00:00:04One question: "Why is there such a stunning diversity of life?"One answer: Evolution.
00:00:12One answer: "Evolution: Charles Darwin's brilliant theory that explains how species adapt and change." It's been called the best idea anyone ever had.
00:00:16But there's one big problem: How does it actually work?
00:00:25Now, extraordinary science is answering that question.
00:00:31It is uncovering the hidden mechanisms inside creatures' bodies that can explain astonishing transformations, like how birds can evolve from dinosaurs...
00:00:44why a fish was once your ancestor...
00:00:48and above all, what makes us human.
00:00:54Right now onNOVA, you'll find out what Darwin never knew.
00:01:13Major funding forNOVA with captioning is provided by the following: STEPHEN GREENLEE: Natural gas is a cleaner-burning fuel, yet a lot of natural gas has impurities like CO2 in it.
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00:02:54NARRATOR:The Tree of Life on earth is one of stunning diversity.
00:03:099.000 species of birds.
00:03:15350,000 kinds of beetles.
00:03:2228,000 types of fish.
00:03:28Two million living species and counting.
00:03:35And we are just one of them.
00:03:44(birds calling) But why is there such an amazing variety of animals?
00:03:59Why are there so many types of fish?
00:04:04So many different species of beetle?
00:04:08How did this extraordinary profusion of life on earth come about?
00:04:14Today, we celebrate the man who would ultimately answer that question.
00:04:22Charles Darwin.
00:04:26He was born 200 years ago and it is 150 years since he published the work that has become the bedrock of our understanding of life on earth.
00:04:38CLIFF TABIN: What Darwin wanted to understand was how you get this extraordinary diversity of life on earth.
00:04:44He was spot on.
00:04:46He really nailed it.
00:04:49NARRATOR: Darwin's theory of evolution-- his account of why species adapt and change-- has been called the best idea anyone ever had.
00:04:59But even Darwin admitted that his work was incomplete.
00:05:05Vast questions were still unanswered.
00:05:08And the biggest question was: How?
00:05:11How did evolution take place?
00:05:12SEAN CARROLL: He didn't know any of the mechanics of that process.
00:05:18He didn't understandthe physical forces that would actually changethe way species appeared.
00:05:26NARRATOR: But today, we can answer the questions that Darwin could not.
00:05:39We can look under the hood of evolution and see exactly how this mysterious process gives rise to such astounding diversity.
00:05:48TABIN: What's incredible about this time from a scientific perspective is, we're going to be ableto understand that diversity.
00:05:56And that just addsto the excitement.
00:05:58It doesn't demystify it.
00:06:00It makes it all the more magical.
00:06:03NARRATOR: And this is the magic and mystery of evolution.
00:06:07Over eons of time, a single species gives rise to many.
00:06:12An ancient fish evolves to become the ancestor of all four-limbed animals, even us.
00:06:20And one species, our own, develops a large and uniquely complex brain, enabling us to dominate the planet.
00:06:30This is the search for the answers to what Darwin never knew.
00:06:40(children chattering) Darwin began his love affair with nature when he was a child, just like many of his modern followers, including evolutionary biologist, Sean Carroll.
00:06:55CARROLL: I developed my interest in animals the same way I think most biologists did, which was either going out in the backyard or going to zoos.
00:07:03And anytime I got a chance, I'd flip over logs and look for salamanders and snakes and frogs and things like this.
00:07:10And I was just fascinated with their patterns and behavior.
00:07:13NARRATOR: So it was with the young Charles Darwin.
00:07:17CARROLL: Young Charles liked to traipse around the outdoors.
00:07:21He loved to collect beetles and things.
00:07:22He was a completely ordinary kid.
00:07:24And he didn't like school.
00:07:27In fact, he was such a poor student that his father, a rather successful physician and a pretty imposing figure, was worried about Darwin's direction in life.
00:07:37NARRATOR: So his father packed him off to Edinburgh, the finest medical school in Europe, to become a doctor.
00:07:50But young Charles was just too squeamish.
00:07:55CARROLL: And he was really horrified by medical school.
00:07:57He witnessed an operation on a child and this is in the era before anesthetics.
00:08:01And he just fled the operating theater vowing never to return.
00:08:13NARRATOR: Next, his father sent him to Cambridge to study for the clergy.
00:08:21He didn't succeed at that either, but he did find his direction in life, reviving his childhood interest in nature.
00:08:28CARROLL: Darwin starts on his path to his divinity degree and he starts to mature as a student.
00:08:36He becomes more serious about some subjects, particularly natural history, and he learns a lot more about botany and about geology and these things.
00:08:43He's becoming a pretty solid field scientist.
00:08:46NARRATOR: His reputation as a naturalist gained him a spectacular invitation.
00:08:52CARROLL: Charles was offered a place on the British Navy ship theHMS Beagle, whose mission was to survey the waters around South America.
00:09:03Now, the captain of theBeagle wanted a well-educated, scientific person aboard, and a dinner companion, somebody to share conversation with.
00:09:11And Darwin fit the bill perfectly.
00:09:21NARRATOR: And so, Charles Darwin set off on a fateful voyage that would revolutionize our understanding of life's great diversity.
00:09:35The voyage of theBeagle took nearly five years.
00:09:38It wove its way from the Cape Verde islands and along the coast of Brazil.
00:09:45It was in Argentina that he made his first important discovery.
00:09:51CARROLL: Early on in the voyage, Darwin found some amazing fossils.
00:09:54He dug up some skulls, some jaws, some backbones of what turned out to be giant mammals.
00:10:01Now, these were clearly extinct and Darwin began to ponder, what was the relationship of those fossils to the living animals of South America.
00:10:18NARRATOR: But one port of call on Darwin's voyage proved more important than all the others.
00:10:28The Galapagos.
00:10:31This cluster of 13 isolated islands lies 600 miles off the coast of Ecuador in the Pacific Ocean.
00:10:38These islands are home to unusual animals found nowhere else on earth.
00:10:47Penguins that live at the equator and swim in warm water, instead of the frigid seas of the South Pole.
00:10:56Giant tortoises that weigh up to 600 pounds.
00:11:01Iguanas, huge lizards that swim and dive in the sea.
00:11:07Everywhere else, they dwell only on land.
00:11:13(barking) Traveling for the first timein the Galapagos, Sean Carroll is seeingthe same creatures that so intrigued Darwin.
00:11:24CARROLL: Of all animals, I think these marine iguanas are the greatest symbol of the Galapagos, what I most wanted to see here.
00:11:30And to see them in their native habitat, blending against that black rock, just as Darwin described it...
00:11:35It's an absolute thrill.
00:11:39DARWIN (dramatized): It's a hideous looking creature, of a dirty black color, stupid and sluggish in its movements.
00:11:49They're as black as the porous rocks over which they crawl.
00:11:55NARRATOR: Darwin meticulously described the iguanas in his diary.
00:12:01But he was far from the scientific authority he would become.
00:12:06CARROLL: The Darwin that arrived here was not the great theorist that we know today.
00:12:11He was a 26-year-old collector, collecting really, almost at random, any kind of plants, any kind of animals, any kinds of rocks.
00:12:18He didn't even know the meaning of what he was collecting until much later.
00:12:23NARRATOR: He was also fascinated by the giant tortoises, which allowed him to ride on their backs as they slowly lumbered around.
00:12:32DARWIN: I frequently got on their backs and then, upon giving a few raps on the hinder part of the shell, they would rise up and walk away.
00:12:42But I found it very difficult to keep my balance.
00:12:47NARRATOR: Darwin measured the creatures' extreme slowness.
00:12:52About four miles a day, he calculated.
00:12:55But the local people knew something else about the tortoises.
00:12:59(whispering):They could tell which island any tortoise came from just by looking at its shell.
00:13:06NARRATOR: Their shells differed depending on which island they lived on.
00:13:14Some tortoises had shells shaped like a dome.
00:13:19Others had shells arcing over their heads like a saddle.
00:13:30Others differed subtly in color.
00:13:34Or by how much the bottom of the shell flared out.
00:13:40Darwin had literally been sitting on a clue-- a way to understand the great diversity of life, but he didn't yet realize it.
00:13:57(birds calling) Instead, Darwin turned his attention to birds.
00:14:02The islands were full of what seemed to be a familiar assortment of species.
00:14:14So, he stuffed his collecting bag with what he thought were types of finches, grosbeaks, wrens and blackbirds.
00:14:24And then, after five weeks in the Galapagos, Darwin and theBeaglewent to other ports in the Pacific and finally set sail for home.
00:14:37On board, he started to sort through the vast number of specimens he had collected on the five-year voyage.
00:14:49But it was not until he returned to Britain that he was able to make sense of them.
00:14:55It began with a startling revelation.
00:14:59All the different birds he had collected actually were variations of a single type.
00:15:07CARROLL: He learns that those birds he had collected on the Galapagos actually represent 13 different species of finch.
00:15:18NARRATOR: What misled Darwin was that they looked radically different.
00:15:22Some had wide, tough beaks.
00:15:26Others had long slender ones.
00:15:27And these differences depended on which islands they lived on.
00:15:32CARROLL: Now, why would that be?
00:15:33Why would there be slightly different birds, slightly different species on different islands all in one part of the world?
00:15:42NARRATOR: Darwin now thought back to the Galapagos tortoises.
00:15:46They too differed from island to island.
00:15:55His brain began racing.
00:15:59CARROLL: Thoughts are starting to crystallize, take shape in his mind, bit by bit, bit by bit.
00:16:04He starts this process he describes as mental rioting.
00:16:08Just stream of consciousness where he's jotting down note after note after note.
00:16:12Thoughts as they occur to him.
00:16:13And finally, they converge on this one idea.
00:16:17NARRATOR: What Darwin now realized was that somehow, for some reason, species change.
00:16:35Originally, there must have been just one type of finch in the Galapagos, but over time it had diversified into many kinds, with different beak shapes.
00:16:47The same for the tortoises.
00:16:50One type of tortoise must have turned into many kinds, with different shells depending on which island they lived on.
00:17:04With this great insight, Darwin entered dangerous new territory.
00:17:10The standard view at the time was that God had created every species.
00:17:14And that what God had created was perfect and could not change.
00:17:20CARROLL: But Darwin said no.
00:17:22Why would the Creator bother with making slightly different finches for each of these different islands that all looked alike?
00:17:28NARRATOR: The prevailing view just didn't make sense.
00:17:38But this was only the beginning of Darwin's revolution.
00:17:43He turned his attention to the fossils he had collected in South America.
00:17:49One was of a giant sloth.
00:17:54Another was of a huge armadillo-like creature.
00:17:59These animals were extinct, but little sloths still existed in South America.
00:18:06And so did smaller armadillos.
00:18:09What could this mean?
00:18:10CARROLL: It dawned on him that they resembled each other.
00:18:14So, what he had found in the ground were the buried ancestors of the living animals of South America.
00:18:21NARRATOR: So, again, here was more evidence that species changed.
00:18:28Somehow, these ancient giants must have been transformed into the smaller creatures we see today.
00:18:39But what Darwin would later find out took this idea of how species change into a completely new league.
00:18:50In Victorian times, scientists routinely studied life-forms at the embryonic stage.
00:18:59How these tiny forms develop from just a single cell into an entire creature has long been seen as one of the wonders of nature.
00:19:11Watching a developing embryo is truly the most gloriousmiracle of nature.
00:19:16I mean, you know, no bologna.
00:19:18NARRATOR: What Darwin learned from studying the embryos amazed him.
00:19:24In snake embryos, you could see tiny bumps.
00:19:28The bony rudiments of legs.
00:19:31But these would never develop in the adult snake.
00:19:36Darwin wondered, "Were snakes somehow descended from animals with legs?" He learned that whales, which have no teeth as adults, had them as embryos.
00:19:57Those teeth disappeared before they were born.
00:20:03To Darwin, it had to mean whales were descended from creatures with teeth.
00:20:11But human embryos provided the most startling evidence.
00:20:17Under the microscope, tiny slits around the neck were clearly visible.
00:20:21Exactly the same structures were found in fish.
00:20:27But in fish, they turned into gills.
00:20:30In humans, they became the bones of our inner ear.
00:20:39Surely, this showed that humans must be descended from fish.
00:20:46It's an astonishing thought.
00:20:48JUDSON: I don't know about your ancestors, but mine included priests and, you know, the,the usual, the usual suspects.
00:20:56But the idea thatall of us have, have fish in our family tree, I think it's amazing.
00:21:01NARRATOR: And so, Darwin arrived at an astonishing conclusion, one that would become central to his understanding of the greativersity of life.
00:21:12Darwin had this amazingly bold idea-- the Tree of Life-- that all species were connected.
00:21:19And what it meant was, if you go far enough back in our family tree of humans, you'll come to fish.
00:21:27If you go far enough back in the family tree of birds, you'll come to dinosaurs.
00:21:34So that creatures that don't look anything at all like each other are actually deeply connected.
00:21:39No one came close to having this idea before Darwin.
00:21:45NARRATOR: This seemed to be an explanation for the vast diversity of animals.
00:21:50Beginning with a common ancestor, over time across generations, species could change dramatically.
00:21:59Some might add new body features.
00:22:01Others might drop them.
00:22:05Ultimately, one type of creature could be transformed into something utterly different.
00:22:10It's a process Darwin called "descent with modification." But it all begged a question.
00:22:21Why?
00:22:22What was making creatures change?
00:22:26Darwin needed clues.
00:22:29And he found them in a very surprising place.
00:22:35Dogs.
00:22:37Big, small, fat, tall.
00:22:42The British have long been obsessed by them.
00:22:47It was a full-blown love affair in Victorian England.
00:22:55Even Her Majesty was dog crazy.
00:23:00That love affair still continues today.
00:23:03Especially among scientists like Heidi Parker at the National Institutes of Health.
00:23:09So, one of the most interesting things about dogs is the kind of variation that you have.
00:23:15We have dogsthe size of groundhogs versus a dog like Zeppie,the Leonberger, who can get to bethe size of a mule deer.
00:23:22If we had that kind of size variation in humans, we would have people running around the size of Barbie dolls.
00:23:29NARRATOR: In his day, Darwin knew this range of sizes hadn't come about by chance.
00:23:35Through a careful process of selection, dog breeders mix different dogs with different physical traits to create new forms.
00:23:48Darwin was intrigued by what he was seeing breeders doing with the domestic dog.
00:23:52They could select for individual traits like size or shape, and they could actually change their breed.
00:24:00NARRATOR: The Whippet, for example, had been developed to chase rabbits.
00:24:06It was created by mixing greyhounds for speed, with terriers, used to hunt small game.
00:24:17And then it hit Darwin.
00:24:18Was there a similar form of selection going on in nature, but without human interference?
00:24:25Could natural selection explain the great diversity of life?
00:24:30CARROLL: It was brilliant.
00:24:32He took somethingvery familiar and comfortable, for example, animal breeding, and explained that the same sortof thing was going on in nature just at a little bit different pace and with no human guide.
00:24:49NARRATOR: But what could be carrying out selection in the wild?
00:24:53It was then that Darwin took a completely fresh look at nature.
00:24:58The Victorian view of nature was sentimental.
00:25:03Lambs lay down with lions.
00:25:06But Darwin's travels on theBeagle led him to a different view.
00:25:14For Darwin, nature was savage.
00:25:19Every creature was locked in a desperate struggle for survival, ultimately ending in death.
00:25:43The scale of death in nature is absolutely horrendous.
00:25:49And sometimes it's not just that there's a lot of death, but it's very unpleasant death.
00:26:06NARRATOR: But in all this brutal chaos, Darwin saw a pattern.
00:26:12CARROLL: Darwin showed that nature was a battlefield and that everything was in competition.
00:26:17And this brutal battle, this war of nature as Darwin described it, was actually a creative process.
00:26:29NARRATOR: The pattern that Darwin saw was that the creatures that survived were those best adapted to the specific environments they lived in.
00:26:39For instance, some could handle extremes of climate.
00:26:48Others were brilliantly honed killing machines, perfect for catching the available prey.
00:26:59Still others were perfect to evade those who might be hunting them.
00:27:09But how did this harsh view of nature explain the finches on the Galapagos, where Darwin observed that the birds on different islands had different beak shapes?
00:27:21Somehow, those different beaks must be helping the finches survive.
00:27:31TABIN: The finches of the Galapagos Islands have beaksof many sizes and shapes.
00:27:37And there's a reason for that.
00:27:38They use their beaks as tools.
00:27:40Now, if you think of the type of tool you would want to crush a seed that's very tough, but is the food that you really like, you'd want a beak like this, which is the type of beak the ground finch has.
00:27:55On an island where the only food is seeds that are hard to crack, a short, powerful beak will mean a finch will survive.
00:28:09But on another island, the available food isn't seeds but flowers.
00:28:15If you wanted to get into narrow spaces to get pollen and nectar that are very hard to get at, you wouldn't need a big, strong beak, you'd need a probing beak.
00:28:24NARRATOR: So, on a different island, where you have a different food source, you have a different beak shape.
00:28:30And this pattern was repeated across the Galapagos.
00:28:35It seems that the finches' beaks had altered to fit the diet of each particular island.
00:28:42And that was how one original type of finch had been transformed into many.
00:28:57But how had these changes come about?
00:29:05Here, Darwin had another clue.
00:29:10He could see it in his own family.
00:29:14As every parent knows, no two children are ever exactly the same.
00:29:20Charles looked different from his brother, Erasmus, even though they shared the same parents.
00:29:26Charles's children looked a bit like him and his wife Emma.
00:29:34But they too looked different from each other.
00:29:37That was something he called variation.
00:29:42He realized that not every individual was the same, stamped out like a toy from a press.
00:29:47Buthere was variation.
00:29:49NARRATOR: Darwin realized that variation must be the starting point for change in nature.
00:29:56In any generation, the animals in a litter are never quite the same.
00:30:04And in the wild, such a tiny variation might make all the difference between life and death.
00:30:13Two penguins, for instance, might differ a tiny bit in the thickness of their blubber-- a big factor if you live in extreme cold.
00:30:23In a harsh climate, the environment will select who will live and who will die.
00:30:31And slowly, Darwin suggested, over many, many generations, these tiny variations would allow the fit to get fitter and the unfit would vanish.
00:30:47These variations accumulate and eventually, new species branch off.
00:30:53This is evolution by natural selection.
00:30:57It is one of the keys to how new species are formed.
00:31:05And so, in 1859, after years of painstaking research, Darwin finally published his masterwork, On the Origin of Species.
00:31:17It is still impossible to overstate its importance.
00:31:21It was really a quantum advance in understanding.
00:31:25It shook people up, it changed the way people thought.
00:31:29NARRATOR: Gone was the idea that all species were created perfect and immutable, taken as an article of faith.
00:31:37In its place, Darwin provided a proper scientific theory, based on facts and observation.
00:31:47It is much more thanthe presentation of simply the idea of natural selection.
00:31:53It is a, it's a vision of how evolution by natural selection works.
00:31:57150 years later, his theory has stood the test of time.
00:32:03CARROLL: What's amazing is that Darwin got so much right.
00:32:06His ideas largelystay intact today.
00:32:13NARRATOR:But Darwin himself acknowledged that therewere holes in his theory.
00:32:21He didn't actually know how it worked.
00:32:29What was happening inside a creature's body that makes it change?
00:32:37But now, at last, modern science is providing the answers through a hidden mechanism that Darwin knew nothing about.
00:32:56Arizona's Pinacarte Desert is a harsh and brutal place.
00:33:02Especially if you're a rock pocket mouse.
00:33:08NACHMAN: They're the Snickers bar of the desert.
00:33:11They really are,they're eaten by everything.
00:33:13They're probably eatenby foxes and coyotes and rattlesnakes, owls.
00:33:20NARRATOR: Weighing just half an ounce, this mouse could never fight off these large predators.
00:33:25Its best hope for survival is camouflage.
00:33:30Not surprisingly, its fur matches the color of the Pinacarte rocks.
00:33:36But in some sections of the desert, the environment is different.
00:33:44Ancient volcanoes erupted and now the desert is a patchwork of dark lava and light rock.
00:33:53But of course, a light mouse on a dark rock is easy pickings.
00:34:01So, something has happened that Darwin might have predicted.
00:34:10The mice now living on the dark rocks have evolved darker fur.
00:34:16Those that stayed on the light rocks remain light.
00:34:27Michael Nachman was fascinated.
00:34:29How had this happened?
00:34:31To find out, he first needed to catch some mice.
00:34:35So, with Sean Carroll, he visits a line of traps he set the previous night.
00:34:39NACHMAN: All of the dark ones have a white underbelly and presumably, there's no selection for dark on the belly because predators are going, coming from above.
00:34:47NARRATOR: This much Darwin could have done.
00:34:49Find some mice and compare the color of their fur to their environment.
00:34:54But Nachman can now do something that Darwin never could.
00:34:57He can look inside the animal's DNA.
00:35:11The study of DNA is one of the great triumphs of modern science.
00:35:19It has taken our understanding of how creatures evolve and develop to a level that Darwin could never have dreamed of.
00:35:29CARROLL: The DNA molecule is one of the real secrets of life.
00:35:32It's a perfect system for storing the vast amounts of information that's necessary for building all kinds of creatures.
00:35:42NARRATOR: DNA consists of one long molecule spiraling around in a double helix.
00:35:52That helix is, in turn, made up of four smaller molecules, called by the letters G, A, T and C.
00:36:04DNA can be found in the cells of every living thing on earth.
00:36:12JUDSON: The thing about DNA that I think is remarkable is that the molecule itself is so elegant.
00:36:20With a small number of letters, you can say almost infinite words.
00:36:27NARRATOR: And that is the key.
00:36:31DNA is a code and its double strand contains all the information to make living things grow and develop.
00:36:41Lined along each DNA molecule are ranged special sequences of this code that form our genes.
00:36:56Many genes get translated into proteins.
00:37:03And these proteins make the stuff of our bodies.
00:37:08One protein makes hair.
00:37:11Another makes cartilage.
00:37:13Others make muscle.
00:37:16CARROLL: What makes DNA so amazing is that it just contains four letters, but all sorts of combinations of those four letters contains all the information for making all the creatures that are on the planet.
00:37:29NARRATOR: It's a gene that determines whether our eyes are blue or not.
00:37:35Another gives us freckles.
00:37:37Another gives us dimples.
00:37:42But DNA has one other vital quality.
00:37:48It doesn't stay the same.
00:37:53(crying) When a baby is conceived, the fertilized egg receives half its DNA from the mother and half from the father, creating wholly new combinations.
00:38:07It's why we look a bit like our parents, but also different.
00:38:17Another way that DNA can change is mutation.
00:38:25CARROLL: Mutation is a critical ingredient in the recipe for evolution.
00:38:28Without mutation, everything would stay constant generation after generation.
00:38:33Mutation generates variation, differences between individuals.
00:38:39NARRATOR: Mutations can happen as our DNA copies itself when our cells divide and our bodies develop.
00:38:48An "A" for instance, can be replaced by a "G" or a "C" by a "T." This can cause minute changes that no one is even aware of.
00:39:01But when mutations occur in the cells we pass down to our children, they can cause big changes.
00:39:13Like turning a light-colored mouse dark.
00:39:18"Mutation" seems to mean thatsomething bad has happened.
00:39:22Well, mutationsare neither good or bad.
00:39:24Whether they are favored, or whether they are rejected,or whether they're just neutral depends upon the conditions an organism finds itself.
00:39:31So for the pocket mouse, a mutation that caused the mouse to turn black...
00:39:35That is good if you're living on black rock, it's bad if you're living out in the sandy desert.
00:39:43NARRATOR: It was that mutation, the one that turned a light-colored mouse dark, that Michael Nachman was hunting for.
00:39:57Back in the lab, he began the painstaking business of comparing the genes of the two types of mice, trying to pinpoint any differences.
00:40:07NACHMAN: Science is fun when you really don't know what you're going to find.
00:40:18NARRATOR: One by one the genes in the two mice proved identical.
00:40:25But then, in one gene, he found something.
00:40:31There were four places where the sequence of "A's," "T's," "C's" and "G's" were different..
00:40:40When a mouse is born with these mutations, its fur grows dark.
00:40:48And that means it can survive on the dark rocks when others would not.
00:40:55Here was a clear example of evolution and natural selection at work.
00:41:04I think Darwinwould have been delighted to know thatwe can find the genes that are responsiblefor evolutionary change.
00:41:14NARRATOR: And this was just one of many links that have been found between genetic mutations and evolution.
00:41:23Scientists can now pinpoint a range of examples of evolution in action.
00:41:33The Colobus monkey can see in color because of a mutation in one gene.
00:41:37It can now tell nutritious red leaves from tough, old green ones.
00:41:44A genetic glitch gave this Antarctic fish a potent antifreeze in its blood.
00:41:51So it can survive in the icy waters when others cannot.
00:41:56So powerful was this link between genetic mutation and evolution that an idea took hold.
00:42:04To understand how evolution works, all you need to do is compare creatures' genes.
00:42:26One might think that you could understand all of evolution simply by mapping the genes of every creature.
00:42:31Identify all the genes, identify all the differences and you could explain the differences between, say, mouse and monkeys and humans.
00:42:41NARRATOR: So when the Human Genome Project began in 1990, the scientific world was on tenterhooks.
00:42:48All three billion letters of our DNA were going to be identified in order.
00:42:53In parallel, the DNA of some animals and plants was also being sequenced.
00:42:58Surely, this would be a quantum leap in our understanding of how different life-forms evolved.
00:43:06With this came another idea: That complex animals like us would have many more genes than simpler ones.
00:43:14Here we are, the most complex and sophisticated animal on the planet, right?
00:43:19You might think that would require a whole lot more genetic information.
00:43:22NARRATOR: The betting was on.
00:43:24Just how big would our genome be compared to other life-forms?
00:43:29There were estimatesthat humans would have between, let's say,80,000 and 120,000 genes.
00:43:43NARRATOR: So when the final answer came in 2003, it was a shocker.
00:43:5223,000 genes-- the same number as a chicken...
00:44:01less than an ear of corn.
00:44:06LEVINE: I mean, people were freaked out by the relativelysmall number of genes.
00:44:10It's down to something like22,000 or 23,000 protein-coding genes in the human genome.
00:44:17The simple nematode worm has about that same number.
00:44:20And there are plants that have considerably more genes than the glorious human genome.
00:44:27The whole human genome project has been a humbling experience, as we've discovered that, actually, it doesn't take as many genes to make a human as we had all hoped.
00:44:35NARRATOR: And it wasn't just that we had so few genes, but many of our key genes were identical to those of other animals.
00:44:47Huge though the breakthrough had been, the genetic revolution had opened up a whole new set of puzzles.
00:44:54As a solution to the mystery of how evolution works, genes and their mutations were only part of the story.
00:45:05There had to be something else more subtle and more mysterious going on.
00:45:11CARROLL: We have to explain then, "How do you get all these differences if you have really similar sets of genes?" NARRATOR: The quest to uncover what Darwin never knew would have to start again.
00:45:28The first tantalizing clues would come from those life-forms that Darwin himself had studied: embryos.
00:45:38Look at these embryos.
00:45:40It is almost impossible to telljust days after conception which is the chicken,the turtle, the bat, the human.
00:45:49They look almost the same.
00:45:55Only as they grow does it become clear which is which.
00:46:00Darwin wondered, as scientists do today, "How could they start out so similar and end up so different?" LEVINE: There is something profound about what the embryo was telling us.
00:46:14And we have rediscovered what Darwin was talking about all along, that the embryo's where the action is.
00:46:23In terms of animal diversity, it is the platform for diversity.
00:46:31NARRATOR: What fascinates modern biologists is that all these different animals don't just look the same, they are using virtually the same set of key genes to build their bodies.
00:46:48The body plan genes determine where the head goes, where the limbs go, and what form they take-- whether they are arms, legs or wings.
00:47:03Another set of genes determines an animal's body patterning: the blotches, the stripes and spots.
00:47:10It is the same genes at work in every creature from the leopard to the peacock to the fruit fly.
00:47:21And yet they produce radically different results.
00:47:29This has led scientists to a crucial insight about how animal bodies have evolved.
00:47:35It's not the number of genes that counts.
00:47:40CARROLL: It's not the genes you have, but how you use themthat generates the great diversityof the animal kingdom.
00:47:47NARRATOR: Finding out just how these same genes are used to create such amazing diversity has been the work of Sean Carroll and an unlikely hero of modern science.
00:48:03The fruit fly.
00:48:08As much as I'd like to study the mammals of the African Savannah, they make poor choices for laboratory animals.
00:48:13They're large, expensive and they reproduce very slowly.
00:48:16To get data, we have to find the simplest examples to the phenomenon we want to understand.
00:48:24NARRATOR: But the humble fruit fly does weird and wonderful things.
00:48:32This fruit fly is dancing for sex.
00:48:37A rapt female takes in the show.
00:48:42She's particularly besotted by the dark spots on the male's wings.
00:48:49Watching it all is an equally besotted Sean Carroll.
00:48:53CARROLL: You might think them just be annoying, but they're really charming.
00:48:56And the males of this species does a rather elaborate courtship dance, where he displays these spotted wings in front of the female.
00:49:04To us, it's as magnificent as what a peacock does.
00:49:12NARRATOR: But in some species of fruit fly, the males don't have wing spots.
00:49:19CARROLL: There's another fruit fly species that's different from the spotted species in two important ways: it doesn't have spots on its wings and it does a lot less dancing.
00:49:30NARRATOR: Here, then, is a classic evolutionary puzzle.
00:49:34Why does one type of fly have spots and the other doesn't?
00:49:38Sean Carroll wanted to know.
00:49:40What is going on in their genes that makes them different?
00:49:44CARROLL: So we wanted to take apart the genetic machinery for making wing spots to understand how those wing spots evolved.
00:49:54NARRATOR: Carroll began the process of sifting through the two types of flies' DNA.
00:50:00He had one clue to set him on his way.
00:50:04He already knew the gene that codes for the black wing spots.
00:50:08He calls it the "paintbrush gene." But surprisingly, when he compared the genes of the two flies, they both had that gene.
00:50:21And yet, only one had spots.
00:50:27CARROLL: When we look at that gene in the two species, really they both have this paintbrush gene.
00:50:32So the big difference is not having the gene, it's how they use it.
00:50:35One species uses it in the wing to make spots.
00:50:41The other one doesn't.
00:50:46NARRATOR: So why did the paintbrush gene create spots in one type of fly, but not in the other?
00:50:56In search of answers, Carroll turned to one of the least understood regions of DNA: the vast stretches that were once known as "junk." It has been called the dark matter of the genome.
00:51:18Mysterious.
00:51:20Uncharted.
00:51:22Strange.
00:51:24The vast bulk of the double helix, some 98% of it, doesn't code for proteins, which make the stuff of our bodies.
00:51:33The genes which do, comprise just two percent.
00:51:40Even now, no one is sure what much of this huge non-coding area actually does, but it has long beckoned evolutionary detectives, like Sean Carroll.
00:51:50So, this is a bend.
00:51:52That's the fragment to test. Yeah.
00:51:53NARRATOR: Carroll had already learned that the paintbrush gene itself was identical in the two types of fly.
00:51:59So he extended his search through their DNA.
00:52:02And in one place, just outside the paintbrush gene, he found an important clue.
00:52:11A stretch of DNA that was different in the fly with wing spots.
00:52:15What could this mean?
00:52:21So Carroll conducted an experiment.
00:52:26He decided to put that mysterious stretch of DNA that he had found in the spotted fly in the unspotted fly.
00:52:35To help him see if it had any effect, he attached it to a gene from a jellyfish, a gene that codes for a protein that makes the jellyfish glow.
00:52:45We cut the DNA up into little pieces, and we hook it up to a protein that glows in the dark.
00:52:50And then we inject that into the unspotted fly.
00:52:56NARRATOR: And then, something remarkable happened.
00:53:02CARROLL: When we looked at those unspotted flies, we see now their wings are glowing in the dark with spots.
00:53:09NARRATOR: Somehow that mysterious stretch of DNA had turned on the paintbrush gene in the unspotted fly's wings.
00:53:17Once spotless, now it had luminous spots.
00:53:22CARROLL: Bingo.
00:53:23We'd found the piece of DNA that mattered.
00:53:27NARRATOR: Carroll had found something that is revolutionizing our understanding of how different animal bodies have evolved.
00:53:34A piece of DNA called a "switch." Switches are not genes.
00:53:43They don't make stuff like hair, cartilage or muscle.
00:53:48But they turn on and off the genes that do.
00:53:55CARROLL: Switches are very powerful parts of DNA, because they allow animals to use genes in one place and not another, at one time and not another.
00:54:06And so, choreograph the spots and stripes and blotches of animal bodies.
00:54:12NARRATOR:In the case of the fruit fly, it's a mutation-- a change in justa few letters of the DNA that has caused the paintbrush gene to be switched on.
00:54:25And so, a whole new species with wing spots has been created.
00:54:32But switches are now explaining far more than that.
00:54:37They are helping to solve many perplexing evolutionary questions.
00:54:44Like how one creature can become another creature by losing it legs.
00:54:57It all goes back to what Darwin had seen in the snake embryo.
00:55:05The rudiments of leg bumps.
00:55:11This convinced him that a snake must have evolved from some four-legged animal.
00:55:18Over the years that same mysterious process, the losing of legs, has been seen in other creatures.
00:55:26Like the whale.
00:55:30Its front flippers have all the bones of a land creature's arm, even the fingers.
00:55:39And further back in its body...
00:55:43...it has the vestiges of a pelvis.
00:55:49Clearly, it is descended from an animal that walked on the land.
00:55:53KINGSLEY: Lots of animals have evolved to slitherthrough the ground like snakes.
00:55:58Other animals slitheror swim through the water like whales.
00:56:01So if you need a streamlined body, it's good to get rid of these things that stick out from the body, like limbs.
00:56:11NARRATOR: Like the whale, the manatee is another huge mammal that lives in the sea.
00:56:18And it, too, has lost its hind legs.
00:56:23How?
00:56:30Darwin could never have answered that question.
00:56:34But now, thanks to our understanding of how DNA is switched on and off, and a very small fish, we are getting a little closer.
00:56:47In this lake in British Columbia, there is a creature that really shouldn't be here.
00:56:54A stickleback.
00:56:59Most sticklebacks live in the ocean.
00:57:03But some 10,000 years ago, a few were left stranded in this lake, cut off from the Pacific.
00:57:14And over the years, they have evolved.
00:57:27The ocean stickleback has a pair of fins on its belly that are like spikes.
00:57:34They are for defense.
00:57:37The spikes make the stickleback hard to eat.
00:58:01But the lake sticklebacks have lost those spikes on their bellies.
00:58:12And it's this that intrigues researchers David Kingsley and his colleague, Dolph Schluter.
00:58:20To understand what's behind it, they first identified the gene that makes the stickleback's spikes.
00:58:26It's one of those key body plan genes and, not surprisingly, they found it to be identical in both the ocean and the lake stickleback.
00:58:36The question was, why hadn't in been turned on in the lake stickleback, which had lost its spikes?
00:58:43Kingsley felt the answer might lie in a switch.
00:58:47KINGSLEY: We know these genetic switches exist, but they're still very hard to find.
00:58:52We don't have a genetic code that lets us read along the DNA sequence and say, "There's a switch," to turn a gene on in a particular place.
00:58:59NARRATOR: But eventually, hunting through the vast stretch of DNA that does not code for proteins, he found it.
00:59:07A section of DNA that had mutated in the lake stickleback.
00:59:11These mutations meant that the switch was broken.
00:59:15It didn't turn on the gene that makes spikes.
00:59:24But this work may have implications far beyond sticklebacks.
00:59:29They are convinced that there is a link between the stickleback losing its spikes and other creatures, like a manatee, losing their legs.
00:59:39And they have two tantalizing clues.
00:59:43One-- the same body plan gene that is responsible for the stickleback spikes, also plays a role in the development of the hind limbs.
00:59:54The second clue is more tentative.
00:59:59The lake stickleback may have lost its spikes, but evolution has left behind some tiny remnants...
01:00:08the traces of bones, and they are lopsided-- bigger on the left than on the right.
01:00:16KINGSLEY: We thought, "Wouldn't it be amazing "if in fact this classic unevenness is "the signature of using the same gene to control hind limb loss in an incredibly different animal?" searching for this lopsided pattern.
01:00:44And they found it.
01:00:45In box after box of manatee skeletons, they saw pelvic bones that were bigger on the left and smaller on the right.
01:00:55Right now, Kingsley and his team are looking for the same switch in the manatee that caused the lake stickleback to lose its spikes.
01:01:03And if they find it, they will have a powerful explanation for something that baffled Darwin-- how creatures like manatees, kes can evolve away their legs.
01:01:16But all this begs another question: If switches can play such a profound role in the different shapes and patterns of animal bodies-- from wing spots, to spikes to hind legs-- what is throwing those switches in the first place?
01:01:38Researchers would see the answer in animals very familiar to Darwin-- those Galapagos finches.
01:01:48Arkat Abzhanov and Cliff Tabin have spent years trying to find out exactly how those Galapagos finches got their different beaks.
01:01:57Their starting point was what they had learned from Darwin himself.
01:02:04Their beaks were vital to the birds' survival.
01:02:07On an island where the main food was seeds, finches had short, tough beaks for cracking them open.
01:02:14On an island where the main food was from flowers, birds had long pointy beaks for sucking up nectar and pollen.
01:02:25And they knew something else.
01:02:29The finches are born with their beaks fully formed.
01:02:34So the answer to why they had such different beaks must lie in something that happened to them as embryos in the egg.
01:02:42TABIN: Something amazing is happening inside those eggs.
01:02:45Genes are turning onand turning off.
01:02:48And depending on exactlyhow they turn on and off will determine what type of finch is formed.
01:02:57RRATOR: To find out just what was going on, the researchers first had to collect some eggs.
01:03:04(whispers): There she is.
01:03:05She just came back. Yeah.
01:03:08To lay eggs.
01:03:09It's really likely that she already has a clutch; great.
01:03:13She's coming out.
01:03:14NARRATOR: Abzhanov checks a ground finch nest and finds a single egg.
01:03:20He won't remove it, because the mother might abandon the nest.
01:03:26Another nest already has three eggs.
01:03:29He takes one for his research, as he knows the mother will lay a replacement.
01:03:36The team collects several eggs, with embryos at different stages of development.
01:03:42That way they will be able to chart exactly how the different beaks grow.
01:03:49Back in the lab, they can begin the process.
01:03:58This cactus finch embryo is well on the way to its signature long, pointy beak.
01:04:04And this ground finch embryo is growing a short, thick beak.
01:04:10What we wanted to do was try and understand the genes that were involved in making the beak the way it was-- making a big, broad thick beak different from a long, thin beak or a short, thin beak.
01:04:20NARRATOR: They concentrated on a group of genes known to control the growth of birds' faces.
01:04:28As they looked, they saw something intriguing.
01:04:37One particular body plan gene became active in the ground finch with the short, thick beak, on the fifth day of development.
01:04:44But it didn't go to work in the cactus finch with its long, slender beak for another 24 hours.
01:04:53This was a revelation.
01:04:55The same genes were responsible for the beaks in all types of finch.
01:05:00Any differences were in timing and intensity.
01:05:03TABIN: We've got it! We nailed it!
01:05:05It's the same genesin making a sharp, pointy beak or a big, broadnut-cracking beak.
01:05:11What's essential,what makes the difference, and all the difference, is how much you turn the gene on, when you turn it on, when you turn it off.
01:05:21NARRATOR: And the revelations didn't end there.
01:05:24There was something special about this gene.
01:05:27Like all body plan genes, it doesn't actually make the stuff of our bodies.
01:05:33It didn't make the cartilage for the finches' beaks.
01:05:38It throws switches.
01:05:40And the switches then turn on or off the genes that do make the beak.
01:05:46CARROLL: These are a different type of gene.
01:05:49They're genes that boss other genes around.
01:05:53Scientists now realize that not all genes are created equal.
01:05:57Some make the stuff of our bodies.
01:06:01And switches are needed to turn many of these "stuff" genes on and off.
01:06:05The body plan genes are what throw these switches, which tell the stuff genes what to do and when.
01:06:13This subtle choreography can have profound effes on how different animal bodies are formed.
01:06:21And this knowledge is helping us solve perhaps the biggest Darwinian puzzle of all: the mystery of the great transformations.
01:06:35It all goes back to Darwin's idea of the tree of life.
01:06:42That all life-forms are ultimately related.
01:06:44And from the earliest common ancestor over billions of years, they have changed and diversified so that creatures that started out looking the same evolved to become completely different.
01:07:01And scientists have made some amazing connections.
01:07:07That dinosaurs share a common ancestor with birds.
01:07:12And that a fish must have been the ancestor of all four-limbed creatures-- even us.
01:07:22Of all his ideas, this was probably Darwin's most astonishing.
01:07:29CARROLL: It was one thing to grasp how two species of finch could become different, how their beak shapecould change.
01:07:35That was a small step.
01:07:36But what aboutthe big differences?
01:07:38The differences, say, betweenthe fish that swim in the sea and the animals that walk on land?
01:07:42How did those changes take place?
01:07:45NARRATOR: Over the years, evidence for these great transformations has been found.
01:07:52For instance, just a year after Darwin published On the Origin of Species, a fossil called "archaeopteryx" was discovered.
01:08:02It had features of both birds and dinosaurs.
01:08:08And Darwin had seen equally persuasive evidence in embryos.
01:08:14Those slits in the ear of all land creatures, even humans.
01:08:18In us, they become tiny bones in the inner ear.
01:08:27But in fish, they become gills.
01:08:31A tantalizing hint that land animals must be descended from fish.
01:08:37But the stumbling block has always been how.
01:08:42How could a fish develop legs and walk on land?
01:08:52Darwin had no idea.
01:09:02But Neil Shubin was determined to tackle that problem.
01:09:07SHUBIN: It captured my imagination.
01:09:08I mean, here's a fin and on the other side was a limb.
01:09:11And they lookeddifferent in many ways.
01:09:13And I thought, "Well, whata first-class scientific problem to devote my research to." And I've been devoting pretty much my research to it ever since, over 20 years.
01:09:25NARRATOR: The first stage in Shubin's quest was to find a fossil.
01:09:30If Darwin were right, somewhere out there, there had to be a transitional form, a fossil that was part fish, but had the beginning of legs.
01:09:41But where to look?
01:09:47He had one clue.
01:09:48The fossil record shows that creatures with legs first appeared some 365 million years ago.
01:09:56Before that, they were only fish.
01:10:05So, summer after summer, Shubin set up camp on Ellesmere Island, just a few hundred miles from the North Pole.
01:10:13It has exposed rock from that crucial transitional time.
01:10:17The scientist's own video shows how remote and bleak the place was.
01:10:23SHUBIN: It's cold.
01:10:24It's about freezing every day over the summer.
01:10:27Winds are high.
01:10:28They can get up to 50 miles an hour.
01:10:31There are polar bears there.
01:10:32We have to prepare ourselves by carrying guns.
01:10:34It's a beautiful place. You've got to love it.
01:10:36It's my summer home.
01:10:40NARRATOR: Each expedition was costly, but after three of them there was little to show for their efforts.
01:10:46A fourth trip seemed pointless.
01:10:52SHUBIN: I remember having a conversation with my colleagues saying, "Well, should we go? Is this really a waste of money?" This was our do-or-die moment.
01:11:02And we almost didn't go.
01:11:06NARRATOR: But they decided to try one last time.
01:11:15After three days, they still hadn't found anything.
01:11:22Then, just when no one was expecting anything to happen...
01:11:29A colleague was cracking rocks and I was working about five feet from him.
01:11:32And I hear, "Hey! Hey, guys, what's this?" Sticking out of the cliff was the snout of fish.
01:11:45And not just any fish, a fish with a flat head.
01:11:49By seeing a flat-headed fish in rocks about 375 million years old...
01:11:56we knew we had found what we were looking for.
01:12:00NARRATOR: A flat snout with upward staring eyes-- the signature of an animal that pushes its head out of the water.
01:12:08And for that, it would have needed something like arms.
01:12:13SHUBIN: What we did at that moment was all jump around high-fiving.
01:12:16It was, uh, you know, there were only six of us in the field that time, so it was quite a scene.
01:12:24NARRATOR:Back at home, Shubin and his team got to work, examining their375-million-year-old fossil.
01:12:36They named their new finding "Tiktaalik," an Inuit word for a freshwater fish.
01:12:43Tiktaalik is a perfect transitional form.
01:12:47Much of its body is that of a fish.
01:12:50It's covered in scales.
01:12:54But it also had something very un-fishlike...
01:13:02an arm-like fin, or perhaps a fin-like arm.
01:13:12Tiktaalik had the bone structure that is seen in the arms and legs of every four-limbed animal.
01:13:20One big bone at the top, two bones underneath, leadin a cluster of bones in the wrist and ankle.
01:13:31It's the same pattern that is found in everything from sheep, to sheepdogs, to Shubin himself.
01:13:39You now have an animal that can push itself up off the substrate, either on the water bottom or on land.
01:13:49NARRATOR: One obvious question was: Why had Tiktaalik evolved this new structure?
01:13:58One possible answer is suggested by other fossils found near it.
01:14:05There are large predatory fish about ten to 15 feet long living alongside Tiktaalik.
01:14:13NARRATOR: Tiktaalik was prey.
01:14:15To survive, it had few choices.
01:14:23You can get big, you can get armor or you can get out of the way.
01:14:28NARRATOR: Shubin thinks Tiktaalik got out of the way.
01:14:33With those arm-like fins, it could have dragged itself to safety on land or in the shallows.
01:14:43But this was only half the answer.
01:14:48What it doesn't show us is the actual genetic mechanism, the genetic recipe that builds a fin into that which builds a limb.
01:15:02NARRATOR: At 375 million years old, Tiktaalik's DNA had vanished long ago.
01:15:10Shubin needed a next-of-kin, a fish relative that was still alive.
01:15:18SHUBIN: What we needed was a creature that was in the right part of the evolutionary tree, but also a fish that has a very fleshy fin.
01:15:26So the search was on.
01:15:31NARRATOR: A number of fish fit the bill.
01:15:35But Shubin favored one in particular...
01:15:42the paddlefish.
01:15:44SHUBIN: The paddlefish is a really weird fish.
01:15:46They developed this really long snout.
01:15:49And they're really voracious.
01:15:50They eat each other.
01:15:51So oftentimes you'll lose a lot of your fish when they swim together, because they'll eat each other.
01:15:57NARRATOR: Living in the shallow waters of the Mississippi, it's also a living fossil.
01:16:04Scientists have spent years working out the relationships between different species of fish and they know that the paddlefish is one of the last survivors of the class to which Tiktaalik once belonged.
01:16:17But unlike Tiktaalik, the paddlefish is in plentiful supply.
01:16:22Paddlefish is a common source for caviar.
01:16:24So we'd get our paddlefish from caviar farms.
01:16:29NARRATOR: Intriguingly, even though Tiktaalik is extinct, the paddlefish is actually the more primitive form.
01:16:38Its fins bear far less relation to an arm or leg than Tiktaalik's.
01:16:43And because they are related, the two kinds of fish should share the same genes.
01:16:53So Shubin began looking at paddlefish embryos, hunting for the genes that built its fins.
01:17:03And soon he zeroed in on one particular group of body plan genes called Hox genes.
01:17:17Hox genes have been found in all complex animals from the velvet worm, that dates back some 600 million years, to the modern human.
01:17:30And in all that time, the letters of their Dna have remained virtually unchanged.
01:17:37They are aristocrats of the gene community, near the very top of the chain of command.
01:17:43They give orders that cascade through a developing embryo...
01:17:49activating entire networks of switches and genes that make the parts of the body.
01:18:01They are absolutely critical to the shape and form of a developing creature.
01:18:06CARROLL: These genes determine where the front and the back of the animal's going to be-- the top, the bottom,the left, right, the inside, the outside--where the eyes are going to be, where the legs are going to be,where the gut's going to be-- how many fingers they're going to have.
01:18:19NARRATOR: Shubin found that Hox genes had a key role in the formation of paddlefish fins.
01:18:31One set of Hox genes orders the first stage of fin development-- a sturdy piece of cartilage that grows out from the torso.
01:18:43Amazingly, in all four-limbed animals, even us.
01:18:48Exactly the same genes create the long upper arm bone.
01:18:57In the paddlefish, another set of Hox genes command the next stage of fin development.
01:19:04Again, exactly the same genes control the growth of our two forearm bones.
01:19:16Finally, the same genes, working in a different order, make the array of bones at the end of the fin.
01:19:24The same sequence of the same genes makes our fingers and toes.
01:19:33This was a massive revelation.
01:19:41Suddenly the origin of creatures with arms and legs didn't seem such a huge leap after all.
01:19:48If the same genes were at work in Tiktaalik, then many of the genes needed to make legs and arms were already being carried around by prehistoric fish.
01:20:04All it needed was a few mutations-- a few changes to the timing and order of what was turned off and on, and a fin could become a limb.
01:20:17SHUBIN: Oftentimes the origin of whole new structures in evolution doesn't involve the originof new genes or whole new genetic recipes.
01:20:25Old genes, old genetic pathways can be reconfigured to make marvelously wonderful new things.
01:20:43NARRATOR: So it is now possible to answer what Darwin didn't know and explain how all four-legged creatures could be descended from fish.
01:21:00Around 375 million years ago, a creature like Tiktaalik was under attack...
01:21:09harried by predators.
01:21:21But some random changes to the activity of the Hox genes led to its fins, developing a structure like a limb.
01:21:33Tiktaalik could now haul itself out of danger, onto dry land.
01:21:44On land, it would have found a world of plants and insects...
01:21:52a world ripe for colonization...
01:21:57a world perfect for animals with arms and legs.
01:22:07And so, over millions of years, these new limbs evolved, changed and diversified.
01:22:15Some became adapted for running.
01:22:20Others for flying.
01:22:26Some for digging.
01:22:33Others for swinging.
01:22:37And so four-limbed creatures took over the world in a multitude of different ways.
01:22:48And all because of some changes to an ancient set of genes.
01:22:55And this is the true wonder of where our new understanding of DNA has led us to.
01:23:03There are genes that make the stuff of our bodies, switches that turn them off and on, and still other genes that give those switches orders.
01:23:14Together in a complex cascade of timing and intensity, they combine to produce the amazing diversity of life on this planet.
01:23:27That truly is something that Darwin never knew.
01:23:36But can this new science also explain perhaps the most fundamental question of all?
01:23:43What makes us human?
01:23:52The scope of human activity is simply astounding.
01:23:58What fascinated me were all the crazy thingsthat humans do.
01:24:01You look around the world, and if there is something bizarre and interesting that you could be doing, humans are up to it somewhere in the world.
01:24:12And when you look at all of this, you just have to ask yourself, what makes us special?
01:24:17What is the basis for this humanness?
01:24:24NARRATOR: For all nature's wonders, the achievements of the human mind are truly unique.
01:24:33We are the only species to think about what others think about us, to punish those who have harmed others, to create art...
01:24:46music...
01:24:48architecture...
01:24:52to engage in science...
01:24:55medicine...
01:24:59the microchip.
01:25:06Only we can destroy millions at the push of a button.
01:25:16Hardly surprising, then, that for centuries we thought that humans were different from all other species, better, created in the image of God.
01:25:30But then Darwin began to draw conclusions from evidence like gill slits in human embryos that showed that we were descended from fish.
01:25:45(people exclaim) But it was when he drew parallels with other close relatives that he got into real trouble.
01:25:55CARROLL: Shortly after Darwin returned from his voyage, in London, an orangutan named Jenny went on exhibit.
01:26:00And this was a huge sensation.
01:26:02This was the first great apeto be exhibited in captivity.
01:26:05And Darwin was absolutely taken with how she was sort of childlike in her ways.
01:26:10And he saw a lot of human behavior in the way this orangutan behaved.
01:26:19NARRATOR: When Darwin suggested that human beings must actually be descended from apes, he was savaged.
01:26:26He was accused of attacking that core belief that humankind had been created in the image of God above all other creatures.
01:26:35But today the idea that we share a common ancestor with apes is completely accepted in biology.
01:26:43Instead, as a result of having sequenced the genomes of both humans and apes, we face a very different puzzle.
01:26:51Katie Pollard is an expert on chimp DNA.
01:26:55Given all the obvious differences between humans and chimps, you might expect our DNA to be really different.
01:26:59But in fact, it's more like 99% identical.
01:27:08NARRATOR:Just a one-percent difference in the DNA of humans and chimps.
01:27:16The mystery facing modern science is not how can such different animals be related, but how can such closely related species be so different?
01:27:27That really is something that Darwin never knew, but slowly, scientists are starting to find the answers.
01:27:38And one answer begins with insights into the genetics of a key human organ, our hands.
01:27:48The human hand is a marvel, nimble and dexterous.
01:27:56Nothing quite like it exists anywhere else in nature.
01:28:00It offers us a unique combination of precision and power, and much of that is down to one particular digit, our thumb.
01:28:12One of the features of the humanhand is our ability to touch all four fingerswith the thumb.
01:28:21And that allows us to make grips like this, gives us a lot of precision.
01:28:26The power grip is the ability to put a lot of strength into this sort of contact.
01:28:33So if you're holding a ball, you're basically pinching it, and we can put a lot of strength into that.
01:28:42NARRATOR: The better to throw a fastball with.
01:28:49Finding out why we have such versatile hands compared to our nearest relatives is the task of Jim Noonan at Yale University.
01:28:58He began sifting through that vital one percent of DNA that is different in humans from chimps.
01:29:05NOONAN: It's kind of one of the fundamental questions in science is: What makes us who we are?
01:29:12And that's really what we're trying to get to; what makes humans human.
01:29:18NARRATOR: It was slow work.
01:29:21One percent may not sound like much, but it's still some 30 million of DNA's chemical letters-- A's, T's, C's and G's.
01:29:30NOONAN: The genome's a big place.
01:29:34And just by looking at sequence, you really can't tell, for the most part, what is important and what isn't.
01:29:40NARRATOR: But eventually, in human DNA he spotted something.
01:29:47A sequence that was different in 13 places compared to chimp DNA.
01:30:01The trouble was, he had no idea what this piece of DNA actually did.
01:30:09To find out, he inserted it into the embryo of a mouse.
01:30:15To make the effects of the DNA easier to follow, he attached it to another gene that gives off a blue color.
01:30:23That way he could see where the gene became active in the embryo.
01:30:27As the embryo developed, the piece of DNA seemed to be active all over the place.
01:30:35But most intriguingly, it was doing something in the growing paw.
01:30:45Well, I thought "Wow, this is really cool." It was a really striking image.
01:30:51NARRATOR: What Noonan saw was that the human DNA became active in the mouse embryo's thumb and big toe.
01:31:02It seems that Noonan may have found a switch that helps form that key human attribute: our thumb, the part of our hand that gives us so much power and precision.
01:31:22It's that power and precision that enables us to hold a paintbrush...
01:31:30manipulate tools...
01:31:34pilot a jet fighter, record our thoughts.
01:31:40All those things that separate us from other apes.
01:31:51Of course, having a nimble hand is one thing, but you have to know how to use it.
01:31:58And for that, you need to have humankind's other signature organ: our brain.
01:32:13The human brain is vast, three times bigger than a chimp's, and is structured very differently.
01:32:20How this extraordinary organ evolved is central to understanding why we are the way we are.
01:32:28It is something that Darwin himself was at a loss to explain, which is why many of his critics remained unconvinced by his account of human origins.
01:32:44But now part of the answer to why we have such a remarkable brain may have come from a surprising source.
01:32:53Hansell Stedman is a dedicated athlete and a medical doctor.
01:32:58He never imagined he would come up with an answer to a profound evolutionary mystery.
01:33:04He has devoted his career to trying to cure muscular dystrophy-- a distressing and sometimes fatal degenerative disease.
01:33:16His quest is very personal.
01:33:17STEDMAN: My first exposure to muscular dystrophy was inescapable; my younger and my older brother both bornwith muscular dystrophy.
01:33:27NARRATOR: Muscular dystrophy is a genetic disease.
01:33:31Its sufferers have a mutation in one gene that robs their muscles of the ability to repair themselves.
01:33:39STEDMAN: Typical workout here on the rocks might blow through a few thousand muscle cells, but they'll regenerate overnight and, if anything, be a little stronger the next day I come in as a result of all of that.
01:33:53Whereas in muscular dystrophy, the injury process is greatly accelerated and the injury process outstrips the body's ability to repair.
01:34:05NARRATOR: In search of a cure, Stedman is investigating the hundreds of genes that control the development of muscles.
01:34:15So when the Human Genome Project took off, Stedman seized his chance.
01:34:19STEDMAN: When the horsepower of the entire Human Genome Project kicked in, we knew exactly what to look for.
01:34:27NARRATOR: Stedman was hunting for any new muscle-making genes.
01:34:33And so, as the human genome was sequenced, he began sifting through the vast mountains of data.
01:34:42Eventually he found what he was looking for-- a previously unidentified muscle-making gene.
01:34:51But there was something strange about this new gene.
01:34:54It didn't look like any other muscle-making genes.
01:34:58Two letters were missing.
01:35:01This gene should cause a disease.
01:35:09STEDMAN: It became very clear early on that if you have a mutation of this type, you get some serious muscle problem going on.
01:35:21NARRATOR: Here was a puzzle.
01:35:22Why would humans carry a gene that was clearly damaged?
01:35:26Perhaps it was simply a mistake in the data.
01:35:31Stedman decided to dig a little deeper and look in another human subject.
01:35:39STEDMAN: In the department of true confessions, we do certain experiments first on ourself, largely out of convenience.
01:35:44You can swab your own cheek and get working on some DNA.
01:35:51NARRATOR: To his utter amazement, he found the same damaged gene in himself.
01:35:57I'm seeing this in my own DNA, and it's suggesting that "Wait a minute.
01:36:00"That means there's a muscle disease here somewhere, a muscle disease that I'm unaware of." And I thought it would be worth checking this out in some other members of the lab.
01:36:11NARRATOR: A few swabs later and...
01:36:16STEDMAN: Sure enough, at the end of the day, every single person had the same glitch in their same DNA at the same place.
01:36:27NARRATOR: Here then was a real mystery.
01:36:30It seemed that this particular muscle-making gene was common in humans.
01:36:36But when he identified the same gene in apes, it was just like any other muscle-making gene.
01:36:44Why was there such a difference?
01:36:47What did this gene enable one species to do that the other could not?
01:36:54Stedman began to research the role of this gene in apes.
01:36:59And he found it made one particular kind of muscle-- the muscle for chewing.
01:37:06In fact, the muscle used to close the jaw.
01:37:12In humans, that genetic glitch meant that we chew with just a fraction of the force of an ape.
01:37:19This in itself was interesting, but where Stedman went next was truly intriguing and highly controversial.
01:37:30He drew a direct connection between the power of our jaw muscle and the evolution of the human brain.
01:37:46Stedman's thinking goes like this.
01:37:51The skulls of apes and humans are made of several independent bone plates.
01:37:57They let our heads get bigger as we grow.
01:38:03The muscles for chewing pull against these plates.
01:38:07And in an ape, these forces can be enormous.
01:38:12STEDMAN: In the gorilla, the muscle-- the size of a human thigh muscle-- lives here and has to go through this large space to power the jaw moving back and forth.
01:38:25We're not talking biceps, tricep, we're talking quad here.
01:38:29This is an enormous muscle that has to come right through this hole here to power the jaw-closing apparatus.
01:38:40NARRATOR: Stedman contends that all this muscle power forces an ape's skull plates to fuse together at an early stage, and this puts limits on how much the brain can grow.
01:38:54STEDMAN: In a chimpanzee, gorilla, orangutan, those growth plates arepretty much shut down, closed for business by aboutthree, four years of age.
01:39:06In a human, they remain open for growth to perhaps age 30.
01:39:17NARRATOR: This, Stedman believes, is the key.
01:39:20A mutation in our jaw muscle allows the human skull to keep expanding into adulthood, creating a bigger space for our brain.
01:39:36And so our most important organ is able to grow.
01:39:44It's very cool to us to think that some kind of muscle-altering mutation might have actually been a signature event in the evolution of what makes us distinct as a species.
01:40:02It might have been an absolute prerequisite for us landing where we are today.
01:40:13NARRATOR: But having the space for a big brain is one thing.
01:40:17What is needed to actually grow one?
01:40:27That is the question that Chris Walsh is trying to answer.
01:40:32He's another scientist who never expected to be taking on what even Darwin didn't know.
01:40:37WALSH: I never thought that I'd be studying evolution.
01:40:40I'm a neurologist interested in the brain and kidswith neurological problems.
01:40:45How you doing, buddy? Are you doing all right, huh?
01:40:49You doing okay?
01:40:51No one was more surprised than us to find that the study of kids with disabilities would lead us into these fascinating evolutionary questions.
01:40:59Is his breathing generally okay during the day?
01:41:02Sometimes when he gets startled, it will go up fast, like...
01:41:06(panting) ...but then he calms himself right back down...
01:41:10NARRATOR: Walsh is a specialist in a rare disorder called microcephaly.
01:41:14Children with microcephaly are born with brains that can be half the normal size.
01:41:21WALSH: This disorder can be very devastating for the kids that have it.
01:41:25They typically will have severe mental retardation, and so will not be able to achieve normal language and normal schooling.
01:41:32And so it's really an event that defines the whole family.
01:41:35It defines the lives not only of the child, but of the parents of that child.
01:41:39And these families are desperately eager to try to understand at least what caused the disorder in their kids.
01:41:48NARRATOR: The purpose of Walsh's work was initially to help families that might be carrying any defective genes causing microcephaly to plan their lives.
01:42:00We're able to offer those families predictive testing, so that if they're planning on having additional children, we can tell them ahead of time whether that child is likely to be affected or not.
01:42:13NARRATOR: First Walsh had to decide where to look in the vast genome to find any possible microcephaly-causing genes.
01:42:22So he focused on one particular area of DNA.
01:42:27Other research suggested it contained a gene involved in the condition.
01:42:33That gene is known to control how and when brain cells divide in animals, such as fruit flies and mice.
01:42:41What this gene seems to do is help control the fundamental decision that the brain has to make, which is "When do I stop making cells?
01:42:49When is the brain big enough?" NARRATOR: Then his team began searching for that same gene in a family with a history of the disease.
01:43:00And sure enough, they found something.
01:43:04A gene that helps direct brain growth.
01:43:09And crucially, it was defective.
01:43:14Walsh decided to check this finding in other patients.
01:43:17WALSH: Once we found this gene, we sequenced it in our kids with microcephaly disorder.
01:43:25And we found that one family after another had a disabling change in the gene that completely removed its function.
01:43:33NARRATOR: In total he has found some 21 different mutations responsible for microcephaly.
01:43:42Sometimes one of the DNA's chemical letters is replaced with another letter.
01:43:47Sometimes letters are missing entirely.
01:43:49But whatever the defect is, they all stop the brain cells from dividing at a very early stage of development.
01:44:00Walsh was now certain-- thanks to his microcephaly patients-- he had found a gene key to the growth of the human brain.
01:44:12Now he decided to compare normal versions of the gene found in healthy humans with the same gene in chimpanzees, our closest relatives.
01:44:24And what he found was astonishing.
01:44:31The gene in humans was radically different from that found in chimps.
01:44:39There had been a large series of mutations.
01:44:45It could be that these mutations were a major factor in the evolution of our huge brains.
01:44:54And this discovery came about only because of Walsh's work with his patients.
01:44:59I think one of the amazing things for us was the extent to which studying human disease can unexpectedly enlighten us about something like human evolution.
01:45:16NARRATOR: But this is only the beginning of our understanding of the evolution of the human brain.
01:45:21It's an area of research that is now attracting scientists with a range of skills that Darwin would have marveled at.
01:45:36Katie Pollard is a biostatistician.
01:45:39Her life is spent crunching numbers.
01:45:42POLLARD: What I love about my work is geeking out on a computer and writing programs and thinking about biology.
01:45:49And that in doing this, I'mactually working on something that not just scientists careabout, but really every human being can relate to and cares profoundly about, and that's what makes us human.
01:46:01NARRATOR: Pollard has constructed an ambitious computer program.
01:46:06It's designed to highlight DNA that is similar in apes and other animals, but which is very different in humans.
01:46:15That way, she hopes to identify the key DNA that makes us, us.
01:46:23POLLARD: Out of these 15 million letters that make humans different from chimps, we need to try to figure out which ones were important.
01:46:30And so we use a technique which is to look for places where human is different from chimp, but chimp looks almost identical to the other animals.
01:46:41NARRATOR: She too is looking for DNA relating to the human brain.
01:46:46POLLARD: The brain is one of the things that's changed the most during human evolution, both in terms of its complexity and its size.
01:46:54And so when we look to find the parts or our genome that make us human, we're particularly interested in finding out whether these are things that are involved in the brain.
01:47:06NARRATOR: It is a huge feat of number crunching, as Pollard loaded in DNA sequences from both humans and chimps.
01:47:15POLLARD: You basically take a bunch of computer hard drives and you stack them up together.
01:47:20We were able to take a task that would have run for 35 years on a desktop computer and do it in one afternoon.
01:47:30NARRATOR: And at the end of that afternoon, they had a whole array of material charting the differences between humans and chimps.
01:47:41Importantly, many of those differences were not in the actual genes.
01:47:47They were in switches.
01:47:50POLLARD: It turns out that the vast majority are not genes.
01:47:54Instead they're pieces of our DNA that we can think of as switches-- they're pieces of DNA that turn a nearby gene on or off...
01:48:04that tell it where, in what cells in our body, in what tissue, at what time or at what level to be operating.
01:48:13NARRATOR: And there was something even more intriguing about those switches.
01:48:18A large number of them, more than half, were nearby a gene that was involved in the brain.
01:48:27NARRATOR: In Pollard's work, one particular piece of DNA stood out.
01:48:34It was a piece of DNA that is known to be active in the development of one of the key parts of the human brain in the embryo...
01:48:42the cortex.
01:48:45The cortex is that wrinkled outer layer of our brain.
01:48:51It's vital for those defining human capabilities like language, music and mathematics.
01:49:07When she looked at that DNA in chimps and compared it to the same DNA in a chicken, it was different in just two letters.
01:49:17But in humans it was different by 18 letters.
01:49:23A massive mutation.
01:49:29This was about as great of a eureka moment as you could have as a scientist.
01:49:35NARRATOR: So here is another intriguing piece of evidence suggesting how DNA can shape our distinctive human qualities.
01:49:43We now know that DNA works in many different ways, through genes that make the stuff of our bodies, through switches that turn those genes on and off and through sequences of DNA's chemicals that throw those switches.
01:50:00Taken together, what this all adds up to is a way that we can at last understand how small differences in DNA can generate enormous change.
01:50:12POLLARD: Basically, you can make massive changes just changing those switches.
01:50:17So a small change, a couple of DNA letters, could have a profound effect.
01:50:24NARRATOR: And so that final Darwinian puzzle-- how a human can be so closely related to an ape and yet be so different-- is now slowly being answered.
01:50:44150 years after Darwin first put forward his grand theory to explain the great diversity of life, the scientists who carry on his legacy have advanced his work in wondrous ways.
01:51:02I think if Darwinwere here today, he'd be absolutely stunned, delighted, even moved to see howmuch his theory has grown.
01:51:13TABIN: What we now are able to understand on the one hand would just blow him away.
01:51:18But I also think it would give him enormous satisfaction, because ultimately everything we've been learning validates the things that he said.
01:51:26JUDSON: I think that Darwin was a remarkable scientist and absolutely should be celebrated.
01:51:31However, I do not think that he was the end of evolution.
01:51:36On the contrary, I think he was the beginning.
01:51:37He outlined the major points, but we have discovered more than I think he would have imagined possible.
01:51:47NARRATOR: As we celebrate the 200th birthday of Charles Darwin and the 150th anniversary of his great work, there is still much more to understand about how the endless forms of nature have arisen.
01:52:12And in rising to that challenge, it is likely that we will continue to advance medicine and come to a better understanding of ourselves as well.
01:52:31NOVAhas a brand-new evolution Web site with dozens of videos, interviews, slide shows and the latest in evolutionary science.
01:52:38Bookmark it today and let us know what you think.
01:52:42Find it at pbs.org.
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