Blogs / The Loom

Time to print up some new business cards.

NOVA isn’t just a great television series; it’s also a formidable web site. (And, as with so many things media these days, it’s hard to draw the line between the two.)

They’ve just launched an evolution-rich site, with information on their evolution-related shows and lots of other goodies. (As you can see, it’s still beta.)

As part of the unveiling, NOVA asked me if I’d pick ten of the most important developments in evolutionary biology over the past decade. I came up with a far-from-exhaustive list. Check it out.

Check out this movie that uses Play Doh to explain the evolution of single-celled microbes to multicellular animals. It’s from Creature Cast, a very promising blog on biology from Casey Dunn of Brown University and his compadres.

CreatureCast Episode 2 from Casey Dunn on Vimeo.

I’ve written a few times here about the ongoing work of Joe Thornton, a biologist at the University of Oregon and the Howard Hughes Medical Institute. Thornton studies how molecules evolve over hundreds of millions of years. He does so by figuring out what the molecules were like in the distant past and recreating those ancestral forms in his lab to see how they worked. I first wrote about his work looking at how one molecule in our cells evolved from one function to another (here, here, and here). [Update: These links are now fixed.]

Most recently, I wrote in the New York Times about his latest experiment, in which he and his colleagues found that the evolution from the old function to the new one has now made it very difficult for natural selection to drive the molecule back to its old form. Its evolution has moved forward like a ratchet.

Thornton’s new work turned up last week on a web site run by the Discovery Institute, a clearinghouse for all things intelligent design (a k a the progeny of creationism). Michael Behe, a fellow at the Institute, wrote three posts (here, here, and here) about the new research, which he pronounced “great.”

This is the same Michael Behe who, when Thornton published the first half of this research, declared it “piddling.”

Why the change of heart? Because Behe thinks that the new research shows that evolution cannot produce anything more than tiny changes. And if evolution can’t do it, intelligent design can. (Don’t ask how.)

I pointed out Behe’s posts to Thornton and asked him what he thought of them. Thornton sent me back a lengthy, enlightening reply. Since the Discovery Institute doesn’t allow people to comment on their site, I asked Thornton if I could reprint his message here.

You may want to revisit my posts I linked to above to get a more detailed description of Thornton’s work before delving into Thornton’s reply. And while his reply is quite clear, there are a few terms that may be confusing, so let me preface it with a quick and dirty glossary of terms:

Cortisol: A hormone

Genetic drift: the change in the frequency of an allele (a version of a gene) in a population thanks to chance, not natural selection. Genetic drift can spread an allele through an entire population even if it provides no boost to reproductive success. It can even spread some mildly harmful ones under the right conditions

Glucocorticoid receptor: A receptor that binds cortisol. This is the molecule Thornton has studied, documenting the series of mutations that transformed it from an ancestral receptor sensitive to another hormone.

GR: Glucocorticoid receptor

Steroid receptors: A class of receptors that can bind steroids (a group of molecules that includes hormones such as cortisol).

And without further ado, here’s Thornton’s message–

**************

Dear Carl,

Thanks for asking for my reaction to Behe’s post on our recent paper in Nature.   His interpretation of our work is incorrect.  He confuses “contingent” or “unlikely”  with “impossible.”  He ignores the key role of genetic drift in evolution.  And he erroneously concludes that because the probability is low that some specific biological form will evolve, it must be impossible for ANY form to evolve.

Behe contends that our findings support his argument that adaptations requiring more than one mutation cannot evolve by Darwinian processes.  The many errors in Behe’s Edge of Evolution — the book in which he makes this argument — have been discussed in numerous publications.

In his posts about our paper, Behe’s first error is to ignore the fact that adaptive combinations of mutations can and do evolve by pathways involving neutral intermediates.  Behe says that if it takes more than one mutation to produce even a crude version of the new protein function, then selection cannot drive acquisition of the adaptive combination.

This does not mean, however, that the evolutionary path to the new function is blocked or that evolution runs into a “brick wall,” as Behe alleges.   If the initial mutations have no negative effect on the ancestral function, they can arise and hang around in populations for substantial periods of time due to genetic drift, creating the background in which an additional mutation can then yield the new function and be subject to selection.   This is precisely what we  observed in our studies of the evolution of the glucocorticoid receptor (GR).

In our 2007 paper in Science, we showed  that multiple mutations were indeed required for the GR to evolve its specificity for the hormone cortisol;  some of the mutations that trigger the change in function are deleterious if introduced in isolation, but others are “permissive”: they have no apparent effect on the function of the protein, but once they are in place the protein can tolerate the other mutations that shift and then optimize the new function.

By experimentally characterizing the functional effect of the key historical mutations in various combinations, we showed that there were indeed pathways from the ancestral protein to the new function that passed only through permissive and beneficial intermediate states.

A path to a new function that involves neutral intermediates is entirely accessible to the evolutionary processes of mutation, drift, and selection.  Our work showed that these classic neodarwinian processes are entirely adequate to explain the evolution of GR’s new function. (I should mention that pathways involving mildly deleterious intermediates are also accessible in reasonable time under some population genetic conditions; it’s just that their relative probability is lower than those involving neutral or beneficial intermediates.)

Behe’s discussion of our 2009 paper in Nature is a gross misreading because it ignores the importance of neutral pathways in protein evolution.  We studied whether the key mutations that drove the “forward” evolution of GR’s new function could be reversed in a later version of the GR, restoring the ancestral conformation and function.  We found that the later version of the protein could no longer tolerate the ancestral amino acids at these key sites, despite the fact that they had been present in the protein at an earlier stage of evolution.

We identified the specific “restrictive” historical mutations, which occurred after the shift in function, that either clashed with or failed to support the ancestral conformation. If these mutations are reversed first before the key function-switching mutations, the ancestral structure and function can be restored.

Reversing the restrictive mutations alone does not enhance the ancestral function, but in some orders they have no effect on the GR’s function.  These restrictive mutations are simply the flip-side of permissive mutations: reversal of a restrictive mutation is a permissive mutation for reverse evolution.  As Fig. 4  in our paper shows, there are several pathways back to the ancestral sequence that pass only through steps that are neutral or beneficial with respect to the protein’s functions.

Thus, all pathways to the ancestral sequence and structure are not blocked, as Behe says they are.  The chance effects of genetic drift could allow the protein to “float” along such paths, producing the appropriate background in which the function-shifting mutations could be reversed. However, selection alone would not be sufficient to drive the protein deterministically through the neutral steps. If selection for the ancestral function were imposed, reversal to the same sequence and conformation as the ancestor would be unlikely, though not impossible.

Taken together, the existence of permissive and restrictive mutations indicates that neutral paths to specific adaptive combinations of mutations are opening and closing during evolution.  If the clock could be turned back and history allowed to run again, it’s likely that some different path would be followed, and different protein forms would evolve by the natural processes of evolution.

This brings us to Behe’s second error, which is to confuse reversal to the ancestral sequence and structure with re-acquisition of a similar function.  We showed that restrictive mutations make selection alone insufficient to drive the protein back to the same form as that found in the ancestor.  But nothing in our results implies that, if selection were to favor the ancestral function again, the protein could not adapt by evolving a different, convergent, underlying basis for the function.

Indeed, directed evolution experiments in the laboratory have shown that mutation and selection alone can cause steroid receptor proteins to rapidly evolve sensitivity to new hormones; some of the mutations involved are different from those that occurred during the historical evolution of ancient proteins.

Our paper shows that re-evolution of the underlying ancestral form is unlikely, but it says nothing about the re-evolution of the ancestral function.  We found that chance processes play a key role in determining which adaptive forms actually evolve under selection, but this does not mean, as Behe alleges, that no adaptive form can evolve.

Finally, Behe erroneously equates “evolving non-deterministically” with “impossible to evolve.”  He supposes that if each of a set of specific evolutionary outcomes has a low probability, then none will evolve.  This is like saying that, because the probability was vanishingly small that the 1996 Yankees would finish 92-70 with 871 runs scored and 787 allowed and then win the World Series in six games over Atlanta, the fact that all this occurred means it must have been willed by God.

Consider the future: there are countless possible that could emerge from our present state, making the probability of the one that actually does evolve extraordinarily  low.  Does this mean that the future state that will ultimately emerge is  impossible?  Obviously not.  To say that our present biology did not evolve  deterministically means simply that other states could have evolved instead; it does not imply that it did not evolve.

Consider your own life history as an analogy.  We can all look back at the road  we have traveled and identify chance events that had profound effects on how our lives turned out.  “If the movie I wanted to see that night when I was 25 hadn’t been sold out,  I never would have gone to that party at my friend’s house, where I met my future spouse….”  Everyone can tell a story like this.  The probability of the life we actually lead is extraordinarily small.  That obviously doesn’t mean that its historical unfolding was impossible.

That we inhabit an improbably reality requires a divine explanation only if we, like Behe, take the teleological view that this is the only reality that could exist.  But if we recognize that the present is one of  many possibilities, then there is no difficulty reconciling the nature of  evolutionary processes with the complexity of biological forms. As history unfolds, potential pathways to different futures are constantly opening and  closing. Darwinian processes are entirely adequate to move living forms  along these pathways to a remarkable realization – but just one realization out of many others that could have, but didn’t, take place.

I considered hard whether I should address Behe’s argument or ignore it.  I am well aware that Behe and his supporters might portray my response as an indication that there is scientific debate over the possibility of adaptive protein evolution: “Look, an evolutionary biologist who actually does scientific research is arguing with me; let’s teach this controversy in public schools!”   Because Behe has grossly misinterpreted the results of my research to support his position, however, I feel some responsibility to set the record straight.

Behe’s argument has no scientific merit.  It is based on a misunderstanding of the fundamental processes of molecular evolution and a failure to appreciate the nature of probability itself.  There is no scientific controversy about whether natural processes can drive the evolution of complex proteins.  The work of my research group should not be misintepreted by those who would like to pretend that there is.

Best regards,
Joe

Deep down, we are all cannibals. In tomorrow’s issue of the New York Times, I take a look at the science of autophagy: how our cells destroy themselves to live again. It turns out that this cellular cannibalism is crucial for our well-being in many ways. Scientists are now trying to improve our ability to destroy ourselves as a potential treatment for diseases like cancer and Huntington disease, and perhaps even to slow the process of aging itself. Check it out.

(Note to link-lovers: the article takes you directly to some of the primary literature. Progress!)

[Image: Royal Academy of Arts]

Meet Ardipithecus.

This introduction has been a long time coming. Some 4.4 million years ago, a hominid now known as Ardipithecus ramidus lived in what were then forests in Ethiopia. Fifteen years ago, Tim White of Berkeley and a team of Ethiopian and American scientists published the first account of Ardipithecus, which they had just discovered. But it was just a preliminary report, and White promised more details later, once he and his colleagues had carefully prepared and analyzed all the fossils they had unearthed. “Later,” it turned out, meant 15 years.

I’ve mentioned before how unfashionable this slow-cooked style of science can be. But sometimes, it’s the only way to do things right. Getting clues about HIV by observing sick chimpanzees in the wild takes years.  And so does reconstructing a fossil–particularly one as delicate as Ardipithecus happened to be. Today, the journal Science has handed many of its pages over to White and his colleagues, who have filled them with lots of details about Ardipithecus, plus a couple excellent articles by writer Ann Gibbons. Ardipithecus has gone from being an enigmatic collection of bones to a new touchstone for our early hominid ancestors.

To appreciate the importance of this new look of Ardipithecus, you have to step back into the history of hunting for hominid fossils. In the early 1970s, Tim White was part of a research team that found what was, at the time, the oldest hominid known: a 3.2 million year old fossil of Australopithecus afarensis. What made their discovery particularly spectacular was that they found a fair amount of a single A. afarensis individual, whom they named Lucy.

Combined with other A. afarensis fossils, paleonthropologists got a pretty decent picture of what hominids looked like. Lucy was a chimpanzee-sized ape with a brain that was only a little bigger than a chimp’s. She still had long arms and curving hands and other traits hinting that she could still climb in trees. But she also had feet with stiff, forward-facing toes, an adaptation for walking on the ground.

So things stood for about 20 years. But then, with the discovery of Ardipithecus and a few other hominid fossils, the record of our ancestry got pushed back millions of years. The oldest fossil that’s been identified as a hominid, Sahelanthropus tschadensis, dates back between 6 and 7 million years old. But scientists have only found pieces of the Sahelanthropus skull. Another species, Orrorin tugenensis, is 6 million years old; it’s represented by little more than a leg bone.

Scientists have learned a lot from these pre-Lucy hominid fossils, but before now they weren’t able to make very detailed reconstructions of these creatures. Only about halfway along the journey from the first hominids to us did hominids come into full-bodied focus.

At first, Ardipithecus ramidus was yet another scrappy pre-Lucy fossil. The first report offered details about part of a 4.4 million-year-old jaw bone–a remarkable jaw bone, but just a jaw bone nonetheless. Soon after, White’s team found more fossil bones, from the hominid’s hand, skull, pelvis, feet, and on and on–110 pieces all told. But finding these pieces was just the start of the team’s labors. They picked away at the bits of rocks surrounding the fragile bits of fossils. They used a computer to manipulate CT-scans of the fossils to figure out how crushed fragments had originally fit together as a skull or a pelvis.

All this happened in strict secrecy. Some of us science writers knew a little about what the scientists were up to, but we could only guess when they’d finally finish working on the fossil. Sometimes when I’d speak to White, I’d inquire, and he’d politely say he wasn’t done yet.

Looking at the papers out today in Science, you can see that they’ve been very busy. I won’t even try to offer an all-encompassing account of their new results. In many cases, it wouldn’t actually be worth the effort, because these papers are just the first salvo in what will be a fascinating debate about how our ancestors evolved. I was speaking to University of Wisconsin paleoanthropologist John Hawks yesterday on another subject, and he was giddy about the papers’ imminent publication. “Tomorrow’s Christmas!” he said. (His young son overheard him on the phone and got very excited and confused. I had to give Hawks a few minutes  to explain the nature of metaphor. Not sure how well that went over.)

For now, I’ll point out a few of the results on Ardipithecus that are particularly intriguing.

Nice Guys With Little Teeth

Those of you reading this post that have a Y chromosome have canine teeth that are about the same size as those of my XX readers. The same rule applies to the teeth of some other primate species. But in still other species, the males have much bigger canines than the females. The difference corresponds fairly well to the kind of social lives these primates have. Big canines are a sign of intense competition between males. Canine teeth in some primate species get honed into sharp daggers that males can use as weapons in battles for territory and for the opportunity to mate with females.

Men have stubby canines, which many scientists take as a sign that the competition between males became less intense in our hominid lineage. That was likely due to a shift in family life. Male chimpanzees compete with each other to mate with females, but they don’t help with the kids when they’re born. Humans form long-term bonds, with fathers helping mothers by, for example, getting more food for the kids to eat. There’s still male-male competition in our lineage, but it’s a lot less intense than in other species.

White and his colleagues  found so many teeth of different Ardipithecus individuals that they could compare male and female canines with some confidence. The male teeth turn out to be surprisingly blunted. This result suggests that hominids shifted away from a typical ape social structure early in our ancestry. If this was a result of males forming long-term bonds with females and helping raise young, this shift was able to occur while hominids were still living a very ape-like life. Ardipithecus existed about 2 million years before the oldest evidence of stone tools, suggesting that technology was not the trigger for the evolution of nice hominid guys.

Walking, Of A Sort; And Climbing, Of A Sort

C. Owen Lovejoy of Kent State University spearheaded the studies on how Ardipithecus moved. He and his colleagues argue that its pelvis could support its upper body during bipedal walking. It wasn’t a fabulous walker, and was probably a terrible runner. Nevertheless, it had some of the same anchors for muscles that we have on our pelvis, and which chimpanzees and other apes lack. Its pelvis was, in other words, a mosaic. Lucy, we now can see, represents a later step in the journey towards out own walking-adapted anatomy.

Ardipithecus’s feet were mosaics too. The four little toes were adapted for walking on the ground. Yet the big toe was still opposable, much like our thumbs. This sort of big toe helped Ardipithecus move through the trees much more adeptly than Lucy.

But Ardipithecus could not climb through trees as well as, say, chimpanzees. Chimpanzees have lots of adaptations in their arms and shoulders to let them hang from branches and climb vertically up trees with incredible speed. Ardipithecus had hands were not stiffened enough to let them move like chimpanzees. Ardipithecus probably moved carefully through the trees, using its hands and feet all at once to grip branches.

Just a Reminder: We Didn’t Evolve From Chimpanzees

Chimpanzees may be our closest living relatives, but that doesn’t mean that our common ancestor with them looked precisely like a chimp. In fact, a lot of what makes a chimpanzee a chimpanzee evolved after our two lineages split roughly 7 million years ago. Ardipithecus offers strong evidence for the newness of chimps.

Only after our ancestors branched off from chimpanzees, Lovejoy and his colleagues argue, did chimpanzee arms evolve the right shape for swinging through trees. Chimpanzee arms are also adapted for knuckle-walking, while Ardipithecus didn’t have the right anatomy to lean comfortably on their hands. Chimpanzees also have peculiar adaptations in their feet that make them particularly adept in trees. For example, they’re missing a bone found in monkeys and humans, which helps to stiffen our feet. The lack of this bone makes chimpanzee feet even more flexible in trees, but it also makes them worse at walking on the ground. Ardipithecus had that same foot bone we have. This pattern suggests that chimpanzees lost the bone after their split with our ancestors, becoming even better at tree-climbing.

Chimpanzees do still tell us certain things about our ancestry. Our ancestors had chimp-sized brains. They were hairy like chimps and other apes. And like chimps, they didn’t wear jewelry or play the trumpet.

But then again, humans turn out to be a good stand-in for the ancestors of chimpanzees in some ways–now that Ardipithecus has clambered finally into view.

[Reconstructions: Copyright 2009, J.H. Matternes. Cover: Copyright 2008 T.H. White]

I had a sudden drop in blood pressure when I checked out the new issue of Nature today. Evolutionary biologist Laurence Hurst wrote a two-book review: Richard Dawkins’s The Greatest Show on Earth, and my own The Tangled Bank. I revived when I saw that my book held up under Hurst’s comparison: “The book is billed as the first textbook on evolution for the general reader, and in that framework, it excels.”

Hurst used his review to pose an interesting question. He contrasts my style, which he describes as “authoritative and easy to read” with that of Dawkins, who “emerges like a prize-fighter, knocking out of the ring all objections.” Hurst then asks, “So which is the better strategy for explaining the difference between fact and fantasy, that of the quiet American or that of the British Rottweiler?”

Here’s my answer: this is a false choice. Dawkins and I did not write the same kind of book. Mine is a textbook, and Dawkins’s is not. Reading Hurst trying to equate the two gave me a vision of a college class on evolution. Spotlights swirl around the lecture hall. The professor jogs in. He’s wearing gold trunks and boxing gloves. As he pumps his arms over his head, Gary Glitter blares from the loudspeakers.

“Who here doesn’t think there are any transitional forms in the fossil record?” he roars.

One student meekly raises his hand, and immediately receive a devastating left hook. As he fades out of consciousness, he hears the professor bellowing his trademark battle-cry, “Ambulocetus!”

I can’t speak about Dawkins’s latest book, not having read it yet. But I can speak to my own thinking as I wrote The Tangled Bank. I envisioned my potential readers as curious people who didn’t know much about evolution–what the idea actually is and how scientists study it. I envisioned people who might be interested in learning the nuts and bolts of processes like selection and drift, and who might be intrigued by sexually deceptive wasps, whales with legs, the viruses that dominate our genome, and other features of life that evolution allows us to understand. My readers may not hear Gary Glitter in their mental loudspeakers as they work their way through my book. But, if I succeed, the music should still be sweet.

Three years ago, I wrote a series of blog posts about how scientists at the University of Oregon reconstructed the 450-million-year history of a protein. You can read the posts here, here, and here. What was particularly elegant about the study was how the scientists recreated the ancestral protein as it existed over 400 million years ago, to see how it functioned. Then they  pinpointed the mutations that transformed the protein, shifting it from an old function to a new one.

Recently, the scientists tried to run their experiment backwards. They tried to turn the new protein back into the old one. And they failed. In that failure, they’ve discovered something important. They argue that when it comes to evolution, you can’t go home again.

In today’s issue of the New York Times, I describe this new research, which was recently published in Nature. (Check out the web page of the lead author, Joseph Thornton, for pdf’s of all his papers on this paleoprotein project.)

Congratulations to all the Macarthur genius grant winners announced today. Their ranks include two evolutionary biologists.

1. Beth Shapiro, at Penn State, studies ancient DNA to understand extinct critters like mammoths and dodos. I’ve embedded a lecture I saw her give over the summer below. [Update: Sorry, sorry--Penn State, not Penn!]

Another winner is Richard Prum from Yale, who I had fortuitously asked to come talk to my writing class this morning. I had my students interview him for a profile. Voila, instant news hook!

The poor students. They were overwhelmed by the torrent of work Prum described, from the sophisticated optical properties of bird feathers to the origin of birds among the dinosaurs to the deep unity of biology and aesthetics. I’ve embedded the Macarthur’s video of Prum from their 2009 Fellows site, where he talks a bit about his stuff.

Recently I took a trip down to North Carolina to spend some time with Brian Hare, an anthropologist at Duke University who wants to understand how human nature evolved. While Hare spends a lot of time in Africa studying chimpanzees and bonobos, he also studies dogs. The social intelligence of dogs is not just interesting in itself, but also for the clues it offers about how we evolved. It’s possible that wolves became dogs in much the same way our chimp-like ancestors became human.

In the newest issue of Time, I’ve written a feature about canine cognition, and scientists like Hare who are trying to plumb its depths. Check it out.

(And be sure to also check out the photoessay of Hare’s new Center for Canine Cognition at Duke, from which this picture comes.)

Romantic poetry and developmental biology have something in common: Goethe. One of botany’s lesser known pioneers, Goethe actually wrote a visionary essay about plants in 1790, which can be summed up in his motto, “All is leaf.” Scientists who are studying the evolution of flowers today hear the echoes of his words. To find out more, check out my lead story in the Science Times section of the New York Times today.

And for more information, check out these recent reviews–

The Evolution of Petal Identity

Reconstructing the ancestral angiosperm flower and its initial specializations

The meaning of Darwin’s ‘abominable mystery’
Reconstructing the ancestral female gametophyte of angiosperms: Insights from Amborella and other ancient lineages of flowering plants

Charles Darwin was interested not just in how new things evolve, but also in how old things disappear. Often, they don’t disappear completely without a trace. We don’t have a visible tail like our primate ancestors did, but we still have a series of little bones tucked away at the bottom of the spine. While it may not function like a full-blown tail, it still anchors muscles around the pelvis. Blind cavefish may not have eyes of the sort found on their cousins in the outside world, but they still start to develop eyes as larva, before the cells start to die away.

Sometimes, though, the only place to look for vestiges of a lost trait is in a genome.

In the journal PLOS Genetics, Mark Springer of the University of California and his colleagues have published an intriguing study of how teeth–and the genes for teeth–have faded away over the past 50 million years. In particular, they looked at enamel, the tough covering that caps the teeth of humans and other vertebrates.

Enamel has three advantages for this kind of study: one is that it fossilizes well. For a lot of species, enamel is often the only thing left behind. Another advantage of enamel is that scientists also have a good understanding of the genes that build it–genes that are similar across a wide range of species. And the third advantage of enamel is that certain lineages of mammals have lost it. Baleen whales, anteaters, and pangolins have all lost their teeth entirely. (Baleen whales grow tooth buds, like cave fish grow eyes, but the buds die back without ever forming enamel.) Sloths, armadillos, pygmy sperm whales, and aardvarks still have teeth, but have no enamel left. This pattern suggests that enamel has been lost independently in several lineages of mammals.

In each lineage, these mammals have lost enamel as they’ve shifted away from depending on hard teeth. As I wrote about here, baleen whales descend from ancestors with formidable teeth for catching prey. But then their ancestors evolved a new way to eat, growing baleen–frond-like sheets of tissue that can filter out krill and other small animals from sea water. As anteaters came to only eat insects, the teeth of their ancestors became not just pointless but a hindrance. Their mouth became finely adapted for shooting a long tongue forward into ant nests. Big teeth would just get in the way.

So where did the enamel go? The scientists decided to test the possibility that the genes for enamel were still in the genomes of toothless mammals, but they had been shut down. In each species’s genome, scientists find a number of so-called pseudogenes, which can no longer encode a protein because of a crippling mutation. A mutation may, for example, insert a “stop” command, so that cells can no longer read the full sequence of a gene and make a full protein. Other mutations can shift a big chunk of DNA over a couple positions, garbling the code. Imagine shifting all the spaces in a sentence to the left. Y ouwou ldg etsomethi ngli kethis.

Despite these devastating mutations, pseudogenes often manage to retain a strong resemblance to their working counterparts. We, for example, have hundreds of pseudogenes that show a striking resemblance to hundreds of other genes that encode a variety of receptors in our noses. So Springer and his colleagues sequenced an enamel-building gene called ENAM in 49 mammal species, including toothless or enamel-less ones to see what happened to the gene along the way.

Their results were pretty much what they expected, but they’re still pretty amazing. There were no frameshift mutations in ENAM among the mammals with teeth. But 17 out of 20 species without teeth or enamel had at least one. In all 20 enamel-free species, a stop command (known as a stop codon) was present. These genes are shot.

The scientists then probed the evolution of the ENAM genes by taking advantage of the fact that only some letters in a gene encode a protein and others are ignored. Mutations that change the structure of a protein may have serious effects on an animal. They may be good effects or really bad ones–in either case, they may change the overall reproductive success of individuals who carry the mutation. On the other hand, silent mutations may have no effect (or at least just a small one).

It turns out that in mammals with teeth, the ENAM gene has experienced something call purifying selection. In other words, very few protein-changing mutations have endured for millions of years because tinkering with the recipe for enamel is a really bad thing to do if you need hard teeth to survive. In mammals without enamel, on the other hand, the ENAM gene evolved in a different way. It experienced what’s known as neutral evolution: the silent mutations and the protein-changing ones have occurred at about the same rate. It just doesn’t matter to the mammals anymore, because the genes are, as I mentioned before, shot.

These genomic vestiges don’t just provide evidence of how teeth were lost. They also provide some clues to when they were lost. By comparing closely related species that don’t have enamel, the scientists could tally up the mutations that had arisen since their last common ancestor. And since neutral mutations tend to pile up at a fairly steady rate, the scientists were able to estimate how long ago the ENAM gene turned from an essential gene to a useless one. In some cases, the scientists predict, paleontologists will find toothless members of these lineages millions of years older than the oldest known fossils without teeth–such as with pangolins, as this figure illustrates.. It is a remarkable convergence, of traces of history recorded in molecules tucked away in anteater cells, and skulls that have managed to turn to stone. But from them, a single picture emerges.