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Male Scientist: When little kids say they want to grow up to be a scientist, here's what they actually mean. They want to blow things up in a laboratory setting. They want to get bitten by a radio active monkey, which will turn them into a terrifying humanoid battle monkey or they want to make a fly with eyeballs on it's butt or like a chicken with fangs. Most of the time scientists don't get to do that stuff. You may blow something up, but it's either going to be in like a really controlled setting or it will be on accident in which case, is bad. Like the lab, where I first worked, the first lab I ever worked in had a blood stain on the ceiling, but if you're a scientist specializing in the amazing new discipline of evolutionary developmental biology you may just get to make a fly with eyeballs on it's butt or even a chicken with teeth, but no battle monkeys. (music) So, evolutionary developmental biology or Evo-devo for all of us cool kids is a new science that looks deep into our genes to figure out how exactly they give instructions to make different parts of our bodies and as the name suggests, it's giving us some hot leads, into the nature of, and mechanisms behind evolution. One big thing it's showing us is that animals, all animals are way more similar than we ever imagined. You know how you always hear about how humans and chimps are 98.6% genetically similar? It kind of makes sense, right? Because chimps and humans, you could see that we kind of, kind of look alike. Like if you walk into a coffee shop and there's a chimp sitting in a chair and it's like maybe wearing a fedora or something, you might briefly mistake that chimp for a human. You might not even notice it sitting there. It could happen, but what about a mouse? You are not going to mistake a mouse for a person. How genetically similar do you think we are with mice? How about 85% similar? Voiceover: Shut up! Male Scientist: No, I won't shut up. Humans and mice are 85% genetically identical. So, why then, are mice like little and skitter-y, covered in white fur and have beady little eyes while I can like walk upright in a non-skitter-y way and have beautiful, deep mysterious eyes? I'll give you the long answer in a minute, but for now, the short answer is, it's all because of the incredibly weird and amazingly powerful genes called developmental regulatory genes. Mostly when we're thinking of genes we think of the things that code for some useful enzyme or protein like the ones that determine what our ankles are going to look like, but those ankle genes don't just come on and off at random. They have to be turned on and off. That's what these developmental regulatory genes do. They activate the genes that put the body parts together. They don't tell them how to do it, mind you. They just tell them when or if it's time to get to work. And since they're the ones pretty much calling the plays, regulatory genes start working rather early in embryonic development. For instance, a kind of regulatory gene called gap genes are responsible for telling the blastula, that little hollow ball of cells that forms during the early stages of development, like, make a mouth here and let's put an anus over on this other end. Probably the most amazing kind of regulatory genes are the homeobox genes or hox genes, which kick into gear after the embryo is more developed. Hox genes literally control the identity of body parts, setting up how an animals body is organized. Like, here's where you put the leg and here's where you put the tail. And like I said, these hox genes don't give instructions for how to create legs and tails. There are a bunch of other genes that are in charge of the actual craftsmanship of the body parts. You can think of the hox genes as like the head architects in the construction of a building. They've got the master plan, but they don't do any of the construction themselves. That's way beneath them. Because under this top-tier of regulatory genes there are scads of other genes that act as like sub-contractors. Like if a hox gene tells it's direct subordinates, "Make an eye here." The subordinates then turn around, activate other regulatory genes to give more specific instructions like, "This is where we got to put the collagen for the outer shell of the eyeball. And make some nerve tissue for a retina right here." Again, these second-tier genes and third-tier and fourth-tier and on down the line don't actually do any of the work. They just send instructions down the chain of command adding more specific information to the instructions as they go. It's a really rigid hierarchy. No gene in your body, aside from that very first one, does anything until it's told when and how much to do it. So, because I know that you're such a sort of intelligent and curious student, I know what you're wondering right now. What activates that first regulatory gene and how in the name of Bill McGuinness did they tell each other to do stuff? Well, since evo-devo was a relatively new discipline we don't really know all the stuff that I wish we knew. That's for you to figure out when you become a biologist. Scientists are starting to think that a lot of the human genome that has, until recently, been considered junk DNA because it apparently doesn't code for anything, might actually be regulatory genes. For instance, just in the past few years, we've learned that humans have about 230 separate hox genes in our genome. And they appear on every one of our chromosomes, even the sex chromosomes. How regulatory genes are inherited is also, still being studied, from what scientists have been able to deduce so far, most regulatory genes are inherited very much in the same way as all of your other genes, but for some really early stage regulatory genes, the proteins that they're coded to produce called gene products, have already been made and are sitting in the egg before it is fertilized, waiting to tell the embryonic cells what to do to get the ball rolling. Another thing that your mom did for you that you probably never thanked her for. So here's the really cool thing, even though most regulatory genes are inherited, each individual within a species, tends to have the exact same DNA sequence in those genes. There aren't even different alleles and if you think about it, they kind of have to be the same since all individuals of a species should be built from the same basic blueprint. Like, you don't want people walking around with thumbs sticking out of their heads. Now, this gets me back to me and my beady eyed friend, the mouse. Hox genes and other regulatory genes that are the very highest tier, the ones that say like, "Head here and eye here." Not only tend to be the same within a species, they are also very similar across different animal groups. Like between all mammals or even all vertebrates. The differences between my regulatory genes and a mouses regulatory genes are way down on the chain of commands where the instructions are the most specific, but the big picture stuff like you're a vertebrate and you have four limbs and you have hair and breast tissue and ear bones and all that stuff that all mammals have, all of those general instructions are the same. And that's why 85% of humans genetic make-up is the same as mice. Mices, mouse, mice, meeces. (piano music) Okay, you've been very patient, my students, so I've got a surprise for you. We're going to make some butt eyeballs. In 1995, in a very cool and also totally messed up experiment, a team of researchers in Switzerland took a hox gene from a mouse embryo, one that said, "Eye goes here." And inserted it into the DNA of a developing fruit fly embryo, but they activated the mouse eyeball gene in a region of the fly that would become the fly's back leg. And so what do you think happened? I'm not going to tell you yet because I want you to guess. Wrong! The fruit fly did not grow a mouse eyeball next to it's back leg. It grew a fruit fly eye next to it's back leg. Remember, the gene didn't say how to make an eye, it just gave the instruction to make an eye. If it had said how to make the eye, you'd get a mouse eye on a fruit fly's butt. Instead, it told the fruit fly cells, "Make and eye here." And those fruit fly cells had their own instructions regulated by another whole set of regulatory genes. And once they got the order to make the eye, they made it the only way they knew how. That is pretty fricken' messed up, but also fricken' awesome. Now, in addition to getting me in touch with my inner mentally unstable, child scientist, this kind of experiment is where evo-devo has begun to really revolutionize our understanding of evolution. Because we've known that evolution can take place over a really long time, but we haven't really been able to figure out how it sometimes happens really fast. Traditionally one of the main ways that scientists have explained evolution is through genetic mutations, but an organism would have to do a lot of mutating to evolve from say, a dinosaur into a bird. It used to be thought that a 50% change in form would require a 50% mutation in genes, which would take a long time. Way longer than the pace at which we see things actually evolving, but it turns out that a small change in a regulatory gene up at the top of the chain of command could have huge effects on how an organism is actually assembled. To understand how this works lets look at why birds don't have teeth. So birds evolve from theropod dinosaurs, which are these fricken' sweet dinosaurs like Velociraptors, which look a lot like birds, but way more awesome and with big razor sharp teeth, but you may have noticed that birds don't have razor sharp teeth, they have beaks. Under the old way of thinking about evolution, the loss of the teeth would have had to happen very slowly as the genes make enamel and dentin and gradually mutate it to make less and less and less of each of those things until they made none at all. For a long time, that's just how we thought dinosaurs evolved into birds, but there was one problem. It would have taken way longer for all of those mutations to occur than it actually took for dinosaurs to evolve into birds based on the fossil record. Fortunately, evo-devo is offering us an explanation. A single mutation in the regulatory genes could have shut off the enamel and dentin production and another mutation in another regulatory gene could have upped the keratin production from the level of 'make some scales' to the level of 'make a beak'. So birds actually do still have genes for teeth from their dinosaur-ian ancestors, they're just not expressed because the regulators don't turn them on, but how do we know that? Well, in 2006 a biologist at the University of Wisconsin named John Fallon who studies birth defects was looking at some mutant chicken embryos and noticed that they had formed little teeth, like little baby reptile teeth. It turns out that the mutations affected the chickens gene regulation, allowing the teeth, a feature lost to birds around 60 million years ago, to just pop back up again. The same sort of crazy throw back features have been observed in snakes born with legs like their ancestors once had or blind cave fish, suddenly born with eyes. If you turn those genes back on, those ancient repressed features come back. It's crazy! I know! It's so cool! I don't ... I just ... this is ... It's all fairly new science, so this is still like in my head it's like really fantascinating ... That's a word I made up!