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 radioactive monkey which will turn them into a terrifying humanoid battle monkey. Or they want to make a fly with eyeballs on its butt, or like a chicken with fangs.

Most of the time scientists don't get to do that stuff. Like, you may blow something up, but it's either going to be in a like a really controlled setting or it will be on accident, in which case it's bad. Like the lab where I first worked- the first lab I ever worked it- 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 its butt, or even a chicken with teeth. But no battle monkeys! 

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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 can- you can see how we kinda- kinda 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's 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. (Shut up) No I won't shut up. Humans and mice are 85% genetically identical. So why then are mice little and skittery, covered in white fur and have beady little eyes, while I can like walk upright in a non-skittery way, and have beautiful, deep, mysterious eyes?

 

I'll give you the long answer in a minute, but for now, 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're 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.

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But 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 animal's 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 those top tier of regulatory genes there are scads of other genes that act as like subcontractors. Like if the Hox gene tells its 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 tiered 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 McGinnis do they tell each other how to do stuff? Well, since Evo-devo is 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 everyone of our chromosomes- even the sex chromosome. 

Are regulatory genes inherited?- is also still being studied. From what scientists have been able to deduce so far, most regulatory genes are inherited very much 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's 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.

Something that's a 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 when 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 at the very highest tiers, the ones that say like, head here and eye here, not only tend to be the same within a species. They're also very similar across different animal groups, like between all mammals, or even all vertebrates. The differences between my regulatory genes and a mouse's regulatory genes are way down in the chain of command. 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 those general instructions are the same. And that's why 85% of humans' genetic makeup is the same as mice. Mice. Mouse, mice, meeces.

Okay, you've been very patient, my students. So I've got a surprise for you. We're gonna 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, 'cause I want you to guess. 

Wrong! The fruit fly did not grow a mouse eyeball next to its back leg. It grew a fruit fly eye next to its 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 an eye, you'd get a mouse eye on a fruit fly's butt, but instead it told the fruit fly cells, make an 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 frickin' messed up, but also frickin' 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 really revolutionized 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 50% mutation in genes, which would take a long time, and 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 can have huge effects on how an organism is actually assembled. 

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To understand how this works, let's look at why birds don't have teeth. So birds evolved from theropod dinosaurs, which are these freaking sweet dinosaurs, like velociraptors, which look a lot like birds, but you know, 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, then gradually mutated to make less and less and less of each of those things until they made none at all. And 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 dinosaurian 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 have 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 throwback 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. Crazy! I know! It's so cool! I don't... it's just... I... this is.... It's all fairly new science, so this is still, like in my head, it's like really fantasti- fantastinating. That's a word I made up! 

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Thank you for watching this episode of Crash Course Biology. I hope that I blew your mind, or that you learned something, or that you do well on your test, or why ever you came to watch this episode. If you go over there [points to right half of screen] you can click to catch up on things that you may have missed, or just rewatch the whole episode because you gotta emphasize it in your mind. Otherwise, you don't remember these things.

Thanks to everybody who helped put this episode together. 

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Goodbye.