, could be diverted to making or strengthening bones in other parts of the body.”

    Aha! So we have an Intelligent Diverter! Talk your way out of that, wise guy.

    :- )

    1. There actually is a great example of that kind of thing – the lens crystallins are the example I know. At least many of the proteins that form the eye lens are catalytically inactive forms of metabolic enzymes, and they aren’t the same ones as you go from one to another species. NAD-binding dehydrogenases seem to be the favorite sort of protein, and as far as I know there is no agreement on why this should be, altho UV protection through absorption by the coenzyme is one thought. And perhaps for some reason those proteins afford just the right transparency or refractive index.

      The example I know best is that the zeta-crystallin of elephant shrew is an aldehyde dehydrogenase. There, the catalytic cysteine is something else (serine as I recall), so it comes from its own gene.

      Joram Piatigorsky is the name behind much of this work, or at least the one to turn to first, if anyone’s interested. Search protein recruitment piatigorsky for lots of hits. (A quick skim of some of those hits shows that this is the case in octopuses as well! If I remember correctly that they are one of the examples of independent eye evolution, how’s that for convergence!)

  3. I have seen another writeup of this paper elsewhere but I like the depth you covered it, Jerry.

    One small nit to pick:

    …evolutionists can do large-scale searches…

    I don’t like the word ‘evolutionists”. I would prefer seeing ‘evolutionary biologists’ or ‘evolutionary scientists’ instead.

    1. Perhaps being an “evolutionist” is nothing to be ashamed of. ;^)

      I’m only on chapter 2 of WEIT, and already I’m beginning to suspect there is something to all this evolution businness.

      Also, great write-up as usual, Jerry.

    2. Great article, but I agree that “evolutionist” isn’t the best word. Evolutionary biologist, or just biologist, would be better IMHO. It is used too often used by creationist to equate acceptance of evolution to belief in creationism.

  4. I’ve always wondered whether selection plays a significant role in the degeneration of neutral traits. Neutral mutations (your scenario 1) seem capable of doing the job in pretty much all cases, but is there evidence that natural selection (whether 2 or 3) helped along importantly sometimes? How would one go about testing that?

  5. Not only is there a vestigial spandrel between my manual and electric toothbush; I’ve got an unintelligently designed orthognathic retainer to assist my proteoglycans (drum roll).

  6. Fantastic, Jerry (and the team who wrote the PLoS Genetics article). This one goes straight into my university First Year lectures on evolution, starting in 3 weeks time…

  7. “Now that genome sequencing is routine, evolutionists can do large-scale searches for dead genes. And, as predicted, they’re all over the place — in nearly every species that has been examined.”

    The word nearly is throwing me off. Are there species in which no pseudogenes are found?

  8. My own definition of a vestigial trait is loosely “a trait that now serves a function completely different from what impelled its initial evolution, and for which traces of its original structure still remain.”

    Isn’t there something circular about this definition? If vestigial organs are to be used as evidence for evolution, it doesn’t make sense to define them in a way that assumes evolution to be true.

    1. And would that “definition” include birds’ wings? Or are we going to say that legs and wings are both about locomotion, so it’s not a matter of being “completely different,” despite the fact that flight is so very different from either walking or for what bipedal dinosaurs used their forelimbs?

      Perhaps it would be even better to recognize that “vestigials” are really only a “special case” of homology. I don’t consider penguins’ flippers to be vestigial at all, in fact (used for locomotion), but that comes down to a matter definition. In the end, since it’s all about homology anyway, kiwi wings are homologous with those of flying birds, yet are clearly closer to the traditional notion of “vestigial” than are something like penguins’ flippers.

      There will never be a clear definition of “vestigial,” iow, so calling penguins’ flippers “vestigial” might work (unlike most auks’ wings, they do not remain useful for flight at any rate). I’d still have trouble seeing how evolution of wings into flippers should be categorized differently from, say, the evolution of terrestrial limbs into flippers–which generally is not considered “vestigial.”

      Glen Davidson

      1. I agree that vestigial organs are simply a special case of homology. They are clearly homologous to other organs, with the addition that they are in a degenerated state, and of little or no contribution to reproduction. As Jerry said, evidence for degeneration can be found by looking at the genes that code for proteins involved in those traits (which should be pseudogenes) and by looking at development (for example, as Darwin noted, vestigial features are proportionally larger in the embryo).

    2. Let me back up here to get “evolution” out of it. Redefinition: “A trait that is now either completely useless, or that serves a function completely different from what it once had, but for which traces of its original use still remain.” This presupposes only an original “use” rather than a “use that evolved.”

    3. If vestigial organs are to be used as evidence for evolution, it doesn’t make sense to define them in a way that assumes evolution to be true.

      It doesn’t make sense, but not because it would be a problem for testing IMO.

      Formal theories are a very small part of the larger algorithmic universe that seems to be nature and/or science itself. Testing means that there is no problem with tautologies (which would be true, but not add information) or circle argumentation (because after all a theory is essentially a tautology based on and predicting its data and an isolated ad hoc hypothesis even more so). If it passes testing, by definition it works.

      The problem here is that one should never assume and use more than is necessary, whether in making sound theory or making sound predictions. Thanks for the heads up.

  9. Great blog you have here. I’ll be a regular poster from here on out, to be sure. While tooth enamel genetics isn’t my main area of interest, I love all of biology with a passion. When you post anything relating to insects or reptiles / amphibians I’ll be all over it.

    I hope you don’t mind me posting links to this place when I talk to evolution deniers, which I do rather frequently. Thanks for ‘creating’ it. You’ve designed it intelligently, to be sure.

    “Religion is most like a computer virus for brains. It comes complete with instructions for development and propagation of the virus, and code that prevents the person from deleting it or noticing that it doesn’t conform to reality. It is orchestrated, organized, and officially sanctioned psychosis, made easily digestible and palatable to the masses.”
    -Saint Brian the Godless

  10. I would define “vestigal” as ‘no longer useful for its original purpose, with the qualifier of mentioning the original purpose in the statement. So vestigal legs may become functioning wings, but they’re still vestigal legs. So if the wings ever evolve into say, flippers, they’re now vestigal legs that evolved into vestigal wings which are now functioning flippers. Seems logically consistant, no?

    “If any hypothetical belief system dislikes science, which is without a doubt the best method of finding the truth about reality that we have ever come up with, the next question is naturally “What do they have to fear from the truth?””
    -Saint Brain the Godless

    1. The numbers next to posts only appear next to “subject” posts. When people respond to someone’s post, it is not numbered but it is counted in the total number of posts.

      So if there are new posts but no new numbered posts, then the new posts were in response to older posts.

      1. And once in a while, it counts wrong. I have seen only one post and it reports two.

        I think it is fueled by quantum Mechanics (Heisenberg uncertainty principle) 🙂

  11. because there are many such reports of pseudobenes.

    I see what you did there (but I repeat myself.

    Can we pleeeeeaaaaaassssse have a post on pangolins? They look absolutely adorable! Far more so than icky cephalopods.

    1. Pangolins are way cool, no doubt about it.

      Hey, if he’ll play requests I vote for the rabbit or sheep liver fluke with it’s triple-host parisitic life cycle of mammal-snail-ant. How it takes control of an ant like in “Invaders of the Body Snatchers” and gets it to sacrifice itself, getting eaten by the rabbit or sheep etc. Takes control of its brain in essence, or so it seems. I’ve always thought that it would have been a better thing for creationists to talk about rather than the flagellum or the eye. Perfectly explicable by normal process of evolution of course, but still, weirder by far than eye or flagellum.

      Of course, I’m perfectly happy with whatever he wishes to write.

      1. Cretinists tend not to want to dwell on “design” that makes the “designer” look like an inventive sadist.

      2. Actually, and sadly, they are adept at spinning this as an argument FOR a designer just as they’ve been spinning crap into “higher truths” for years:

        Tongue-eating isopod (Cymothoa exigua). This small crustacean feeds on the tongue of the rose snapper, its host fish. The snapper’s tongue eventually atrophies and degenerates from this activity. The isopod then uses advanced hook-like structures to attach itself to the fish’s mouth, remaining there and acting as a replacement tongue (while getting first shots at any incoming meals).

        This bizarre creature from the depths of the Gulf of California points out God’s…interesting sense of humor. But it’s also a nasty problem for evolution. The isopod’s anchoring mechanism, instincts, and ability to skillfully avoid being eaten as it feasts on the fish’s tongue (and later, steals food) requires an intelligent designer to explain.

        (HT/ to Monado FCD at Pharyngula)

        I agree it speaks more of a sadistic designer than an intelligent one.

    2. Yes, (pretty please) post cute things like pangolins.

      –I have to erase the vision of that horrible tongue-eating parasite that PZ posted. Vomitous. *shudders*

  12. IIRC the mouth was developed as the 2nd body opening for a digestive system?! (Or maybe that is just a specific of fetal development?) If so, presumably then the first opening was bidirectional. Does this mean that my ass is a vestigial mouth?

    Or is it just Dembski’s?

    This may, for example, explain the reduced eyes of cave fauna or burrowing animals like moles.

    Hmm. I seem to remember a blog post about research coupling the degeneration of eyes on cave fishes with their developing better sense mechanisms.

    Anyway, not being a biologist, isn’t such a mechanism part of the natural selection class? Whether the regulatory function was able to change or functions for they eye was as the article says diverted (by gene copying and later destruction of the nonfunctional gene, or whatever).

    1. Your spelling and grammar lead me to conclude that you are either a child, or one of those homeschool creationists.

Leave a Reply