Your hands are, roughly speaking, 360 million years old. Before then, they were fins, which your fishy ancestors used to swim through oceans and rivers. Once those fins sprouted digits, they could propel your salamander-like ancestors across dry land. Fast forward 300 million years, and your hands had become fine-tuned for manipulations: your lemur-like ancestors used them to grab leaves and open up fruits. Within the past few million years, your hominin ancestors had fairly human hands, which they used to fashion tools for digging up tubers, butchering carcasses, and laying the groundwork for our global dominance today.
We know a fair amount about the transition from fins to hands thanks to the moderately mad obsession of paleontologists, who venture to inhospitable places around the Arctic where the best fossils from that period of our evolution are buried. (I wrote about some of those discoveries in my first book, At the Water’s Edge.)
By comparing those fossils, scientists can work out the order in which the fish body was transformed into the kind seen in amphibians, reptiles, birds, and mammals–collectively known as tetrapods. Of course, all that those fossils can preserve are the bones of those early tetrapods. Those bones were built by genes, which do not fossilize. Ultimately the origin of our hands is a story of how those fin-building genes changed, but that’s a story that requires more evidence than fossils to tell.
A team of Spanish scientists has provided us with a glimpse of that story. They’ve tinkered with the genes of fish, and turned their fins into proto-limbs.
Before getting into the details of the new experiment, leap back with me 450 million years ago. That’s about the time that our early vertebrate ancestors–lamprey-like jawless fishes–evolved the first fins. By about 400 million years ago, those fins had become bony. The fins of bony fishes alive today–like salmon or goldfish–are still built according to the same basic recipe. They’re made up mostly of a stiff flap of fin rays. At the base of the fin, they contain a nubbin of bone of the sort that makes up our entire arm skeleton (known as endochondral bone). Fishes use muscles attached to the endochondral bone to maneuver their fins as they swim.
Our own fishy ancestors gradually modified this sort of fin over millions of years. The endochondral bone expanded, and the fin rays shrank back, creating a new structure known as a lobe fin. There are only two kinds of lobe fin fishes left alive today: lungfishes and coelacanths. After our ancestors split off from theirs, our fins became even more limb like. The front fins evolved bones that corresponded in shape and position to our ulna and humerus.
A 375-million-year-old fossil discovered in 2006, called Tiktaalik, had these long bones, with smaller bones at the end that correspond to our wrist. But it still had fin rays forming fringe at the edges of its lobe fin. By 360 million years ago, however, true tetrapods had evolved: the fin rays were gone from their lobe fins, and they had true digits. (The figure I’m using here comes from my more recent book, The Tangled Bank.)
Both fins and hands get their start in embryos. As a fish embryo grows, it develops bumps on its sides. The cells inside the bumps grow rapidly, and a network of genes switches on. They not only determine the shape that the bump grows into, but also lay down a pattern for the bones which will later form.
Scientists have found that many of the same genes switch on in the limb buds of tetrapod embryos. They’ve compared the genes in tetrapod and fish embryos to figure out how changes to the gene network turned one kind of anatomy into the other.
One of the most intriguing differences involves a gene known as 5′Hoxd. In the developing fish fin, it produces proteins along the outer crest early on in its development. The proteins made from the gene then grab other genes and switch them on. They switch on still other genes, unleashing a cascade of biochemistry.
Back when you were an embryo, 5′Hoxd also switched on early in the development of your limbs. It then shut off, as it does in fish. But then, a few days later, it made an encore performance. It switched back on along the crest of the limb bud a second time. This second wave of 5′Hoxd marked a new pattern in your limb: it set down the places where your hand bones would develop.
Here, some scientists proposed, might be an important clue to how the hand evolved. It was possible that mutations in our ancestors caused 5′Hoxd to turn back on again late in development. As a result, it might have added new structures at the end of its fins.
If this were true, it would mean that some of the genetic wherewithal to build a primitive hand was already present in our fishy ancestors. All that was required was to assign some genes to new times or places during development. Perhaps, some scientists speculated, fishes today might still carry that hidden potential.
Recently Renata Freitas of Universidad Pablo de Olavide in Spain and her colleagues set out to try to unlock that potential. They engineered zebrafish with an altered version of the 5′Hoxd gene, which they could switch on whenever they wanted by dousing a zebrafish embryo with a hormone.
The scientists waited for the fishes to start developing their normal fin. The fishes expressed 5′Hoxd at the normal, early phase. The scientists waited for the gene to go quiet again, as the fins continued to swell. And then they spritzed the zebrafish with the hormone. The 5′Hoxd gene switched on again, and started making its proteins once more.
The effect was dramatic. The zebrafish’s fin rays became stunted, and the end of its fin swelled with cells that would eventually become endochondral bone.
These two figures illustrate this transformation. The top figure here looks down at the back of the fish. The normal zebrafish is to the left, and the engineered one is to the right. The bottom figure provides a close-up view of a fin. The blue ovals are endochondral bone, and the red ones display a marker that means they’re growing quickly.
One of the most interesting results of this experiment is that this single tweak–a late boost of 5′Hoxd–produces two major effects at once. It simultaneously shrinks the outer area of the fin where fin rays develop and expands the region where endochondral bone grows. In the evolution of the hand, these two changes might have occurred at the same time.
It would be wrong to say that Freitas and her colleagues have reproduced the evolution of the hand with this experiment. We did not evolve from zebrafishes. They are our cousins, descending from a common ancestor that lived 400 million years ago. Ever since that split, they’ve undergone plenty of evolution, adapting to their own environment. As a result, a late boost of 5′Hoxd was toxic for the fishes. It interfered with other proteins in the embryos, and they died.
Instead, this experiment provides a clue and a surprise. It provides some strong evidence for one of the mutations that turned fins into tetrapod limbs. And it also offers a surprise: after 400 million years, our zebrafish cousins still carry some of the genetic circuits we use to build our hands.
Freitas et al, “Hoxd13 Contribution to the Evolution of Vertebrate Appendages.” Developmental Cell dx.doi.org/10.1016/j.devcel.2012.10.015
Schneider and Shubin, “Making Limbs from Fins.” Developmental Cell dx.doi.org/10.1016/j.devcel.2012.11.011
Jad Abumrad and Robert Krulwich have a new episode of Radiolab airing this week. The theme of the show is heredity and its attendant mysteries. I had great fun telling the strange and tragic story of the early twentieth century biologist Paul Kammerer, who thought he could change the human race with the help of a midwife toad. (Some of my favorite sources about this tale and its present-day reverberations are here, here, here, here, here, and here.)
Science writer Sam Kean joins the Radiolab crew as well, along with some scientists doing fascinating work on mother rats licking baby rats, Swedes surviving harsh winters, and more.
Added bonus: my daughters Charlotte and Veronica helped read the program credits. They get their ability to pronounce “Jad Abumrad” from me.
I’ve embedded the show below–
Evolution: Making Sense of Life, the textbook Doug Emlen and I have just published, is now evolving into a full-blown app for the iPad. Once you get the free app, you can download some of the book’s chapters. We’ve now got the first eight chapters in the iTunes store. Chapters 1 (the introduction) and Chapter 8 (natural selection in the wild) are available for free. Chapters 2-7 can be purchased individually for between $4.99 and $9.99. The full book will be available December 1st, 2012; all 18 chapters will be priced at $80.
For all the progress scientists have made in studying Neanderthals since then, the answer remains tough–in part because it’s not that easy to define a species.
NOVA asked me to write about this enduring question. You can read my answer here.
In 1988, Richard Lenski, an evolutionary biologist now at Michigan State University, launched the longest running experiment on natural selection. It started with a single microbe–E. coli–which Lenski used to seed twelve genetically identical lines of bacteria. He placed each line in a separate flask, which he provisioned with a scant supply of glucose. The bacteria ate up the sugar in a few hours. The next day, he took a droplet of microbial broth from each flask and let it tumble into a new one, complete with a fresh supply of food. The bacteria boomed again, then starved again, and then were transferred again to a new home. Lenski and his colleagues have repeated this procedure every day for the past 24 years, rearing over 55,000 generations of bacteria.
I first reported on Lenski’s experiment 12 years ago, and since then I’ve revisited it every few years. The bacteria have been evolving in all sorts of interesting ways, and Lenski has been able to reconstruct the history of that evolution in great detail, thanks to a frozen fossil record. Every 500 generations Lenski and his students sock away some bacteria from each flask in a freezer. They can thaw out these ancestors whenever they wish and compare them to their youngest descendants. Biotechnology has improved drastically since 1988, giving Lenski an increasingly powerful evolutionary microscope. When he started out, it could take months to identify just one of the many mutations that arose in each lineage. These days, he and his colleagues can sequence an entire E. coli genome for a few hundred dollars and find every single new mutation in its DNA.
Four years ago, I wrote here about one particularly fascinating episode in the evolution going on in Lenski’s lab. It started in 2003, when the scientists there noticed something odd in one of the 12 flasks. It had become much more cloudy than the others. In a microbiology lab, that’s a sure-fire sign that the bacteria in a flask have experienced a population explosion.
At first the team suspected that some other species of bacteria had slipped into the flask and was breeding quickly. But they found that the flask was packed with E. coli—descendants of the original ancestor that Lenski had used to start the entire experiment. Somehow the bacteria in this one flask had evolved a way to grow much faster than the other bacteria.
The scientists determined that the bacteria had made a drastic switch: from feeding on the glucose to another compound, called citrate. Citrate is an ingredient in the broth where Lenski’s E. coli grows. It’s not food; instead, it helps keep the minerals in the broth in the right balance for E. coli to grow.
To a microbiologist, the emergence of E. coli that can eat citrate in a lab is deeply weird. E. coli typically can’t feed on citrate in the presence of oxygen. Some strains of E. coli can draw in citrate, but only if there’s no oxygen around. To make the reaction work, they have to pump out another compound called succinate at the same time. The ability of E. coli to feed on citrate in the presence of oxygen is extremely rare; it occurs when E. coli picks up the necessary genes from other species. In its normal environment (inside us), natural selection must not favor these mutants. Scientists have been studying E. coli in labs for over a century, making it the most intensely studied species, on Earth (as I explain in my book Microcosm). But in all that time, there has been only a single report of a citrate-feeding E. coli in a lab, back in 1982.
The inability of E. coli to grow on citrate is so stark, in fact, that microbiologists use it as a way to tell whether bacteria they come across are E. coli or not. It was thus a surprise to Lenski and his students to find a flask of E. coli suddenly feeding on citrate. The bacteria had not picked up the genes from another species. Instead, their new ability must have evolved after Lenski started his experiment with a single E. coli. This was not simply a case of natural selection enabling a species to do something better. This was a case of doing something new.
Zachary Blount–then a graduate student in Lenski’s lab and now a post-doctoral researcher there–led the investigation into this strange new development. Blount and his colleagues took away the glucose and found that the E. coli could thrive on citrate alone. They then defrosted the bacteria’s ancestors and fed them citrate to figure out when they acquired the ability. They found that a tiny fraction of the bacteria around generation 31,000 were able to grow very slowly on the citrate. Over a couple thousand generations, they got better at growing on citrate–so good, eventually, that they took over the flask and turned it cloudy.
Blount and Lenski first reported the evolution of the citrate-eaters in 2008. Now, after another four years of painstaking research, they’re back with a new paper that details what happened down at the molecular level. It’s a fascinating look at how new traits evolve by duplicating and recycling old parts.
The scientists found that the evolution took place in three chapters. In the first chapter, the stage was set for the transformation. In the second chapter, the bacteria became citrate feeders. And in the third chapter, they became much better citrate feeders.
It usually makes sense to start a story with Chapter One. But in this case, it’s better to start with Chapter Two: The Birth of the Citrate Feeders.
When E. coli finds itself in the absence of oxygen, it switches on a gene called citT. Like other species (including us), E. coli turns genes on and off by attaching proteins to short stretches of DNA nearby. When E. coli senses a lack of oxygen, proteins clamp onto one of these genetic switches near citT. Once they turn the gene on, it produces proteins that gets delivered to the surface of the cell. There they poke one end out into the environment and pull in citrate, while also pumping out succinate. After the citrate gets inside the microbe, the bacteria can chop it up to harvest its energy.
When E. coli is growing in oxygen, however, no proteins land on the genetic switch near the citT gene, and so it remains silent. The microbe wastes no energy making a protein that won’t help it grow.
Evolution has rewritten this little algorithm in the citrate eaters. As one cell in Lenski’s flask divided, it duplicated its DNA with one fateful mistake. It accidentally copied the citT twice. The new copy ended up near a different genetic switch–a switch that turns on neighboring genes in the presence of oxygen, not the absence.
While citT remained silent in the other bacteria in the flask, in the mutant cell, it switched on. The microbe began sticking citrate transporters on its surface and started drawing in the molecule. This mutation must have occurred by generation 31,500, when Blount found the earliest citrate eaters. The mutation was a crude hack; it produced a microbe that could draw in a little citrate, but not a lot. It still had to feed on glucose to get by.
Thus endeth Chapter Two.
In Chapter Three, life got better for the feeble citrate eaters. They copied the citT gene, along with its oxygen-switch promoter. Now the bacteria could make even more CitT channels, and thus pull in even more citrate. The bacteria made a third copy, and could pull in even more. Blount and his co-authors proved that the extra copies helped the bacteria this way by defrosting bacteria from Chapter Two and inserting copies of citT into them. Those early citrate eaters immediately got much better at feeding.
The scientists also found other mutations that arose during Chapter Three. While they have yet to figure out what those mutations did, the evidence they’ve gathered so far suggests the mutations allowed the bacteria to break down citrate more efficiently so they could get more energy from their food.
The most intriguing part of the story, however, is the first– Chapter One: Setting the Stage.
When Lenski and Blount first began to study the citrate eaters, they wondered what would happen if they wound back the evolutionary tape and let the bacteria re-evolve. Would the citrate feeding evolve again?
Blount thawed out ancestors from various moments in the history of the bacteria and started putting them through the same evolutionary experiment again. In some trials, the bacteria did indeed evolve into citrate eaters–but only if they came from after generation 20,000. This discovery suggested only after 20,000 generations were the bacteria prepared to evolve into citrate eaters. They must have already acquired other mutations that set the stage.
To test this idea, Blount and his colleagues thawed out some of the “prepared” bacteria: late-generation E. coli that had not yet gained mutations to citT. They created a miniature ring of DNA loaded with many copies of CitT and the oxygen-sensitive switch, and inserted it into the prepared bacteria. As they predicted, the bacteria now could suddenly feast magnificently on citrate.
But if Blount and his colleagues inserted the DNA ring into the original ancestor of the line, it grew poorly on citrate. That failure suggested that the early-generation bacteria were not ready to receive this evolutionary gift.
And thus a history takes shape:
Chapter One (from generaton zeo to at least generation 20,000): Our hero, E. coli, picks up mutations that don’t seem to have anything to do with feeding on citrate. They might have helped the bacteria grow better on their stingy rations of glucose. At least one of those mutations set the stage for feeding on citrate.
Chapter Two (around generation 31,500): The bacteria accidentally rewire their genome, so that a new copy of citT switches on in the presence of oxygen. Thanks to the mutations of Chapter One, this rewiring yields a modest but important improvement. Now the bacteria can feed a little on citrate, as well as on glucose.
Chapter Three (from about generation 31,500 to 33,000–and beyond): The bacteria make extra copies of the new and improved citT. They can pull in more citrate; new mutations fine-tune their metabolism to grow quickly on the molecule. World domination soon follows.
It’s remarkable how this experiment contains many elements of evolution that scientists have noted in other species. It’s common for genes to get duplicated, and for the new copy to be rewired for a new job. Snake venom, to pick one example, also evolved when genes were accidentally copied and then rewired. A gene that originally produced a digestive enzyme in the pancreas, for instance, now started making that enzyme in a snake’s mouth. It turned out to be a crude but effective venom. Later mutations fine-tuned the new venom gene until it became wickedly good.
The only important difference is that it took millions of years for snakes to evolve their arsenal of venoms, and scientists can only reconstruct their evolution by comparing living species. But in the case of E. coli, the transition unfolded fast enough for someone to track it from start to finish–and restart it when necessary.
Reference: Blount et al, “Genomic analysis of a key innovation in an experimental Escherichia coli population.” Nature, September 19 2012.
Two years ago, I wrote in the New York Times about scientists exploring evolution to discover the function of our genes. We share a 1.2 billion-year-old common ancestor with fungi, for example, and it turns out that fungi (yeast in particular) have networks of genes remarkably similar to our own.
Back in 2010, the scientists I interviewed told me they hoped to use this method to find new drugs. In today’s New York Times, I write about how they’ve delivered on that promise. It turns out that a drug that doctors have used for over 40 years to kill fungi can slow the growth of tumors. It’s a striking illustration of how evolution provides a map that allows medical research to find their way to promising new treatments. Check it out.
The world, it bears reminding, is far more complicated than what we can see. We take a walk in the woods and stop by a rotting log. It is decorated with mushrooms, and we faintly recall that fungus breaks down trees after they die. That’s true as far as it goes. But the truth goes much further. These days scientists do not have to rely on their eyes alone to observe the fungus on a log. They can drill into the wood, put the sawdust in a plastic bag, go to a lab, and fish the DNA out of the wood. A group of scientists did just this in Sweden recently, sequencing DNA from 38 logs in total. They published their results this week in the journal Molecular Ecology. In a single log, they found up to 398 species of fungi. Only a few species of fungi were living in all 38 logs; many species were limited to just one.
Consider that on your next walk in the woods. The one or two types of mushrooms you see on a log are an extroverted minority. The log is also filled with hundreds of other species that don’t make themselves known to you. Their invisible exuberance is a paradox. The fungi that live on rotting logs all make a living by releasing enzymes that break down wood. It’s puzzling that so many species can coexist in a log this way, instead of a single superior fungus.
The forces that drive up the diversity of fungi in a log are similar to the ones that fosterer the thousands of species of microbes in our bodies. For one thing, a log or a human body is not a uniform block of tissue. They both have geography. A microbe adapted to the acid bath of our stomach won’t fare well on the harsh desert of the skin. Likewise, what it takes to succeed as a fungus in a branch is different from what it takes in the heartwood of the trunk.
The human body changes over time, and a rotting log does, too. Babies are colonized by pioneer microbes, which alter the chemistry of their host and make it more welcoming to late-arriving species. The pioneers on a fallen log may include the spores of some species of fungi lurking in trees while they’re still alive. They burst into activity as soon as the tree crashes to the forest floor. Other species, delivered by the wind or snaking up through the soil, find it easier to infiltrate a log that’s already starting to rot. The early fungi may go after the easy sugar in the log, while later species unlock the energy in tougher tissues, like lignin and cellulose. Which particular pioneer starts to feed on a log first can make it inviting to certain species but not others.
Warfare also fosters diversity in a log. The fungi inside a log battle each other for food, spraying out chemicals that kill off their rivals. Each species has to balance the energy it puts into making enzymes to feed and weapons for war. Sometimes the war ends in victory for one species, but very often the result is a deadlock that leaves several species in an uneasy coexistence. There are more peaceful forces at work in a log, too. Many species of fungi in a log depend on each other. One species may feed on the waste produced by another, and supply another species with food in turn.
The world in a log influences the world as a whole. If it wasn’t for wood-rotting fungi, forests would be strewn with the durable remains of dead trees. When the first massive forests spread over the land 350 million years ago, fungi hadn’t yet adapted to decomposing logs. Instead of turning to soil, many trees ended up as coal. The great age of coal ended about 300 million years ago–right around the time that tree-rotting fungi emerged. Their emergence may have brought the age of coal to an end.
Three hundred million years later, that coal is coming back up to the surface of Earth to be burned. Some scientists are investigating fuels that could replace climate-warming ones like coal. One possibility is to pull out the energy-rich sugar locked up in the lignin and cellulose of crop wastes or switchgrass. On our own, we would not be able to perform the necessary alchemy. But fungi know how, and so scientists are sequencing the genomes of wood-rotting fungi to borrow their tricks. This is big-scale science: the genomes of over a dozen species have been sequenced or are in the sequencing pipeline. Yet a single log may contain twenty times more fungus genomes. At the moment, we can say for sure that the few mushrooms we see on a rotting log are far from its full reality. But it will be a long time before we know how all the parts of that reality fit together.
Next month, my first co-authored book is coming out. Evolution: Making Sense of Life is a textbook for biology majors, and my co-author is Doug Emlen, a professor at the University of Montana. I’ve heard many tales of disastrous collaborations between scientists and science writers, and so I don’t enter into them lightly. But working with Emlen has been a delight. No matter how many times we’ve had to rewrite a chapter, he threw himself into the work as if he was cannonballing into a swimming pool. And yet somehow Emlen was advancing his own research in evolutionary biology at the same time, quietly chugging away on some remarkable experiments. And today–just a week after we shipped our book off to the printers–Emlen’s latest, most intriguing paper has just come out in the journal Science.
If he wasn’t my co-author, I’d probably be writing about the new paper in the New York Times (or perhaps get into a bare-knuckle fight with the other reporters there for the right to do so). But given our connection, I’m going to use my blog to describe it.
When you’re a young evolutionary biologist, you’ve got to find creatures and questions that will sustain your career. Twenty years ago, Emlen realized that the perfect creatures for him would be horned beetles. In thousands of beetle species, the males grow enormous horns, which they use to battle each other for territories–be they tunnels, branches, or globs of sap. Often, male beetles will size each other up and not even bother challenging a beetle with a giant horn–because horns are a reliable signal of the good shape of a male beetle. These beetles embody Darwin’s original ideas about how sex could shape life. The competition for mates would favor mutations that enlarged the horn–not because it boosted the survival of beetles, but because it made male beetles more successful in the struggle for the chance to mate. (Terri Gross spoke to Emlen about beetles, and animal weapons in general, on Fresh Air.)
But there’s another way to contemplate a beetle’s horn. It develops as a beetle undergoes its metamorphosis from a larva into an adult. The mutations that build bigger horns must do so by altering the course of development. Until the late 1900s, the evolution of animal development was fairly mysterious, because scientists had no idea of which genes were involved in building emryos. But these days, that’s changed drastically. Emlen and I write about this at length in Evolution: Making Sense of Life, and online you can read about this field–”evo-devo”–over at the Understanding Evolution web site.
Emlen and his colleagues have discovered all sorts of intriguing things about the development of beetle horns. For example, big horns pull away precious resources from other parts of the developing beetle body. Male beetles with big horns have small eyes and antenna, Emlen has shown. This trade-off may put a limit on how big horns can get, since males with reduced eyes and other senses won’t fare well, even if they can battle any rival.
Beetles are hardly the only animals with sexual ornaments. Male widowbirds have long feathers, elk have huge antlers, and fiddler crabs have massive claws. One question that has occupied evolutionary biologists for decades is why these ornaments tend to be such reliable signals. If all it takes to scare off a rival beetle is a big horn, then it would make sense for weak beetles to shore up all their resources and build massive ornaments. Yet big ornaments continue to serve as trustworthy signals–as a warning to rival males and as an attraction for females.
In his new study, Emlen and his colleagues offer an evo-devo explanation for the link. As animals grow, two proteins play a major role: insulin and insulin-like growth factor (known as IGF). These hormones flow through the body, latch onto special receptors on cells, and trigger a series of chemical reactions that lead animals to grow faster. The amount of these proteins coursing through the body depends, in turn, on external factors such as how good the animal’s diet is. High insulin/IGF levels will spur an animal to develop a large body; in bad conditions, its body will be small. But individual animals vary in this response: in a good environment, the signals that some animals get from their insulin/IGF proteins make them grow bigger than other animals.
Emlen and his colleagues wondered if sexual ornaments were especially sensitive to the insulin/IGF signals. To find out, they turned to the aptly named rhinoceros beetles. The scientists injected molecules that blocked the insulin/IGF signal into rhinoceros beetle larvae just before they started to grow their horns.
Blocking the signal modestly stunted the bodies of the beetles. But it devastated the horns. Compared to the wings of the beetles, Emlen and his colleagues found, the horns were eight times more sensitive to manipulations of the insulin/IGF signals. (In this photo, the beetle on the right side has been injected with the insulin/IGF blocking molecules.)
The new study suggests that the exaggerated size of the beetle horns is unavoidably linked to the overall quality of a male. It grows in response to the same signals that control the entire body, but is more sensitive to them. There’s no way for weak males to cheat, because they can’t avoid using insulin/IGF signals to build a horn. If they have weak signals, they’ll produce a small horn.
And what goes for beetles may go for some other animals–or maybe a lot of other animals. When red deer stags grow new antlers, for example, the cells at the tips produce receptors for insulin/IGF. Emlen doesn’t touch on humans in the new paper, but the fact is that insulin/IGF signals are crucial in the transformation of boys to men, complete with big bones and muscles. Whether there’s a link in our species as there is in beetles is something I hope that we can report on in future editions of our book.
[Images: Doug Emlen]
[Note: This is the last of a four-part series:
For the past five days, I’ve been trying to get an answer from creationists. Today, I finally got it. And it’s an instructive lesson in how creationism makes itself irrelevant to the progress of science. Plus, it’s a good opportunity to look at the delightfully sloppy way our chromosomes evolve.
I’ve been blogging this experience along the way, so I won’t go back over it all again. Consider this the final chapter in a strange saga.
I do have to recap a little, though, so that this post makes sense.
As I blogged on Thursday, there’s a growing pile of evidence for how one of our chromosomes (chromosome 2) evolved through a fusion of two other chromosomes. I focused in particular on a paper that came out in the journal Genome Research last month from Evan Eichler at the University of Washington and his colleagues. Among many other pieces of evidence are telomeres, bunches of repeating DNA that typically form caps at the ends of chromosomes. There is telomeric DNA right in the middle of chromosome two.
On July 6, a site that promotes intelligent design (a k a the progeny of creationism) published an article by David Klinghoffer, the site’s editor, questioning whether this actually happened. Klinghoffer stated that the telomeric DNA at the fusion site “appears in a ‘degenerate,’ ‘highly diverged’ form that should not be the case if the joining happened in the recent past, circa 6 million years ago, as the Darwinian interpretation holds.”
This passage stuck out for several reasons. Who was he quoting? Why was he calling six million years ago the recent past? Who ever said that if the fusion happened six million years ago, the DNA there should not be degenerate or diverged?
Unable to ask Klinghoffer directly at his site (no comments allowed), I did the next best thing and wrote my question on a Facebook page that’s also linked to the same outfit, and which posted his article. What, I asked, was the evidence for this particular claim?
I was told to read a book that expresses doubts about human evolution. I asked for scientific papers. I got silence, invitations to debate, and more distraction.
After five days of repeatedly asking my question–and of being accused of lies, misdemeanors, and being some kind of duck–I discovered this morning that Klinghoffer has at last provided the evidence for his claim.
Did he direct me to a passage from Eichler’s new 2012 paper?
Did he point me to some other recent paper, such as the one unveiling the chimpanzee genome in 2005, which also provided additional evidence of chromosome fusion?
Instead, he typed out a few paragraphs from the book in question, Science and Human Origins, recently published by the Discovery Institute Press, and written by three Discovery Institute-related people, Douglas Axe, Ann Gauger, and Casey Luskin. (Although the book is written by three people, Klinghoffer only refers to Luskin having written the fusion stuff. I have no idea why. Luskin himself has done no research on chromosomes, and is not a scientist.)
Here’s what it’s taken so long for Klinghoffer to divulge:
I repeat my contention that reasoned discussion of a book isn’t possible unless you grapple with the argument the book makes, as opposed to obsessively flogging one small point because you figure you may have an advantage there. Zimmer simply will not consider the larger case for skepticism about evolutionary explanations of human origins. He’ll only lecture us about human chromosome 2.
It would seem to be reasonable at this point to give up on Carl Zimmer. For readers who want to know what Casey said in his chapter, and what I had in mind when I wrote my own post, here are several paragraphs I highlighted in my copy of SHO [Science and Human Origins-cz]:
…[T]he evidence for chromosomal fusion isn’t nearly as clear-cut as evolutionists like [Kenneth] Miller claim.
Telomeric DNA at the ends of our chromosomes normally consists of thousands of repeats of the 6-base-pair sequence TTAGGG. But the alleged fusion point in human chromosome 2 contains far less telomeric DNA than it should if two chromosome were fused end-to-end: As evolutionary biologist Daniel Fairbanks admits, the location only has 158 repeats, and only “44 are perfect copies” of the sequence.46
Additionally, a paper in Genome Research found that the alleged telomeric sequences we do have are “degenerated significantly” and “highly diverged from the prototypic telomeric repeats.” The paper is surprised at this finding, because the fusion event supposedly happened recently — much too recent for such dramatic divergence of sequence. Thus the paper asks: “If the fusion occurred within the telomeric repeat arrays less than ∼6 mya [million years ago], why are the arrays at the fusion site so degenerate?”47 The conclusion is this: If two chromosomes were fused end-to-end in humans, then a huge amount of alleged telomeric DNA is missing or garbled.
Finally, the presence of telomeric DNA within a mammalian chromosome isn’t highly unusual, and does not necessarily indicate some ancient point of fusion of two chromosomes. Evolutionary biologist Richard Sternberg points out that interstitial telomeric sequences (ITSs) are commonly found throughout mammalian genomes, but the telomeric sequences within human chromosome 2 are cherry-picked by evolutionists and cited as evidence for a fusion event….
To explain why this is such a massive evidence fail, I need to talk a bit about telomeres.
The ends of chromosomes are very vulnerable places. If they simply dangle loosely, DNA-cutting enzymes can nibble away at them, destroying the genes they encounter. The dangling end of one chromosome can also get attached to the dangling end of another, fusing chromosomes together. We are mostly protected from such changes thanks to special proteins called telomerases. They tack on little repeating bits of DNA, which form a loop–a telomere–so that chromosomes end as a hairpin curve, rather than dangling ends.
When cells divide, however, telomeres tend to get chewed up. To keep telomeres big enough to protect their chromosomes, telomerases keep adding more DNA to them. In a 1997 paper, Nobel-prize-winning biologist Carol Greider and her colleagues illustrated just how important this addition is by creating mutant mice that couldn’t produce telomerase–and could therefore not add extra DNA to their telomeres.
The mice were healthy enough to grow up and have babies. But from one generation to the next, their telomeres got shorter until they disappeared. After just four generations, the mice suffered an explosion of chromosome fusion. Their dangling DNA then began to get chewed away, damaging their genes until they became sterile.
This experiment and other studies indicate that defective telomeres with few repeats are vulnerable to chromosome fusion. So it would be no surprise to find that a fusion between two chromosome had a low number of repeating bits of DNA.
And once the chromosomes did fuse, the telomeres would now be stuck in the middle of the chromosomes, where telomerases would not be adding any extra DNA. You’d expect that over time, bits of the telomeres would get deleted and not replaced.
So the small quantity of telomere DNA does not, in fact, raise grievous doubts about the evolution of fused chromosomes. Nor does the fact that the repeating DNA in the fused chromsome has mutations in it. Telomere DNA is just prone to mutation. In fact, if you look at the telomere on a chromosome, you’ll typically find that the newest pieces of repeating DNA are correct, but the older segments further from the loop’s end are slightly garbled. These errors arise in your own body. If a chromosome’s telomeres are damaged, you might well expect the new ones to be gone, and the garbled ones remain.
You’d also expect that after the chromosomes fused, the telomere DNA would continue to mutate. Which brings us to Daniel Fairbanks, the geneticist quoted by Luskin and Klinghoffer. Quoted isn’t the right word: cherry-picked is. They select just four words out of a sentence, so as to distort Fairbanks’s words.
You can see for yourself. Luskin quotes Fairbanks from Relics of Eden, a very good popular book in which Fairbanks outlines the genetic evidence of human evolution. Here’s the page in Google Books where the quote comes from. Fairbanks is talking about the chromsome fusion. I’m going to quote the passage in full, italicizing the cherry-picked bit that Klinghoffer and Luskin pulled out.
Of the 158 repeats, 44 are perfect copies of TTAGG or CCTAA. In most cases, the remaining repeats differ from the standard sequence by no more than one or two base pairs.
This is precisely what we expect if the fusion happened long ago in the remote ancestry of humans. After the fusion event, the repeats no longer functioned as telomeres, so mutations (changes in the DNA sequence) in them had no harmful or beneficial effect. The ancient telomere at the fusion site is now a nonfunctioning relic of evolution embedded in the middle of the chromosome. The more generations humans are separated from the fusion event, the more mutations we expect to accumulate in the sequence. Because the majority of the repeated segments have mutations in them, the chromosomes must have fused a long time ago, probably tens of thousands of generations deep into our ancestry. Thus, the evidence clearly eliminates chromosome fission and independent origins as reasonable alternatives to fusion.
To push the idea that this telomere DNA is way too divergent to have evolved through fusion, Luskin quotes from this 2002 paper, which you can read for free. This research was carried out back before scientists had the chimpanzee genome at hand, and when the human genome was still only roughly mapped out. (Repeating chunks of DNA are particularly tough to sequence and map to their location in the human genome.)
Barbara Trask of the Fred Hutchinson Cancer Research Center and her colleagues had to do the best they could, sequencing the region around the fusion site in humans and around chimpanzees. They found that all of the chunks around the fusion site in human chromosome two mapped to corresponding parts at the ends of two chimpanzee chromosomes. Again–this is exactly what you’d expect if fusion occurred in our distant ancestors. “When observed at the sequence level, the ancestral chromosomes appear to have undergone a straightforward fusion,” Trask and her co-authors write. (Funny that this is not the quote that Luskin or Klinghoffer choose to pull out.)
Subsequent research has supported this conclusion. Eichler’s 2012 paper, for example, shows how the genes across the entire fused chromosome still retain much of their original order in their unfused predecessors. See my post for pictures that illustrate this.
Again, Luskin doesn’t even try to address the large-scale similarity of these chromosomes.
One particularly neat piece of evidence for fusion has to do with the centers of chromosomes, called centromeres. Centromeres have a distinctive structure, and they play a crucial part in the replication of chromosomes. If human chromosome two had indeed evolved from the fusion of two older chromosomes, then it must have acquired two centromeres. As Trask and her colleagues note in their 2002 paper, human chromosome two does, indeed, have two centromeres. One is still working, while the other has been inactivated by mutations.
But you’d never know about this evidence from the Discovery Institute.
Being good scientists, however, Trask and her colleagues pointed out some intriguing results in their 2002 study. For example, the repeating DNA they sequence is very divergent. This is the sentence that Luskin quotes. But he then fails to mention the explanations that Trask and her colleagues start to consider in the very next sentence. By 2002, for example, scientists already knew that telomere DNA has a high mutation rate. And in 2005, when Trask got a chance to compare the human and chimpanzee genomes, she confirmed that, indeed, telomeres and nearby DNA undergo lots of mutations. In other words, you’d expect this kind of DNA to be divergent and degenerate.
The third piece of evidence Klinghoffer and Luskin offer comes, unquoted, from Richard Sternberg. There’s no footnote, so this is presumably just Sternberg telling Luskin this information. Sternberg, incidentally, is a fellow at the Discovery Institute–something Luskin fails to note. Sternberg claims that there’s telomere DNA in the middle of lots of mammal DNA, and so scientists must be cherry-picking the stuff in chromosome two to indoctrinate people about evolution.
As I hope is now clear, there is an overwhelming amount of evidence that the telomere DNA in the middle of chromosome 2 is the result of fusion–evidence both from the fusion site, and across the entire chromosome. So this is the opposite of cherry-picking. It is true that there are hundreds of chunks of telomere DNA wedge in mammal chromosomes. But this fact in no way undermines the evidence for the fusion of human chromosome two.
To see why, check out this 2008 paper, “Telomeric repeats far from the ends: mechanisms of origin and role in evolution,” which three Italian scientists published in the journal Cytogenetic and Genome Research. These scientists carefully examine telomeric repeats located in the interior of chromosomes in a number of mammal species. Lo and behold, they found evidence that these chunks of telomere DNA got moved from the ends of chromosomes to their interior, too. Their research shows that there are a number of ways that this has happened. Some of these moves started with a chromosome fusion. Later, these chromosomes broke, and one of the resulting chunks got swapped with a chunk of another chromosome. As a result, the telomere DNA was able to spread far from the ends of chromosomes.
Another opportunity to spread telomere DNA occurs when DNA breaks. To fix broken DNA, specialized proteins zoom in to stitch the loose ends back together. But these proteins can also grab onto the telomeres at the end of chromosomes. Thanks to this glitch in the repair system, cells will sometimes accidentally insert a bit of telomere DNA at a spot where they’re trying to repair a break. The Italian researchers support this hypothesis with comparisons of mammal genomes, which reveal the footprints of these events.
In other words, the presence of other pieces of telomere DNA away from the ends of chromosomes does not bring the fusion of chromosome two into question. Instead, they arose through other fusions and other mutations. In other words, more evolution.
And that’s it.
After five days of stonewalling and name-calling, Klinghoffer points us to a passage from a book published by his employer, the Discovery Institute, written by someone else at the Discovery Institute. The passage he points us to cherry-picks another book and a 2002 paper. Reading the original sources quickly reveals that Luskin’s interpretation of those quotes is wrong. Luskin also nods to another Discovery Institute fellow, who makes a comment that is clearly contradicted by peer-reviewed research. Luskin has nothing to say about any of the research that has come out in the past ten years. Klinghoffer has nothing to say, either.
For Klinghoffer to say that you have to read the entire book to appreciate the weight of the evidence about human chromosome two is absurd. Klinghoffer himself made a specific claim, and the evidence he offers actually shows that he’s wrong. Unless the rest of the book provides better evidence concerning human chromosome two, it’s irrelevant to my question.
And if the rest of the book is as wrong as this passage, then I hardly see why it’s worth reading.
And that is why I ask for evidence.
[Update: Fixed Fairbanks's first name. Daniel, not Douglas. Must be a swashbuckling oversight!]
[Note: This is the third of a four-part series
On Wednesday, I asked creationists for evidence. Over the past four days, I’ve been ordered to buy their book, offered it for free, invited to a debate and to guest blog. I’ve also been accused of lies and misdemeanors, of harrassing innocent creationists, and of being a duck. Actually, a hounding duck. But I still haven’t gotten my answer.
There is, of course, a lesson here.
Briefly, here’s the background. (For more details, read this post I wrote Thursday.) The Discovery Institute promotes intelligent design, which a Federal judge has declared “the progeny of creationism.” They have a staff, along with fellows, who write books (many of which are published by the Discovery Institute Press), run web sites, appear on cable TV, all to attack evolutionary biology and promote intelligent design. Their ranks include a few scientists (ie, people with Ph.D.’s who’ve published research in peer-viewed scientific journals), but in none of their published papers, to my knowledge, do they say anything like, “Our experiment thus provides clear evidence of intelligent design.” Instead, they make their big claims about intelligent design in their non-peer reviewed books and on their web sites. In 2005, the Discovery Institute set up an outfit called the Biologic Institute, where some scientists are supposedly doing the research that will show the world that Intelligent Design is the real deal. So far, they haven’t published any scientific papers in peer-reviewed journals to that effect.
On Wednesday, David Klinghoffer, the editor-in-chief of one of their sites, Evolution News and Views, published a piece promoting a new book from the Discovery Institute Press about human evolution, co-authored by two people from the Biologic Institute and one from the Discovery Institute. It was called, “A Veil Is Drawn Over Our Origin As Human Beings.” Along the way, Klinghoffer raised the issue of our fused chromosome, which, as I wrote Thursday, preserves clues to its origin as two separate chromosomes long ago. Klinghoffer claimed that the structure was not what you’d expect if the chromosome had fused six million years ago.
So here we have a claim. Scientific claims are based on evidence, or at least they should be. I wanted to know what the evidence was for this particular claim, but I couldn’t ask on Evolution News & Views (no comments allowed). So I went over to Facebook. There, the Biologic Institute has set up a page where they posted links to other web pages, one to including Klinghoffer’s page. And on Facebook, you have to let people comment. The biologist Nick Matzke was using the comments to set them straight with various lines of evidence about human evolution, which prompted the Biologic Institute to lay down a 100-word-or-less rule for comments. So I jumped in to ask–briefly–for the evidence about the claim about the human chromosome.
Whoever runs the Biologic Institute’s page responded by telling me to buy their new book. After all, as a book author myself, I wouldn’t just deliver the contents of my book to anyone who asked on my blog, would I?
Well, no, I replied. I then asked again, this time only requesting a citation to a paper that backed up their claim about the fused chromosome.
Now the Biologic Institute stopped replying. Other people left comments to let me know that they had read the book, and that the cited evidence amounted to nothing but a cherry-picked sentence from a ten-year-old paper. (Some of these comments have since been deleted.)
I asked the Biologic Institute if this account was true. Again, no answer.
Instead, I got an email from Klinghoffer himself. Rather than answer my question, he invited me to write a couple thousand-word pieces on Evolution News and Views as a debate with an unnamed co-authors. The debate would be on the various issues in the book. (Klinghoffer added that he wanted a debated focused on “ideas, not personalities.” This civility-minded person is the same guy who once wrote that one my blog posts was “preening and self-congratulatory.”) I hadn’t asked for such a debate, so I said no.
Instead, I asked again for the evidence. No answer.
Klinghoffer responded instead by publishing a piece on Evolution News and Views entitled, “We Called Out Darwinian Critic Carl Zimmer and He Folded.” Instead of answering my question, he condemned me for not reading the Discovery Institute’s book. “So you see what we’re up against,” he moaned. “Carl hasn’t read the book and now, having ducked out of a proper debate, he can go on denouncing it without ever having read it. He’s perfectly willing to waste our time on Facebook, where the phrase ‘pecked to death by ducks’ comes to mind.”
When the Biologic Institute posted a link to the piece on Facebook, I asked them again for an answer. No reply.
But David “Ideas Not Personalities” Klinghoffer was not through with me. The next day he returned to his comment-free platform to accuse me of “hounding our Biologic Institute colleagues on their Facebook page about a particular pet subject that he thinks he knows something about–chromosomal fusion at human chromosome two.”
Klinghoffer then got on Facebook to add a link to this piece on the Biologic Institute page. So I asked him my question again there. What is the evidence for the claim he made?
Again, nothing. By this point I had lost count of how many times I had asked the question.
Meanwhile, I put together this post to explain the latest research on the evolution of our fused chromosomes, from the world’s experts on primate genomes. By comparing the genomes of humans, chimpanzees, and gorillas, they could reconstruct what the original chromosomes were like, and how they evolved in each lineage–thanks to the kinds of mutations that scientists can see today in humans, as well as in many other species.
Unlike Klinghoffer, I let people comment on my posts. As of this writing, there are 70. A fair number of them claimed that intelligent design was the best explanation for our chromosomes. On Saturday, one of these commenters scoffed at the idea that mutations and evolutionary mechanisms could bring it about. If even just two mutations were required, I was out of luck.
Two? Again, I asked for the evidence. And this time I got an answer. I was directed to this 2008 paper in Genetics.
And this is why I ask for evidence. Because I can go do some research to see if the evidence holds up. The paper is a model, informed by experiments, of the rate at which mutations arise. It inspired another Discovery Institute fellow to claim it was evidence that evolution was too slow to have produced enough mutations in six million years to give rise to humans. And then the authors of the paper themselves wrote a letter to make it explicitly clear that the Discovery Institute was wrong. (Here’s a more recent paper that shows that the wait for mutations is not long, courtesy of another comment.)
On Saturday, I got another email from an Intelligent Design web site. This one is called Uncommon Descent. “We sponsor guest posts from people who disagre with us but are civil and well-informed on the issues,” wrote Denyse O’Leary. Would I want to write one?
I replied by pointing out that writing a guest blog post would be a redundant waste of time, since I had already asked my question many times over, and Uncommon Descent had actually just linked to my own blog post. I also found it strange that O’Leary would politely describe me as “civil and well-informed” in a message to me, when she had just written on Uncommon Descent that I am the sort of “Darwinist” who “only needs to pretend to know what they are talking about.”
Well, that little burst of politeness was fleeting indeed. Today, Uncommon Descent featured a new piece about me: “Carl Zimmer Doubles Down on Chromosome Two Lifes and Misdemeanors.”
Today’s attack comes from Discovery Institute fellow Cornelius Hunter. Hunter got a Ph.D. in biophysics at the University of Illinois, where he published three papers on protein structure a decade ago according to PubMed. Now he’s an adjunct professor at Biola University, an evangelical university in California.
Hunter claims that the evidence for a chromosome fusion in our ancestors only makes sense if we have already bought into the theory of evolution. It’s a long post that only gets around to what’s happened to the chromosomes at the very end.
The site of the fusion event on human chromosome number two does not provide an obvious picture of a past fusion event. There certainly are suggestions of such an event, but it is far from obvious as evolutionists claim.
Furthermore such an event, if it could survive, would have to take over the pre human population. In other words, the existing 48 chromosome population would have to die off. This is certainly not impossible, but there is no obvious reason why that would occur.
There are problems with the evidence. Perhaps the fusion event occurred, but the evidence carries nowhere near the certainty that evolutionists insist it does…
If evolution is not taken as an a priori, then these evidences are far less compelling. From this theory-neutral perspective, what is important is not reconciling chromosome counts or chimp-human chromosome similarities (after all, those are found throughout the respective genomes). What is important is the more direct evidence of a fusion event, such as in the region where the two chromosomes would fuse, and other tell-tale signs in the chromosome two.
Here the evidence is mixed. Certainly it is far less compelling than evolutionists ever tell their audiences. This need not be controversial. But it is.
That’s it. It’s not obvious. The evidence is mixed. How is it mixed? Hunter never says. What would be obvious evidence to him? He never says. What does he make of the latest research supporting the evolution of the fused chromosome? We have no idea. And–to sing the old refrain–what is the evidence for Klinghoffer’s claim? Hunter never says.
That’s where our story now stands. I’ll end this post the way this whole adventure began, with the question that has gone unanswered in so many, many ways:
An article on Evolution News & Views stated that the evidence for the fusion of human chromosome two “appears in a ‘degenerate,’ ‘highly diverged’ form that should not be the case if the joining happened in the recent past, circa 6 million years ago, as the Darwinian interpretation holds.” Where is the scientific evidence for this?