Kind: captions
Language: en
We have to give credit where credit is
due. And and the big
>> catalyst for understanding development
is the fruit fly.
>> The fruit it's always the fruit fly in
the mouth. Yeah. Well, let me tell you
the fruitfly, baby paid my mortgage.
Okay. So, that's why we got to credit
where credit's due. A fruitly what
what's the advantage of the fruitfly?
Very short life cycle, just a couple
weeks or so.
>> Uh you can keep a lot of them in a small
amount of space and they're cheap to
keep, but they are complex animals,
right? So, you start you have a little
tiny animal like that. It builds all
these kind of tissues, right? It's got
wings. It's got limbs. It's got a little
heart, right? It's got a brain. It's got
eyes. So, we can watch we can watch the
development of these creatures and we
can change what's happening development.
>> So, let me So, I'm assuming it's
happening in like a a egg pupa type
transition.
>> Egg larva pupa adult. Yeah.
>> So, are you
like scanning the larvae and
>> Sure. We can looking at the inside. We
can put them we can put all those stages
under microscopes and see what's
happening.
>> But what gave us power was
>> genetic approach to it. So what a
genetic approach is we deliberately
induced mutations in fruit flies and
started studying the interesting flies
that would come out. So some like one of
the most famous fruit flies was fruit
flies that instead of antenna have legs
on their head.
>> Oh geez. Yeah.
>> That doesn't sound very useful. No, but
it's a it's a laboratory mutant except
for as incredibly useful as a laboratory
mutant because those are fully formed
legs in the place of antenna and you
start thinking how do you put legs in
the place of antenna
>> and then you map where those mutations
are and it goes to a single gene
>> and that gene turns out to be a gene
that orchestrates a big part of the
>> So let's talk process. Is it the case
you blindly
>> ch make a ch genetic change you see what
the outcome is and then you go back and
look at the genome
>> bingo. Exactly. And you're you're
picking those flies that are
interesting, right? You're saying, uh,
well, maybe I have a fly that changes
eye color. I go map where that happened.
But in this case, I find change a take a
fly that has legs on the top of his
head. And I say, what happened?
>> So, let me let me ask you a question
there. So, in in in astronomy, Yeah.
>> which I know a lot more about. Yeah.
>> One of the ways that uh you discover
exploding stars and moving objects like
asteroids is you do an image
subtraction. Yeah. And what you know
everything that remained the same
disappears and the only thing that
remains is what changed. Yeah. Right. Is
it like that with DNA?
>> It's logically it's very similar to
that.
>> Okay.
>> To a geneticist it will map the mutation
because it can it can figure out where
in the genome the change has happened.
And you can do that at sort of a low
level of resolution sort of chromosomeal
level and say I think it's in this part
of the chromosome. Now with DNA
sequencing tools we can just sequence
the animal and go there it is right
there. That's the change. the parent
didn't have it.
>> Wait, that's that's easy for you to say,
man. When I look at images of these DNA
sequences, I just see like barcodes, you
know? I just see dots.
>> Yeah. Well, we need help with computers
to to sift through all that DNA. But
yeah, we can now pinpoint mutations just
sequencing DNA. If you take an animal
that that doesn't have the change, that
has antenna in the right place
>> and the animal that has the legs on top
of its head, you can see the difference.
Bang. Okay. Couldn't do it in 1983 when
I got into the game.
>> Got it.
>> Didn't have those tools. we we've got
those tools now.
>> So, it was a it was a longer march to to
discovery in those days, right? But
those discoveries, what were really
important is it taught us that
>> there was a small subset of genes. So,
the fruitfly has maybe 14,000 genes,
something like that. There was a small
subset of genes that kind of
orchestrated development, had a really
outsized impact on development. And if
you messed up one of those genes, weird
things happen. Like there were genes
that you'd wind up with half the number
of segments. So, you know, if you've
looked at insects, you've also looked
at, you know, a lobster on a plate,
whatever it is, it's segmented, right?
It's got uh some segments of the thorax,
it's got segments of its abdomen. So,
there are genes that in the fruit fly,
you mess them up, it comes up with half
the number of segments, right?
>> Or there are genes, you mess them up, it
has no eyes.
>> Oh, wow.
>> Right. So, you got a you got an eyeless
fly, an adult, a fly with no eyes,
>> right?
>> Well, why was that helpful? Well, we map
the gene for eyeless. It tells us a gene
is necessary to make an eye.
>> And this is a different trajectory we're
this conversation is going to go on. And
then you know what blew our minds?
Humans have that same gene. And when you
mutate in humans, we don't have eyes.
>> What? That's what I was going to ask.
Does it translate to other species?
>> Yeah. And no one expected that.
>> So that means that the eye making gene
preceded the split.
>> That's right. Exactly. That's the
correct inference, right? And that blue.
No one expected that. You think of a
fruit light, fruitfly anatomy, human
anatomy. Look, I was I had a PhD. I was
going off to do this work and my mentor
said, "You work on fruit flies, you're
walking off the edge of the earth
because nothing you're going to find has
anything to do with making furry animals
like us."
>> Yeah,
>> that was the bias that existed across
the world.
>> And then, you know, a little small group
of people studying fruit flies like,
"Hey, look at this gene. Hey, look, you
got it, too. We got it, too. Oh my gosh,
mess that up.
>> We don't have eyes either." So what
about limbs? Right. So like the legs on
the head. So fish have fins.
>> Yeah.
>> Arthropods have limbs. So they have some
common ancestor for which the limb gene
exists that you could manipulate.
>> Exactly. Actually uh shown in my lab
that that common limb bearing. Yeah.
>> I came too late to to get a
>> you could Yeah. 1997. You got if you got
to my lab in 96, you would have done it.
again surprised us because the dogma at
the time was these limbs were all
independently invented, right? Cuz a fly
walking leg is a hollow structure it's
walking around on and you know and our
limbs are got bone in the center and all
that kind of stuff.
>> But essentially as appendages that stick
out from the main body.
>> Yeah.
>> Those instructions go all the way back
500 million years
>> and these are just unfolding differently
in in you and I from a fruitfly. So the
fruitly was a passport to the whole
animal kingdom. Wow.
>> Nobody saw it coming. But I'm smiling
because
>> I took the leap
>> and like as I said, it has paid off
[laughter] handsomely.
>> But it also besides now allowing us to
study development and all sorts of
creatures, it allowed us to study
evolution because then we find these
bodybuilding and body patterning genes.
Again, it's a small subset of genes that
are sort of devoted to that. A lot of
genes, they just kind of run the
physiology of normal cells, but there
are genes devoted to sort of sculpting
the body. They affect the number, the
size, the shape, the color of body
parts. And that's the stuff that's
really interesting in evolution. So then
we started studying things that look
different, either
>> insects versus other kinds of arthropods
or maybe just like, you know,
butterflies versus fruit flies. How do
you get, you know, spotted wings and
things like this? All right.
>> And then we're starting to figure out,
>> oh, how do you make something new?
>> And the general rule, I'll just give you
the breakthrough. The general rule is
that basically you take old genes and
you use them in new ways.
>> Okay. Okay.
>> Isn't that a simple statement?
>> That's a very God. If I had known that
new creation, if I had known that, I
could have gone to Wall Street and
skipped my whole career in biology. But
it turns out [laughter]
>> good.
>> It was a much better journey. But yeah,
so these and this is also telling us why
these genes have been preserved for
hundreds and hundreds of millions of
years is they get used in new ways in
different creatures.
>> Speaking of which, you know, we we we
mentioned how we found this evidence of
Neanderthal DNA in humans and Denise.
>> Yeah.
>> DNA in humans, but we have even more
viral DNA in our cells, right? So is
that a result of viral infections
happening in the animal across its
evolution or was it all early?
>> Oh no no this is keeps it keeps
happening. Yeah yeah yeah yeah yeah. So
um yeah we we'll see these viral these
vestigages essentially of of viruses
spreading through DNA. We see this in
all sorts of lines of of evolution and
it and it can happen a new all over the
all over.
>> Well, it first came to my attention when
there was a recent um mention of a
discovery that the sheath of our nerves
which allows fast long range nerve
signal transmission was inherited from a
virus. So talking about
>> I don't see how a virus needs that.
>> Yeah. [laughter] Yeah. But we hijack
that genetic information and and
repurpose it in a new way. Yeah. And
this is this is what I mean this sort of
repurposing this sort of co-option. So
we might take you know animal
bodybuilding genes and use them in a new
way. And that's in fact how a butterfly
puts spots on its wings. That's how have
you seen beetles with really big horns?
Yes.
>> Okay. They've taken limb building genes
and they're putting them out on and
they're activating them on their head
and making these appendage like things
on their horns as examples. But we also
we hijack that that viral material and
we use it um for for it's it's just
material to be used and reused.
>> What about spots and stripes? Stripes
and spots. What what was that
originally?
>> Well, spots the the spot making program
in a butterfly actually uses a little
bit of the limb building program, but it
turns it on really late. Okay. So, if
you're just building if you've got the
embryo and it's just really an insect
embryo, they often would look like
little mini footballs. Okay. and you
know like a little bit of an oval,
right? Without any uh you know shape or
form, you know, no no specific tissues,
whatever. You activate well you activate
the limb program then you build limbs
and you build the basic limbs of that
body. But days and weeks later when you
have the pupa and you've already made
limbs, you've already made the wing.
Turn that limb building program on in
the wing. Connect it to the pigmentation
program. Okay? See, you make a new
connection
>> and you build a pattern of spots.
>> That's a whole new realm. you just
introduced into this conversation. It's
not just turning genes on and off. Now
you can connect them.
>> You can connect them. Right? So there's
this whole I'll kind of sort of say the
software which is how the genes are
connected in development. And it's those
changing of connections that's a big
part of the evolution of anatomy. Okay.
So you could take the same I I'll just
give you this thought experiment. Take
14,000 genes and I think I can build a
fruitly, a lobster, a crab, a dragonfly,
and a butterfly out of those same 14,000
genes. I don't need any new genes. All I
have to do is just keep change their
wiring.
>> What?
>> That's the big discovery. That's the big
discovery. Yeah.
>> Holy cow.
>> It's not the genes you have, it's how
you use them. And how you use them is
these connections between the genes.
>> So the genes are like Lego bricks.
That's right.
>> You can build different animals.
>> You can build different animals out of
the same genes. Yeah.
>> Wow. Yeah. Yeah. And then we see that
that toolkit
>> a lot of homework. All right.
>> I just got a lot of thinking to do now.
>> All right. Pretty,
>> but hopefully it's a little anchored.
It's a little anchored. But then you
say, "Okay, I need to know more."
>> That tool kit's been preserved through
500 million years. We've got it.
Earthworms have it. Elephants have it.
That same
Well, they've got the same They got the
number varies. We probably got 20,000.
So it wouldn't be the case that if you
look at species that evolve later, they
would have the, you know, so there's a
sort of core set and then you add
>> or so there's a core bodybuilding set.
>> Yeah.
>> There's a core kind of physiology set
that just has to run to run cellular
metabolism. That's probably I don't I'm
going to say five six thousand genes
that just to just to do what every cell
needs to do. Couple thou in us a couple
thousand bodybuilding and body
patterning genes. uh and then the rest
may be you know like we got a like we
have genes for immunity big number of
genes involved in immunity adaptive
immunity to to deal with infections so
there are inventions that have come
along our immune system is far more
sophisticated than what you find in
animals without backbones for example
>> um where
a lot of mammals I said are good good at
smelling so are insects they got a lot
of the same smell receptors and stuff
like that so you see expansions and
contractions in some of these
capabilities as lifestyle change. But
there's sort of a core bodybuilding and
a core set of
>> uh cell physiology genes that you'll
just find across the whole animal
kingdom.