JANE PICKERING: Good
evening, everyone.
Welcome on this
wonderfully-- well,
it feels like an
incredibly warm evening,
even though I'm sure
it's only in the 40s,
but somehow it seems
so much better.
I can see a lot of people.
There are seats in the middle.
If people either want to
shunt in a little or just
ask people because there
are definitely seats.
So you shouldn't need to stand.
So, hopefully, people can
shunt along and make room
for everybody.
My name is Jane Pickering.
I'm the executive director of
the Harvard Museums of Science
and Culture, which
includes the Harvard
Museum of Natural
History which is
the sponsoring museum for
tonight's event, which
I'm very much
looking forward to.
We're going to hear from
Hopi Hoekstra, our own Hopi
Hoekstra who's at the
Museum of Comparative
Zoology-- an
evolutionarily geneticist.
And I think it's going to
be a wonderful occasion.
I would like to just say a
couple of housekeeping things.
First is-- and those of
you who come frequently
have heard me say
it many times--
we do have a Spring
program, which
I've forgotten to bring with
me but is actually on a table
to my right.
And that includes a complete
schedule of all our events.
And in two weeks'
time, we actually
have Steve Stearns from Yale.
He's coming on April 17 to give
the final one of this series
of lectures which is the
Evolution Matters Series.
This is the third one.
And I would like to take
a moment to thank Drs.
Herman and Joan Suit,
sitting in the audience,
who sponsor the
Evolutions Matters Series.
[APPLAUSE]
And they have been
dedicated sponsors
of this series
for several years.
And we all know, many
of us in this room
know how important it is
to talk about evolution
by natural selection
in a public forum.
So we're very grateful.
Thank you very much.
You will have also noticed
a new survey on your chairs.
And I know some
people have already
filled it out and handed it in.
So if you haven't, I
encourage you to do so.
It's to enable us to
try and really produce
public programs that are
going to meet everyone's needs
and make them better.
I'd also like to remind
everyone that we do actually
have a special session at the
end of the lecture with one
of Hopi's students, Emily Jacobs
Palmer, on the front row here.
And she's doing a special
session for teachers,
K through 12 or K
through 16 teachers,
about the topic of
tonight's lecture.
I think there may be a
glass of wine involved.
So for those of you who
have signed up already, then
they'll be meeting just
behind the wall here.
So you can either come up
the stairs through here
or go back out of that
door and round behind.
And if there are any teachers
here who didn't sign up,
please know you're
very welcome to come.
So there's always extra spaces.
So if you didn't sign up
but would like to attend,
then please do so.
I am going to stop talking now.
And I'm delighted to
introduce Jim Hanken who
will be presenting our speaker.
And Jim is the Alexander
Agassiz Professor of Zoology
and director of the Museum
of Comparative Zoology
here at Harvard.
And he's also the
curator of herpetology,
and he is also a
professor of biology
in the Department of Organismic
and Evolutionary Biology.
Harvard gives professors
a lot of names,
and I think Jim has
some of the most.
He is a principal investigator
at the Hanken Laboratory,
where his team studies the
evolution of morphology,
developmental biology,
and systematics
with a special
emphasis on amphibians.
So I'd like to bring
Jim up to the stage.
Thank you.
[APPLAUSE]
JAMES HANKEN: Thank you, Jane.
And good evening, everyone.
I actually have one
additional announcement
which is to ask those if
you have your cell phones,
please turn off the ring.
I have the distinct honor of
introducing tonight's speaker.
And I'd like to do so by telling
you that it's a great time
today to be an evolutionary
and comparative biologist.
Not only do we continue
to discover and document
previously unknown biodiversity,
new species, and the like,
but a series of
technological breakthroughs
in molecular biology,
genetics, computer science,
digital imaging, and other areas
allow contemporary biologists
to answer, at long last,
many fundamental questions
regarding the evolution and
diversification of organisms
that practitioners of our
craft have been asking ever
since Darwin and,
indeed, even before then
but were unable to
resolve satisfactorily.
In this respect, I can't
think of a better person
to illustrate the potential,
the power, and the discoveries
of contemporary biology than
tonight's speaker, Dr. Hopi
Hoekstra.
Hopi is Alexander
Agassiz Professor
of Zoology in the Museum of
Comparative Zoology, where
she also serves very ably
as the curator of mammals.
In addition, she holds
faculty appointments
in the Department of Organismic
and Evolutionary Biology
and the Department of
Molecular and Cellular Biology.
Hopi came to Harvard in
2007 from a faculty position
at UC San Diego, having earlier
completed a bachelor's degree
in Integrative Biology
at UC Berkeley,
a PhD in Zoology at the
University of Washington,
and a postdoctoral fellowship
at the University of Arizona.
She has received numerous
prestigious awards
and appointments.
Perhaps the most recent is
her appointment effective just
this past January as a Howard
Hughes Medical Institute
investigator.
I have a strong suspicion that
Hopi is one of the few HHMI
investigators who maintains
an active field program.
And I'm virtually certain
that she is their only museum
curator.
The Hoekstra Lab uses wild
and laboratory populations
of rodents to study
the molecular, genetic,
and developmental basis
of evolutionary change.
Their work has been featured
widely in the popular press,
including The New York Times,
Nature Magazine, Science
Magazine, National Geographic,
and National Public Radio.
Surprisingly, none
of those articles
discloses what I find
to be one of Hopi's most
remarkable accomplishments.
She is the only biologist
I know who has personally
taken the rectal temperature
of a grizzly bear.
I urge you to ask her about this
during the question-and-answer
session which will
follow her talk.
Ladies and gentlemen, please
welcome Professor Hopi Hoekstra
who will now lead us
from Darwin to DNA.
[APPLAUSE]
HOPI HOEKSTRA: Great.
Thank you for that
introduction, I think.
Always nervous when
Jim introduces me.
It's a great pleasure to be
here to talk on my home court.
It's great to see so many faces,
both old friends and new ones.
So today, what I want to
do is tell you a little bit
about what my lab has been doing
over the last 10 years or so.
So as Jim alluded to,
much of the work in my lab
has been focused
on trying to make
the connection between
genes and traits,
and in particular
traits that are
important for the
fitness of organisms--
that is, our survival and
reproduction in the wild.
Now, most of our
early work focused
on morphological traits, and
in particular camouflaging
coloration, which is nicely
illustrated by this image here.
So this wonderfully adorable
little beach mouse actually
lives on this Gulf
Coast of Florida.
And as you can see
from this image,
its coat nicely matches
or camouflages it
in its natural habitats.
But in recent years, we've
extended that approach
to try to make the link
between genes and behavior.
And the behavior I'm
going to tell you
about today is also
illustrated in this image,
and that is burrowing behavior.
This mouse is emerging from
its freshly excavated burrow.
So as Jim mentioned, I'm
an evolutionary biologist.
So it's hard for me to begin a
talk without mentioning Darwin.
Since a young age, Darwin
was fascinated with beetles.
And he had an early hobby, and
that was collecting beetles,
which quickly
became an obsession.
So he became, especially
in his college days,
very competitive
with his classmates,
including this one who did this
now-famous image, Albert Way.
And they would
compete as how many
beetles they collect
and diversity
in terms of their taxonomy.
But it was clear
from Darwin's notes
that he wasn't just
interested in its taxonomy
or the morphology or size
and shape of these beetles,
but he was absolutely
fascinated with their behavior
and, in fact, kept copious
notes on animal behavior.
And this was one of
the favorite subjects
of his correspondence
in his letters.
So here is an example
of one of the letters,
but the drawing was done
by one of his sisters.
But not only was Darwin
fascinated by behavior,
he was also slightly
troubled by it.
So if you look at The Origin
of Species, in chapter 7,
he addresses the question,
can instincts or behaviors,
instinctual behaviors,
be acquired and modified
through natural
selection the same way,
as he argued, that
morphological traits work?
And he worried that if he
couldn't explain how behaviors
evolve, this would be a
difficulty sufficient enough
to overthrow his whole theory.
Well, in the same
way, he eloquently
argued that morphological
traits could
evolve by natural selection.
Through observation
and experiments
and beautifully outlined
arguments with Victorian prose,
he concluded at the
end of this chapter
that just morphological traits,
behaviors could evolve as well.
Now, of course,
since Darwin, there's
been a large number
of studies documenting
the evolution of behavior.
And there are
behavioral ecologists
who have amassed a large amount
of data that support Darwin's
conclusion that
behaviors can evolve,
and largely, in the same way.
So these things, we have
a field of researchers,
who I would call
behavioral ecologists, who
tend to study a wide
diversity of organisms.
They tend to study
these organisms who
display these
fantastic behaviors
in their natural environments
and tend to focus on questions
at the ultimate level-- how
and why these behaviors evolve.
But there's also another
group of biologists
who study behaviors in a way
that Darwin couldn't even
imagine.
And I'll classify these
folks as neurobiologists
and geneticists.
But their approach is
very distinct yet largely
complimentary to behavioral
ecology in the sense
that neurobiologists
and geneticists
tend to study or focus on a
handful of model organisms,
ranging from laboratory mice to
fruit flies to nematode worms.
They study these model organisms
in controlled laboratory
environments for
very good reasons.
And the questions are largely
fundamentally different--
that is, they're more
interested in the genetic nuts
and bolts of how these changes
at the genetic and molecular
level actually produce variation
in the behaviors we observe.
Now, it's this sort of contrast
that sparked my colleague
and friend Ed Wilson
to famously complain
that the study of behavior
was largely fractionated--
that these two
worlds were ongoing
but never really interactive.
And in some ways, that's why
this is such an exciting time
to be a behavioral
biologist because I think
that these traditional fields
are starting to disappear.
And now, there's a lot of
crosstalk between these two
fields which enables us
to work at the interface
and use approaches from both
of these types of fields.
And this is really
where the work
that we're doing
in our lab rests--
that is, we're
trying to understand
the molecular basis or the genes
or, in fact, the precise DNA
base pair changes that give
rise to increases in fitness.
Again, that affects the
ability of these organisms
to survive, to
reproduce in the wild.
And once we're able to make
this connection between genes
and behavior, I think this
is where we can really
start to address some
fundamental questions
in the field.
This is not meant to
be a complete list,
but I just want to give you a
sense of the types of questions
that we're interested
in addressing.
So, for example, this
is an age-old question,
what are the relative
contributions
of genetic and
environmental effects
to behavioral differences that
we observe not just in the lab,
but that we observe in nature?
And if there is a
genetic component, what
are, in fact, the precise
DNA base pair changes?
What kinds of genes
influence behavior?
And it's not just that we want
to know what the genes are.
We want to know
how they work, how
they work through
our neural circuitry
to actually produce
variation in behavior.
So to address these
questions, what
I see as a fundamental
challenge in biology
is to make the
connection between genes,
neural circuits, and behavior.
So this is going to be the
subject of today's lecture.
But one could argue that if
these questions, again, are not
new, why don't we
already have lots
of examples of genes
that affect behavior?
This is clearly an
interesting subject.
Well, it turns out that
this is really hard.
And it's hard for a
number of reasons.
So just to contrast to earlier
studies in our lab group
where we're looking at
pigmentation differences,
behavior relative
to morphology, we
tend to think of the behaviors
as having lower heritability.
In other words, the
genetic component
may be a little bit smaller.
And that's because,
unlike, let's say,
a pigmentation trait,
a lot of behaviors
can have a learned component,
or they could be transmitted
culturally from
generation to generation
without any changes
in the DNA at all.
There can also be a major
environmental effect, not just
the environment at the time in
which a particular organism is
performing a behavior, but
it could be even earlier
on in their sort of
"childhood" or "mousehood."
Some sort of
environmental experiences
can affect their adult behavior.
And we tend to just intuitively
think of behaviors maybe
being more genetically complex.
We think of behavior as
being a complex trait.
So maybe what we're
looking for is not
genes that have big
effects on behaviors,
but maybe many genes that each
together have a small effect
but then can produce such
a large changing behavior.
And then there's the
problem of tractability.
So if we want to do this not
just in laboratory models,
but we want to extend
it to organisms
that do cool behaviors
out in the wild,
we have to think about
things like tractability.
So you were interested in
elephant behavior, for example,
you might have a problem
with sample size.
But, of course, some things
like having molecular resources
like a genome
sequence, that problem
is becoming minimized
in these days.
But I would argue
the biggest challenge
to studying behavior
or, at least,
a big one is the simple fact
that it's hard to measure.
So we could take
a mouse that has
dark pigment and a mouse
that has white pigment.
And there are lots of
very straightforward ways
to quantify those differences
in that morphological trait.
But if we think about
behavior, one just
has to turn to what is
arguably one of the most
stereotyped and
well-studied behaviors.
And that is the
behavior of Drosophila--
these beautiful
Drosophila fruit flies.
And that is their
mating behavior.
So you'll right away be able
to tell another Drosophila
geneticist that this is how
I understand their mating
ritual to go.
So a male and a female
orient towards each other.
There's a lot of
tapping involved.
The male does some waving
of its wings and singing.
There's some licking, in fact.
All of that happens
even before there's
an attempt at copulation.
So you just have to
try to now think about
if you were going
to try to quantify
these differences between
maybe it's two individuals,
maybe it's two
different species,
is it the angle at
which they orient?
Is it how many times they tap?
Is it how vigorous that
male shakes its wings?
How do you quantify
the differences
in a reliable, repeatable way?
And which differences
actually matter
in terms of the ultimate
reproductive success?
So one thing that
we were trying to do
is to try to circumvent this
problem of measuring behavior.
So we used a little trick.
And that is, we've taken
this idea from somebody
that many of you probably
know and have heard of,
and that is Richard Dawkins,
who maybe in his second most
famous book, The Extended
Phenotype-- it was written
in 1989-- he put forth this
idea of the extended phenotype.
And the idea of the
extended phenotype
is actually one
that's quite simple.
And that is, if genes
control a behavior
and that behavior actually
produces an artifact--
and I'll give you some
examples in a minute-- just
like any other
phenotypic product,
so for example, the
length of our femur,
the color of our hair, we
can dissect that genetically.
So let me give you some
examples of extended phenotypes
just to bring this idea to life.
So one of my favorite
is the bowers
that are built by
Australian bowerbirds.
These bowers are made in a
characteristic size and shape,
decorated in a
characteristic way.
This particular
male bowerbird is
building this bower in which
he'll walk back and forth then
to attract a female.
This particular species
tends to decorate this bower
with blue stuff that it
finds in the environment.
But what's really interesting is
that the size and shape of this
is very stereotyped
within the species
but can vary dramatically
between species,
both in the material
used, how it's decorated,
and the shape of the bower.
The same can be said for
the nest of swallows.
The material that's used,
the location of these swallow
nests, and the size and
shape of these nests
can vary dramatically
between species.
And the same can be
said for spiderwebs.
And then this fourth
example is one
that's a little
bit more complex.
It's a mound of a termite.
It's more complex in
the sense it's not
built by a single individual
but a whole colony.
So the idea is that if
genes control the behaviors
that result in the production
of a bower, for example,
of a certain size and shape
and decorated in a certain way,
then we can treat this bower
just like we would treat
the length of a mouse's
tail in terms of a trait
to then look at genetically.
And in doing so, we can
circumvent the issue
of trying to measure the
behavior itself because now
what we have is the
morphological output
of behavior.
So I'm going to use this idea
of the extended phenotype
to tell you a story about
connecting genes to behavior.
So there are lots of examples
of extended phenotype.
The one that we have chosen to
focus on is burrowing behavior.
Now, burrows are produced by
a wide range of organisms.
Here, I'm just showing you
a few examples of species
that burrow and then the, more
or less, realistic depictions
of those burrows that they make.
But you can see
things from bivalves
all the way up to
these complex burrows
that are built by prairie dogs.
All of these species
have independently
evolved burrowing behavior.
And because it's
occurred repeatedly
over evolutionary
time, that suggests
or is indicative of it having
a function or functional
significance.
So why could burrows
be important?
So we can all think of examples.
For example, they can be
important to avoid predators.
They can be important in
terms of thermal regulation,
either protection from
the cold or from the heat.
For those species that
meet and mate underground,
they can be important
for social interactions.
They could be used for
food storage and growth.
So clearly, burrows can
be important for survival
and then, ultimately,
reproduction.
But the other reason we
decided to study burrowing
is because of an
elegant set of studies
that was done by a
colleague, Carol Lynch
at the University
of Colorado, where
she used laboratory mice,
where she could control
the genetics of these mice,
and did these experiments
in controlled
laboratory conditions.
So what she would do
is take the lab mice,
put them in these large
boxes filled with dirt,
and let them burrow.
This is a particular burrow that
has one entrance as indicated
by that circle.
And the outline of the burrow
is shown in the dashed line.
And what she was able to
show is that some components
of the burrowing of
these particular mice
seem to be controlled by genes.
So here we had two things
that we were interested in,
some ecological
significance, and a hint
that maybe genes were
involved in burrowing.
And just as a side note, because
I think this is a fun fact,
burrows are one of
the few behaviors
that are actually fossilized.
So this is the classic
corkscrew-shaped burrow
built by a now-extinct
giant beaver.
This particular specimen
comes from South Dakota.
But there's some hope
that, potentially, we
can even go back in
time using fossils.
So now that we picked
an extended phenotype,
the next thing we wanted to
do was choose a study species.
We're not studying giant extinct
beavers, I'm sorry to say.
But we've chosen to focus on
this particularly adorable
group of-- I would like to call
them "charismatic mini fauna."
These are the most abundant
mammals in North America.
I think some of you are
probably very familiar with them
because they do invade houses,
especially in rural areas.
But these are Peromyscus mice.
That's the genus.
They're called deer
mice, commonly.
And while, to many of you, these
may look like a typical mouse,
they're in fact
actually quite diverged
from a mouse and a rat
or laboratory models.
So even though they are about
the size of a laboratory
mouse-- and I've actually
brought one to show you--
they are actually
outside of this split.
So they are about 25
million years diverged
from rat and mouse.
And these two are
about 10 million years.
So like laboratory mice, we
can bring them into captivity.
We can breed them in controlled
laboratory environments
and do controlled tests
on their behavior.
And like laboratory mice,
our group and others
are building a whole set of
molecular genetic resources.
So, for example, you have a
genome sequence for these mice.
But importantly,
unlike laboratory mice,
in general, these mice
are not commensal.
And they're really found through
a wide range of habitats.
So we could go out probably just
a mile away from campus, maybe
even on campus, set some traps,
and we would get Peromyscus.
But really, you could go
to the top of the Rockies,
the Coast of Maine,
the Catalina Islands
off the coast of
California, and you'd always
be able to catch
some Peromyscus.
And because they live in
desert environments and forests
and so forth, there's
a lot of opportunity
for local adaptation.
In other words, there's a lot
of both genetic and phenotypic
diversity among
these populations.
There about 55 species
of this particular mice,
but we're focusing
on one of them,
and that is this one here
called Peromyscus polionotus.
Peromyscus polionotus is often
called the oldfield mouse
because it occupies old fields.
So very clever naming.
But they do really stick to
this characteristic habitat that
is open habitat, like
these two images.
And once there's secondary
growth that comes in,
you will not find these mice.
So our field sites include these
beautiful white sand beaches
off the Coast of Florida, which
is no accident we chose that.
The best time to go
is around February.
But some of our field
sites, I have to admit,
are a little bit less glamorous.
This is a burnt peanut
field in Alabama,
where we also
captured these mice.
And the reason that we focused
on this particular species
is because of this fellow here.
This is Francis Sumner, the
classic natural historian.
He was associated with the
Natural History Museum,
in fact, its curator.
He's shown here--
this is a picture
from the 1920s-- in
his field regalia.
I have to admit we do
not dress as nicely
now in the field or elsewhere.
But you can see
his dapper attire.
And Francis Sumner
really is the father
of Peromyscus
biology in the sense
that he spent a vast
majority of his career
driving around the US,
catching mice, and in
particular catching mice
and describing variation
in their morphology,
like pigmentation,
but also some behaviors.
And, really, if you go back and
read the papers from the 1920s,
he's asking the same
questions we are today.
What's the genetic basis of
this variation that we see?
How is it generated?
How is it maintained?
But, of course, he wasn't
armed with the molecular tools
that we are today.
So in particular, he had a
paper that he published in 1929
with his field assistant that
described what I would say
is a very unique
burrowing behavior
of this particular species.
And that is, their burrows
look something like this.
So the burrows are
characterized by this open hole,
a long entrance tunnel,
a nest chamber, and then
a secondary tunnel that
radiates out near the surface,
but importantly, doesn't
penetrate the surface.
You can find these
burrows out in the wild
because you can find this hole.
And if it's an active
burrow, there'll
be this plume of freshly
excavated soil that
indicates the mouse is
actively burrowing in there.
So next, what I want
to do is tell you
a little bit about how we
catch these mice in the field
to illustrate two important
points about these burrows.
So here's one of these open
fields in Florida in February.
And here's a hole
that we identified,
this plume of freshly
excavated soil.
So we found our active burrow.
The next thing we do is
we get a graduate student
to lie down in the dirt, face
first, head near the hole.
And what this particular
graduate student is doing
is taking some plastic
tubing and weaving it down
that hole till he
hits the nest chamber.
And once he hits
the nest chamber,
he blows into that
tubing and agitates
the mice that are in there.
And while we look like
we're standing around,
cheering him on,
we have a purpose.
And that is, the mice are
going to come jumping out
of that secondary tunnel.
We jump on them, with
the ultimate goal
of catching that mouse
or mice that come out.
And so this little story is
to illustrate two things.
First, that secondary
tunnel that I pointed out
is, in fact, used
as an escape hatch.
That is, even though we
can't see the hole-- remember
I told you that secondary tunnel
comes up towards the surface
but we don't see it.
In fact, if we can see
the secondary hole,
we never find the
mouse in that burrow.
They seem to abandon it.
So we have this
secondary tunnel.
And then, secondly, the size
and shape of these burrows
are so stereotyped
that even though we
can't see where they're
going to come out,
we can predict with
very high accuracy
where that hole is going
to be such that you even
slow old professors can
jump on these very fast mice
most of the time.
So, in fact, this burrow
is really nicely designed
by these mice to be very
effective for avoiding
predators.
And this makes even
more sense if I
tell you one of their major
competitors-- sorry, I should
have warned you, graphic photo.
One of their major
predators are snakes.
So you can imagine, just
like our tubing coming
in that entrance tunnel,
a snake coming in,
it's nice to have
a place to run out.
So clearly, these burrows are
complex, very interesting,
probably have a major fitness
component for these mice.
But the other reason
we're studying
this particular behavior is
because Wally Dawson, back
in the early '80s, did
a series of experiments.
He actually brought
these mice into the lab
and showed that they would
recapitulate their burrowing
behavior in a controlled
laboratory environment.
And even though the sample
sizes were very small,
he hinted that
they may, in fact,
have a strong genetic
component as well.
So the first thing
we wanted to do
was see if we could
recreate these experiments.
So here on campus, we
have our behavior room.
And what you're seeing
here are 10 large boxes.
In each of these boxes in
our controlled environment,
so we can control
temperature and lighting
and so forth-- each of these we
refer to as our Pheno-domes--
because in these
Pheno-domes we're
going to measure the behavior
of phenotype, their behavior.
We put a single
mouse into this box
that you can see is quite large.
It's filled with about a
ton and a half of dirt.
And we gave them this
nice slope because it
tends to elicit them to
produce a burrow in the center
of that slope as opposed to
hiding out in the corners.
So we leave them in these
boxes for about two days,
completely alone.
And then we come back after
two days, trap the mouse out,
and now we're going
to measure its burrow.
And we do this using what
we refer to as Pheno-foam.
So Pheno-foam is
the type of stuff
that if you have a hole in your
wall, you go to Home Depot,
you buy it, and
you squirt it in.
It fills the hole.
It expands, and then it hardens.
So what we can do is actually
make a cast of these burrows
and, thereby, have a physical
representation of the behavior
that that mouse was doing
over the last two days.
So next, I want to show you
a video of how we do this.
Just like the field,
we put our tubing down.
And out comes the mice.
You had no idea
that hole was there,
just like a predator
wouldn't know.
We trapped the mouse
out of the box.
And now, we're using
that same approach
to fill this in with Pheno-foam.
You'll see it come
squirting out that hole.
It indicates it's continuous.
We now let that harden
for a couple of hours.
And here's where having lots
of eager Harvard undergraduates
come in really helpfully in
the sense that they come in
and, literally, get their hands
dirty by digging out these
casts.
And I actually brought,
at the risk of being--
[LAUGHTER]
AUDIENCE: That
looks a lot better.
HOPI HOEKSTRA: So this is
one of the casts that's
produced by one of the mice.
You can see here is
that nest chamber.
And on this side, in fact,
there's nesting material.
And then these
are the blobs that
happen as that comes
out of the dirt.
But here's an actual sample,
one of our data points
from one of our
experiments, which
is one mouse over two nights.
So we, literally, have
mountains of data.
So what I want to
tell you about is
some very simple
measurements of burrows.
So today, I'm going to
talk about the length--
the total length of the tunnel,
the length of the entrance
tunnel which is just from the
entrance to the nest chamber.
And then I'm going to refer
to this as our escape tunnel,
and tell you about its
presence or absence.
There are lots of
things we can do
to measure this in
more complicated ways,
but today, we're going
to keep it really simple.
So the first thing when we
started this grand experiment
almost a decade ago was to get
mice, bring them into the lab,
and ask, will they still burrow?
This is now-- it's almost 30
years after Wally Dawson did
his first experiments.
So we can essentially
take mice--
Wally Dawson's
mice, in fact-- that
have been in captivity for
an additional 30 years,
meaning that they've
never seen dirt,
their parents have
never seen dirt,
and somewhere up
to 180 generations,
they haven't seen dirt,
and ask, will they
still produce a burrow?
So here's one of the
first mice we used.
We dropped it into
this big box of dirt.
And, immediately,
it started digging.
So it's clear, then,
that this behavior is not
strictly learned.
And even after being in
captivity, some of the strains
upwards of 180
generation, they still
build these
characteristic burrows.
Now, you could ask
about, is this learned?
Do they get better over time?
So we took some mice and
tested them multiple times.
And what we found was,
in fact, that they
do get a little bit better.
But they don't get a
lot better, at least,
not statistically better.
So here's some early data.
Here's this length
of the burrow.
Here's trial number 1, 2, and 3.
And you can see the first trial.
They don't build as long as
a burrow as the third trial.
And if we continued this
on, it would plateau off.
But this could be either that
they're learning or perfecting
their skills, or it could
be this is the first time.
They haven't been
in a mouse cage,
and they're sort of freaked out.
So to control for the
freak-out effect, what
I'm going to tell
you about is data
that comes from the best burrow.
And, usually, that's the
third trial of the three.
The second thing
we wanted to know
is, is there a difference
between males and females?
In fact, Wally Dawson, when
he did his experiments,
used only pregnant
females, thinking
they would be the
most motivated to dig.
So needless to say,
there were a lot
of bets going on in the lab.
Will the males build burrows?
And would they be better
than the female burrows?
Well, it turns out that
their burrows are identical.
So it doesn't matter if
you're male or female.
It doesn't seem to matter
if you're pregnant or not.
You build long burrows.
So I'm going to lump
the sexes together.
So next, what I want
to do is tell you
a little bit about
what we learned
from looking at
burrows in the field.
And then I'll move
on to tell you
about what we learned by
looking at controlled laboratory
situations.
So as I mentioned, you
can go out to this.
This is our beautiful burnt
peanut field in Alabama.
Here's our burrow.
We sent, again,
graduate students,
who came back very strong,
out into the field.
And here, for those
of you who may
be more molecularly oriented,
this is 15 mil conical.
It's about this big in size.
So you can see some of these
mice build very large burrows.
And, in fact, we had
to do two castings
of this particular burrow.
But what we were
interested in asking
is if we go throughout
the range of these mice,
do the burrows
all look the same?
And, in particular, in their
range in the Southeastern US,
they live in some
places, as I mentioned,
these beautiful sandy beaches.
And then our burnt
peanut field site
is, in fact, hard-packed clay.
So if they build
burrows in sand,
do they build burrows
that are bigger
because maybe that substrate
is easier to dig in?
Well, it turns out
the first observation
from digging up
multiple burrows at each
of these sites across
its range and sites
in particular that have
different soil concentrations
or compositions, that
burrow shape is conserved,
meaning in all of
these sites, they all
built burrows with this classic
entrance tunnel and escape
tunnel.
But there was an effect on
some aspects of burrowing.
That is, the depth correlated
negatively with silt.
In other words, if you are
in a high-clay environment,
the mice stop
trying to dig down,
and so the depth was less.
But, interestingly, the
length was the same.
So in other words, what
changed was not the length.
Length was statistically the
same in all of these habitats,
but the depths varied.
So in the sand,
there'd be burrows
that look like
this, which is more
flexible because in
the hard-packed clay,
the burrows had a
more shallow angle.
And this gave us some clue
that these mice actually
may be measuring the
length of the burrow.
But you may have already noticed
that the wild burrows I just
showed you a picture
of look, at least,
much longer than the burrow
path I showed you from the lab.
And, in fact, this was really
interesting because, in fact,
they are about twice
as long in the field
as they are in the lab.
And this could be a
number of reasons.
In the lab, we just
give them a fixed area.
We only give them two days.
Maybe this had an effect.
But there's one more
thing I haven't told you
about this particular species.
And that is, these guys, in
addition to being very cute,
are also one of the
few mammalian species
that's both genetically
and socially monogamous.
So when we jumped on these
mice as they come flying out
of this escape tunnel, it's
usually not a single mouse,
but often it's a male
and a female pair,
and sometimes with pups.
So the question
is, maybe they are
longer because males and females
are building burrows together
in the field, whereas in
our experiments in the lab,
we've always focused on a single
individual in the burrowing
box.
So the next question
we have was simply,
what happens if we put two mice
in one of our burrowing boxes
at one time?
So will they each dig their
own independent burrows
in this box?
Or will they cooperate?
And let me say I use this word
"cooperation" very loosely.
So you can decide
for yourself if you
think that this is cooperation.
So in this particular
pair-- this
is two siblings,
a male and female.
And when we came
back in the morning
after leaving them in this
box, actually for two days,
they both were in
a single burrow
that they, presumably,
built together.
So next, what we
wanted to know is,
are these burrows longer
when we put in pairs?
And we could do this
experiment in lots of ways.
We could put in male-male
pairs, female-female pairs,
opposite-sex pairs, et cetera.
And that's exactly what
we did and compared them
to the length of a burrow that
a mouse would build on its own.
And it turns out
that individuals
build burrows that are a
little bit over 40 centimeters.
When we put them
in same-sex pairs,
they build burrows
that are longer.
But if we put male and
female pairs together,
they, in fact, build
the longest burrows.
And this is particularly
interesting because what
this means is that these mice
are making different decisions
about how much effort to
put in their burrow-building
depending on who
their partner is.
So if you have an opposite-sex
partner, a potential mate,
maybe you want to put a
little bit more effort
into building that burrow.
So this is the outcome of now
putting these mice in a burrow
together, leaving
them for two days.
We don't see what they're doing.
We can only measure the outcome.
But next, I want
to tell you that we
have a way to spy on these mice.
I'm going to tell you more
about that in a minute.
But suffice it to
say, we can start
to watch what they're doing.
And what's really
interesting is that when
we put in male-female
pairs, it turns out
that they divide and conquer
in a different way in a sense
that they divide the labor
in an unequal way, in fact.
And we have to be careful
here not to anthropomorphize.
The males do most of the digging
of the actual tunnel, where
the female tends to follow that
male and clean up after him.
And she spends a lot of time
digging out and perfecting
that nest chamber.
But what's especially
interesting,
and please note sample
sizes here are very small,
but when we looked at, least
one, one same-sex pair,
this was not the case.
And, in fact, they
tended to contribute
in much more equal ways.
So this is research
that's ongoing.
This idea of how
decisions are made
based on who your partner
is in terms of cooperation
in this home-building exercise.
So now, I've told you
a lot about this one
particular species.
Next, what I want
to do is tell you
about other species in the
group because the first question
we have was, OK, this is a
really interesting and exciting
behavior, and maybe cooperation
has evolved in this case,
but what about the other
species in this group?
Do they all do the same thing?
Well, here's where we can
turn to some diversity
in this group.
And we can actually do
the same experiments
that I described for polionotus
and a bunch of other Peromyscus
species.
So the first thing
we were interested in
is the variation
among these species.
And here, I just want you to
focus on the major patterns.
Here, we're looking
at, in green,
is the frequency of burrowing,
how often they built a burrow.
And in gray, the
length of that burrow.
And there are a number
of things that you
should notice right away.
First, there's a lot of
variation among these species.
Some species, like polionotus,
did often and a lot.
But other species, like
eremicus, don't burrow at all.
And what's exciting
about this, actually,
is it turns out that
this really mirrors
what we know about their
natural history in the wild.
Eremicus is a rock mouse.
It doesn't dig in the wild.
It lives in rocky crevices.
So we think we're
capturing something
about their ecology--
their real ecology here.
The second thing
you'll probably notice
is that there's a lot of
variation among species.
And then the third
thing you'll notice
is that there seems to be
this really strong correlation
between how often you
dig and how long you dig.
But this just tells us
something about the length
of the burrows.
It doesn't tell us
anything about this shape
of the burrows.
So here are some cartoons.
These are not to
scale, but give you
a sense of the types of
burrows that are built.
So Peromyscus, in
fact, is the only one
that built this what I'll
call "complex burrow"
with an escape tunnel, whereas
these other ones either
dig these short little divots.
Let me reach in here.
So here's our
polionotus burrow here.
And this is the short,
little sock-sized burrow
built by some of these
other species here.
And there's one, this one
that builds long burrows,
but they don't have that
characteristic escape
tunnel associated with it.
And this data actually
becomes even more interesting
if we look at it in the
context of the relationships
among these species.
So you can think of
this as a family tree.
And what this tells us is that
even closely related species
can have wildly different
burrowing behaviors.
And the second thing it tells
us is that this escape tunnel is
unique and what
we call "derived."
That is, it looks like we're
looking at the, in terms
of evolution, the gain
of behavioral complexity.
In this makes things
for us more interesting
because there's lots of
ways to lose the behavior.
You could lose the
behavior of walking simply
by having a mutation in
your muscle, for example.
But, actually, the gain
of complexity to us
may be more interesting.
But what's particularly
nice about this data
is it highlights how,
for example, these two
sister species can have
very different burrowing
behavior even though they're
very closely related.
And what this
allows us to do now
is to take a genetic approach.
That is, even though these
are good species in the wild,
if we put them in the lab
and then caged together
a male and a female, and don't
give them any other choice,
these two can breed,
produce fertile offspring.
And we could start to
decode the genetics that
underlie the differences in
these two burrowing behaviors.
So for the rest of
the talk, I'm going
to focus on these
two species and try
to tell you about how
we're trying to identify
the genes that are responsible
for these differences.
So the first thing
we wanted to do
was to make sure that
we think that there's
a genetic component to these
differences in burrowing
behavior.
And to do that, we
did what's called
a cross-fostering experiment.
We take the maniculatus-- these
are the short burrowing mice--
and polionotus.
These are their little
jelly bean-sized pups.
And what we can do is take
the pups from maniculatus,
take them away from their
mom, give them a new mom,
either from the same
species or cross-foster them
with the long burrowing
species, and ask,
does it have an effect
who your mom is?
If your mom's a big
burrowing species,
do you somehow learn from
her to be a big burrowing
mouse as well?
So we could do
these experiments.
And suffice it to say, that
there is no measurable effect.
So, for example, for
maniculatus, a little burrowing
one, if you give the pups
a mom from that species,
they build short burrows.
But if you give them the mom
that builds long burrows,
they still build short burrows.
And, similarly, these
guys build long burrows
independent of their
mom as the same species
or a different species.
So this is a nice control to
say, OK, maybe your mom doesn't
teach you a lot about burrowing.
And that may mean that, in
fact, genes are important.
So here's where we get to
start to do the process.
So we can take, for
example, moms of polionotus,
cross them to dads
of maniculatus.
In fact, we did a reverse.
We take the dads of polionotus
and the moms of maniculatus,
crossed them together,
and make F1 hybrids.
Now, they have genes
from both parents.
And the first thing we want to
do is put them in a burrow box
and ask, what kind of
burrow do they make?
So, again, there's bets
going on in the lab.
Money was exchanged.
And maybe surprising to
us was that these hybrids
make perfectly
complex burrows that
are indistinguishable
from these parents.
That is, the length of the
burrows of the F1 hybrids
are similar to length
of the polionotus
and different from the
short maniculatus one.
And maybe even more stunning
is that polionotus always
builds an escape tunnel,
maniculatus never does,
and the F1 hybrids always do.
So consistent with
this depiction.
So now what we can do
is take these F1 hybrids
and make them back to these
small digging maniculatus.
We're increasing power,
taking the things that
are most different, and then
looking at what those mice do.
So let's just focus on
the length of the burrows.
So maniculatus
digs small burrows.
This is the length
of burrow here.
Polionotus digs long burrows.
Here is our F1 hybrids.
They build
polionotus-like burrows.
So big and long.
And then if you look at the
bottom, these backcrossed mice,
the next generation, when
we mated these with these,
first you'll notice there's
a continuous distribution.
Some are small.
Some are a little bit long.
What this means to me
as a geneticist is it's
not just a single gene.
Maybe not surprising that
this complex behavior
isn't controlled by one gene.
But the fact that we still get
mice in the second generation,
when we've diluted their DNA
with the short burrowing parent
once again, they still get
long burrowing mice-- suggests
that maybe the genetic
basis is quite simple.
So the next thing
we wanted to do
is not just look at the
length of the burrows,
but we wanted to know
about their size and shape.
And you have to forgive
me for my ability
to draw in PowerPoint,
but you get the idea.
So these are the
types of burrows
that we saw on these
backcrossed generation mice.
We got little burrows,
just like maniculatus.
We got big burrows,
just like polionotus.
But something interesting
happened-- that is, sometimes
we got long burrows
without an escape tunnel.
And other times, we got little
burrows with an escape tunnel.
So this, right
away, means that you
can separate the length,
genetically speaking,
the length of the
burrow to the presence
and absence of
the escape tunnel.
But even more interesting
is if we simply
count up in that second
generation hybrids
how many didn't build an
escape and how many did build
an escape, with real data,
it's never this close.
This is like dream data.
You can't get closer to 1 to 1.
And, again, what
this means to me
as a geneticist is that
the presence or absence
of that escape
tunnel, at least, is
consistent with a single
gene being involved.
And, boy, is it fun
to start thinking
about what kind of gene and
what kind of single gene
could be responsible for
the production of the escape
tunnel.
So now, we've got these clues.
And next thing, of
course, we wanted to know
is, where in the genome
are these genes that
are controlling these traits?
So don't get bogged
down in the details.
Suffice it to say, we
can put lots of markers
on lots of chromosomes.
And let's get their
statistical correlations
between the types
of burrows they make
and the types of markers
they have in the genome,
and what we found was
there are four regions that
are associated with
tunnel-building.
But even more
interesting, if we ask
what these four
regions in the genome
actually are associated
with, they're
associated with different
aspects of the burrowing.
So the three in
blue are associated
with the length of the burrow.
And the red one is associated
with the presence or absence
of the escape tunnel.
Now, this is perfectly
consistent with what I just
told you, and that was, we saw
that continuous distribution
which suggested a
handful of genes
may be involved in the
entrance tunnel length.
Here, we've noted three
regions of the genome.
And that the presence or
absence of the escape tunnel
is maybe controlled
by a single region,
like this one right here.
And even more interestingly
is that these two aspects
of burrow-building are
genetically separated.
They seem to be controlled
by different regions
of the genome.
In other words, this
tells us something
about how maybe a complex
behavior could be evolved.
And that is, in this case,
it could be simply putting
different behavioral
modules together.
For example, a module associated
with the length of the burrow
and then you add on to
the module associated
with the presence or absence
of the escape tunnel.
So now, we have these
regions of the genome.
And now, we want to
narrow in on genes.
So, again, don't get
caught up in the details,
but suffice it to say, we
focused on one of these peaks--
the one that was the biggest
and strongest and most
reliable and repeatable.
Here's our chromosome
now turned on the side.
We have markers.
We have this high association.
And what's neat is now we can
narrow down on the regions.
And in this particular region
of the Peromyscus genome,
there are only about
54 genes-- only.
So we're down from 20,000 to 54.
And this particular
region actually
has a high-density
olfactory genes.
So genes associated with
our ability to smell.
We thought, OK, those
are probably not
our best candidates
for burrow-building.
So let's exclude those for now.
So now, we're down
to about 30 genes.
And so, we can
narrow in on genes.
So we looked at their functions
and where they were expressed.
We got excited about
things, for example,
that were expressed
in the brain.
And we looked at
expression patterns.
That is, where are
these genes expressed?
And at what levels?
And importantly,
are they different
between the big burrowing mice
and the little burrowing mice?
And we found three genes
that showed a pattern
that we got excited about.
They were expressed
differentially.
That is, they produce
either different amounts
of protein or in
different places.
And in particular, one gene,
the gene in the middle,
showed a pattern that
we got really excited
about in the sense that
here's our polionotus,
the big building species,
big burrowing species.
This is the expression
of the gene.
It's high.
And it's statistically different
from the little burrowing
species, which is low.
But even more exciting
is the hybrids
have a pattern that's just
like the big burrowing species.
And why that's interesting
is because the hybrids,
just like the big burrowing
species, build a big burrow.
So here we have this
correlation, not causation,
between the two.
So to follow up
this experiment, we
had to bite the bullet in the
sense we could no longer avoid
looking at the mouse
behavior, but we actually
had to measure it.
So to do that, we've built what
we referred to as the mouse
equivalent of an ant farm.
So here's a two-dimensional
slice of a burrowing box.
And we could spy on the mice and
watch what they did at night.
So here's a mouse
back down to its nest
chamber, rolls around its back,
starts to dig out that nest
chamber, and then, ultimately,
will produce an escape tunnel.
So by watching them during their
nighttime activity period using
infrared cameras, we can measure
and quantify their differences.
And so we can do that
in an automated way.
For example, our mouse that
we can track using a computer
program, this mouse is dinking
around up here in the corner.
But here's the burrow that
it's building, shown in red.
The burrow that it's the
digging it's going to do
is shown in blue.
And we can actually quantify
the amount of digging.
We can look at one dig, how
much it digs, where it digs,
et cetera.
This got really
exciting until we
realized that for every mouse--
and remember we do three trials
and we're doing
hundreds of mice--
we had to watch eight
hours of videos.
And there are lots of
Harvard undergraduates,
as I mentioned before,
but this is a lot of work.
So what we did was
we actually came up
with a program
that measures this.
And I can already see, even
though this worked earlier,
that this video--
oh, it is working.
Here we go.
So here's a mouse digging.
This is sped up 900 times.
So you're watching eight
hours in just 30 seconds.
But you can see that this
particular polionotus,
the big digging mouse,
starts digging right away.
It builds its burrow.
And what we're
tracking here on top
is the amount of soil
that's getting dumped out
of the burrow, which is
correlated with what we're
tracking on the bottom which
is the invisible burrow that's
being produced.
So that's a typical polionotus.
And then we can
start to do this also
in our little digging
maniculatus mice.
And you'll be able to see
that these mice, just by eye,
have very different behaviors.
So this mouse runs around.
So the white is the cloud
space for the mouse.
It runs around
and, in fact, it's
built this little
ramp here because it
does these little jumps, these
little-- what are these called?
Backflips off the side.
It does this for several
hours till it gets stuck.
Keep going.
You can see it's not doing much.
Jumps around.
And then an hour or two
before the lights come on,
it quickly digs
this little burrow.
And then, that's it.
It sits in there for
the rest of the night.
And, in fact, we now
know that it anticipates
when the lights
comes on and digs
that burrow just
before it comes on.
So now, for each mouse,
we have images like this
or videos like this.
And we can start to quantify the
differences in the actual mouse
behavior that's responsible for
these differences in burrowing.
And here's some of the
things that we've noticed.
The first question we
could have is, maybe
they dig at different rates?
That polionotus just is faster.
Well, in fact, they are
a little bit faster.
They're about 1.2 times faster
than the little diggers.
But this only explains
about the 10% difference
in their overall final product.
But as you probably already
noticed from the videos
themselves is that
there's a big difference
in the amount of time
they spent digging.
In fact, these guys spend
significantly more time.
And this difference
in the amount of time
spent digging
explains almost all
of the difference in burrowing.
The other thing you probably
noticed from the videos
is the timing of
their burrowing.
Polionotus, we dropped
them in these ant farms
and they start digging right
away for the most part,
whereas maniculatus wait
till the lights come on.
So we considered these to
be our eager-beaver mice,
and these are our
procrastinators.
And why these patterns are
interesting is that all of them
suggest that
there's a difference
in overall motivation to dig.
And this really got us
thinking about maybe
the big difference
between these mice
is a motivational difference.
So the data that I just showed
you suggest that it's really
both the time they spent digging
and how eager they are to dig
is different between these
species-- with polionotus,
the big diggers, doing
it earlier and longer.
I also showed you
data early on that
there's this correlation
among species.
How often they dig is associated
with how long they dig.
All consistent with this idea
of differences in motivation.
And then the last
experiment we did
was look in now development
when they start digging.
How old are they when they first
start digging their burrow?
And it turns out maniculatus
digs its first burrow
about 25 days of age, whereas
polionotus starts digging
burrows as early 17 days of age.
And what this
suggests is they also
start digging earlier
in their lifetime.
And, in fact, these
mice that are precocious
are ones that dig
longer burrows.
So, again, this
all is consistent
with this overall difference
in motivation, which leads us
to what we call the
motivation hypothesis.
So now, if we go
back to thinking
about the types of genes
that may be involved
in these differences in the
burrows that are being built,
what we really would like
is a gene that maybe affects
motivation because that will
be consistent with this kind
of phenotypic data
we've been gathering.
So remember I told you we
have this great candidate
gene, this gene that
showed an expression
difference in the
right direction
that we thought, and the
F1s had the right pattern?
Well, I didn't tell
you what that gene was.
So let me end by telling
you about this gene.
This gene is called--
we call it Chrm5.
It's a muscarinic
acetylcholine receptor.
Don't worry about the details.
We know a little bit about
what it does in mice.
It's expressed in neurons
that have dopamine.
Dopamine is sort of
that reward feeling.
And it's expressed in regions
of the brain associated
with reward circuitry and
ones that are associated
with motor pattern and control.
So the first thing we
wanted to do is ask,
is it expressed in those
same regions in Peromyscus?
It is.
So the same areas
that are involved.
But maybe even
more interestingly,
we know from human studies,
genome-wide association
studies, that this
gene is associated
with nicotine addiction
and morphine addiction.
So our current hypothesis is
that these mice are actually
addicted to burrowing.
So here's where we are
right now with this project.
We're left with this question--
is this the right gene?
So it's going to
take us several years
now, I would suggest-- don't
tell any of my graduate student
I said that-- to
functionally validate this.
So what we'd like to do
is take the little digger,
transgenically
give it Chrm5 gene,
and see if we can get them
to produce a longer burrow.
So why, you may be asking--
OK, the mice are cute,
it's fun to watch
their burrows--
but why are you studying this?
And what is this going to
tell us more generally,
not even just about evolution
but about ourselves?
So let me end by saying that
the reason we chose burrowing,
in part, is because
it's a natural behavior.
So we've been using mouse
models for a long time
to try to identify
behavior genes that
may be important in behavioral
variations in humans.
And, certainly, that's
an area of research
that should continue.
There are lots of
great reasons to study
those types of behaviors.
But by studying a
natural behavior,
maybe this is a
complimentary way
to think about behaviors
that have naturally
evolved in human populations
as opposed to mutagenesis
screens in laboratory mice.
We also study
burrowing not again
because we're particularly
fond of dirt or burrows,
but because they're
easy to measure.
So we get around
this big bottleneck
in the field of how
to measure behavior.
And quite surprisingly,
in fact, it
turns out that this burrowing
behavior, even though it's
complex when we looked
about it, may, in fact,
be genetically simple.
But I'd like to argue,
then, that this behavior
in these particular
mice is potentially
going to be a great model for
understanding not only what
genes are involved but
how these genes influence
complex behaviors.
So I mentioned it's
really fun to think
about how changes
in just a few genes
affect this complex
burrow structure.
Here, I've given
you a hint at one
that may be involved in
motivation/addiction.
And maybe more interestingly,
that by studying
natural populations of
mice, we may, in fact,
be more likely to identify genes
or alleles that have withstood
the test of natural selection.
These are alleles in
mice that are viable.
They're doing well in
the natural environment.
And, hence, they may
be more likely to be
the types of alleles that may
be segregating or occurring
in other species,
including human.
So what our lab is trying to
do is take tools and techniques
from behavioral ecology,
neurobiology, and genetics
to try to make these links.
So let me end by thanking
the people that did the work.
So this project started
about 10 years ago,
literally in my garage,
with Jesse Weber here.
This is a photo from my garage.
Brant Peterson is the
postdoc that joined him.
Those ant farms
that I showed you,
we called them "Brant
farms," in honor of Brant.
And the project is
currently being taken over
by three fantastic
graduate students
here in the MCZ-- Hillery Metz,
Zain Ali, and Nicole Bedford.
And, of course, I need to
thank a lot of undergraduates
from Harvard,
Tufts, Northeastern,
wherever we can get them,
to help with our project.
And with that, I'm happy
to answer any questions.
[APPLAUSE]
JAMES HANKEN: Thank
you very much.
Well, those of you who need
to leave, please go out.
But Hopi's willing
to take questions
for the next few minutes,
if there are any.
HOPI HOEKSTRA: And I should
mention that afterwards,
if you want to
come see our casts,
and I brought a mouse
in dirt for folks
to see these incredible
diggers in real life.
Yes?
AUDIENCE: This idea of behavior
being genetically driven
is, highly-- I don't know
anything about this--
but it sounds very
fascinating and puzzling.
Addiction is something
where it's either on or off,
it seems like, if
you're addicted or not.
But how do you
explain behavior that
has to do with tunnels and
efforts in time or problems
when it's all about genes?
HOPI HOEKSTRA: So the
question is how can we
envision genes that control
how long you do something
as opposed to whether
it may be easier
to imagine how a change
in, let's say, one gene
turns a behavior on or off.
But how can you
imagine a gene that
controls how long
you do something?
That's a much more continuous
trait than an on/off trait.
And so, that's what's fun about
having this great candidate
gene in the sense
that we can start
to envision how this may work.
And so it could be that
these mice as they're
digging, the big diggers,
just simply get more reward
and are more than motivated
to keep going on and going on
to some level, whereas
the small burrower gets
a little reward but
just as at a little bit,
so it doesn't last very long.
That's maybe overly simplistic
way to think about it,
but really we can't
answer that question
about what's the mechanism
until we nail down this gene,
and then understand
how it works.
But that's exciting
part in some sense.
It's like, how do
these genes actually
produce the variation
in behavior?
And I don't think we have
a very good idea of that,
certainly not for a
representative number
of behaviors.
AUDIENCE: --that this
gene, candidate gene,
in the short diggers
are functional?
Or is it--
HOPI HOEKSTRA: So we know that
both-- oh, sorry, sorry, sorry.
Thank you.
Now, the question
is, what do we know
about this gene in the
small digging species?
Is it functional?
So as far as we can tell, if
you look at the sequences there,
it's there in the big species.
There are some differences
in the protein itself.
This is the receptor.
We know a lot about
its structure function.
So our first thing
was to say, OK,
let's recreate these proteins
and cell culture and ask,
do they signal at
different levels?
We did that.
We didn't see any difference.
But those kinds
of experiments are
often tough because you may not
be doing it in the right cell
type with the right
experimental conditions.
It could be that there's
a difference, but just
a small difference that is
biologically important that we
can measure.
But then when we did the
expression studies, that
suggested that maybe it's not
that structure of the protein,
it's just how much do you have.
So it could be that you could
have a difference because you
have a good protein or a good
signaler and a weak signaler.
Or it could be that they
signal the same way,
but you just have more of one.
So we're leaning towards
the latter at the moment.
AUDIENCE: What kind of
effects would epigenetics
have on behavior?
HOPI HOEKSTRA: So
epigenetics, what effect
does that have on behavior?
So we know an increasing
amount about epigenetics.
So I teach the Intro
course to freshman
on genetics and evolution, along
with three other instructors.
And I teach the
Epigenetics lecture.
Last year, when I
taught this lecture,
there was no
chapter in the book.
And this year, all of a
sudden, there's a chapter.
But it's still very small.
And the point is that
we know some things,
but we don't know of what.
We know that it's possible that
above the level of the genome,
which is what
"epigenetic" means,
you can modify genes, for
example, by methylating
them or putting tags on histones
where DNA is wrapped around.
That affect the accessibility
to those genes and, hence,
their expression.
And there are some very nice
studies in laboratory mice
and rats that suggest, for
example, their experience
as a pup can affect not
only their parenting style
when they're older, but
also that it can happen.
This is a little bit
controversial still.
But they show that there's
different methylation patterns
which changes the
expression that maybe I'm
responsible for that sort
of change through adulthood.
That's not controlled by any
changes in the DNA itself
but in the expression
of that DNA.
Because the studies that
we do here really focus
on the classic
Mendelian inheritance,
and we're doing crosses,
what we're focusing on
are the DNA base pair
changes themselves.
And because we've done this
cross-fostering experiments
that suggest that maybe learning
is, at least, not playing
a huge role in the system, we're
not as focused on epigenetics,
per se.
But there's a lot of
potential and a lot
of excitement about
that particular field.
AUDIENCE: So I may have misread
[? your information, ?] but
I thought that that gene
that you had identified
as a single gene,
that that one was
responsible for the presence of
the escape tunnel versus none.
So how does that tie in
with the motivation then?
HOPI HOEKSTRA: I wasn't
clear about this.
So this particular
region of the genome
that we went after because
it was the biggest, most
repeatable, and the
strongest genetic
or statistical signature
was one associated
with the length of
the entrance tunnel,
not the presence or absence
of the escape tunnel, which
in some ways is kind
of most exciting.
It turns out that it's
at the end of what
we think is a chromosome.
And that makes it a
little bit trickier
to narrow in on the
region because it's just
hanging out there at the end.
We're, definitely, it looks
like the next thing we're doing,
or we're actively doing.
We just haven't gotten
as far with that.
But that's going to
be a really fun one.
AUDIENCE: So how
did methylation get
to have that role in evolution?
And do you see methylation
in every species you look at?
HOPI HOEKSTRA: So methylation
associated with epigenetics?
Yup, yup, yup.
So methylation associated with
epigenetic changes, how does--
AUDIENCE: On/off?
HOPI HOEKSTRA: Yeah, the
on/off of expression of genes,
do we see that in all species?
And how could that have evolved?
So, again, this is
a little outside
of my area of expertise.
But suffice it to say, we
don't see it in all species.
We know it happens
in all mammals
that we've looked at so far.
But there are, certainly--
I don't think Drosophila,
for example, the other
the workhorse of genetics,
has any methylation.
So certainly in some
insects, it's not the case.
And how could this evolve?
I think there are people
that are certainly
interested in this topic.
But it often gets explained
as very Lamarckian.
So this idea that,
aren't you changing,
in some sense, your
genetic material
through the course of
[? a generation ?] that
can then be passed on but
without changing any DNA?
Doesn't that sound like
Lamarck's theory of the giraffe
stretches its neck,
it has a longer neck,
and then its offspring are
going to have longer necks?
And so it's often thought
of as anti-natural selection
or anti-Darwinian
evolution, when, in fact, I
think there are very plausible
explanations about how this
could evolve through--
that would make Darwin
very happy and very
consistent with his theory.
And that is, if this mechanism
that increases fitness
and there's some genetic control
of the stuff that then leads
to the methylation, then if
that increases fitness, then
that's going to be
promoted in the population.
And so as something
that I try to be
very clear with
my students about
is that there is,
at least, nothing
that I know of in terms
of epigenetics in the way
that machinery evolved
that's inconsistent
with Darwinian evolution.
JAMES HANKEN: Maybe
one more question.
AUDIENCE: I would like to ask
this question-- if you could
comment on the evolutionary
basis for these differences
in tunnel pattern.
I mean, what is the role
of predator, et cetera,
and whether or not a
person will be given
genes, [INAUDIBLE] if
he got into situations
where there are more predators?
HOPI HOEKSTRA: So what are
the ecological consequences
of having this burrow type?
And have we done anything
that suggests what's
driving this evolution of
this complex and certainly
energetically costly behavior?
So this is an area, again, of
active research in our lab.
We've actually have students,
in part funded by the MCZ,
to go out to the field to
do experiments in the field,
to ask are there differences
in, for example, survival
associated with the size
and shape of your burrows
within a population?
So for now, all I can say is
that we can make up stories,
these hand-wavy stories about
why this may be important.
But we haven't done the
elegant field experiments
that demonstrate that if you
produce a longer burrow that
actually translates
directly into increased
survivability to reproduction.
And that's something
that we really
want to do-- to fill out
the ecological five--
because, as I mentioned,
the goal of our lab
is to go from
ecology down to genes
and then back up to ecology
again because they're
missing the ecology of it.
JAMES HANKEN: So let me
first thank the audience
for coming out in force and
thank Hopi for a great talk.
[APPLAUSE]
And please see the mouse.
[LAUGHTER]
