Hi, my name is Hopi Hoekstra and I'm a professor
at Harvard University. Today what I'm excited to do is to
tell you about the field of evolutionary genetics, and in particular,
the genetic basis of evolutionary change. I'm going to tell you two
stories, one about morphology and one about behavior.
So, here's the outline of the 3 segments of my presentation.
So what I'm going to do now is give you an introduction
and introduce you to some of the longstanding questions
in the genetics of adaptation, and give you a sense of how
we're addressing these questions. And then the second segment,
in particular, I'll tell you a story about how we're tracking down
the genes and developmental mechanisms involved in camouflaging
and color differences between two species of wild mice.
And then in the third segment, I'll tell you about how we're using
very similar approaches to track down genes involved in burrowing behavior
differences in these same mice.
So I want to start today by talking about Darwin. Because in
2009, we had a number of celebrations celebrating everything that
Darwin knew on his 200th birthday and on the 150th anniversary
of his magnum opus, On The Origin of Species. Now Darwin
certainly knew a lot about evolutionary change, but there is one thing
that he didn't get quite right. And that is the mechanism
of evolutionary change, or the genetic nuts and bolts about how
organisms adapt to their environment. Now Darwin knew the traits were
inherited, he knew that offspring resembled their parents, but he didn't
know how. And this maybe isn't surprising because during this
time, of course we didn't know about DNA or genes, much less
the whole genome. And that's really what I want to focus on
today, is this mechanism of how changes in genes actually produce
variation in phenotypes on which natural selection can act.
So I'm going to start by telling you a brief anecdote that links
Darwin to a second great discovery, and that is the discovery of
DNA. So what I'm showing you in this next slide is Darwin's
last publication. Now I don't expect you to read it, but i just want
you to appreciate the fact that you're looking at his last publication.
It was published in 1882, just two weeks before he died
in a prestigious journal called Nature. The title of this article
is called, "On the Dispersal of Freshwater Bivalves."
And what this really is, is a report of the finding of a freshwater
beetle clamped to its leg was a freshwater clam, or a cockle.
So why you may be wondering was this published in such a
prestigious journal even 100 years ago? Well, this actually
resolved this great debate about why freshwater cockles were so similar
among disjunct lakes in the British midlands. One hypothesis
was that these cockles could migrate from lake to lake,
thereby homogenizing the populations and thereby, making them
very similar in size and shape. But the big question always was,
well how do they get from lake to lake if they can't cross
terrestrial habitats? Well here was a mechanism. They could
hitchhike by attaching to things that could fly or traverse
this terrestrial habitat -- in this case by clamping to the leg of a
beetle. But that actually isn't the point of telling you this story.
The point of telling you this is to mention that Darwin was sent this
beetle with a cockle clamped to its leg by a shoemaker who
was working in the British midlands, who was an amateur naturalist.
And his name was Walter Drawbridge Crick. Now this name should ring a
bell, because his grandson was the one with his colleague, Jim Watson,
that made the second great discovery. That is the discovery of the 3-dimensional
structure of DNA. And it's in this DNA text that we find even more
evidence for Darwin's great theory, that is our 3 billion year
existence, the shared evolutionary history of all living organisms,
and the subject of what I want to talk about today. And that is the
mechanistic basis for evolutionary change.
So like Darwin, one of the big questions in evolutionary biology
today is what gives rise to this amazing diversity? How is variation
generated and maintained in natural populations?
But thanks to Watson and Crick, we can look for that answer
in the genetic code. So the big question that we're focusing
on is what is the genetic basis of fitness-related traits?
By fitness-related traits, I mean traits that improve the probability
of survival or reproduction of organisms in natural populations.
So finding the genetic changes or the precise DNA changes
that contribute to variations either between populations or between
species, is a fun endeavor. And we certainly can learn things about the mechanistic
aspects of evolutionary change. Like how do changes in genes
actually produce changes in phenotype? But I'd like to argue that
we can actually learn even more about the evolutionary process.
So what can finding genes tell us about how evolution works?
Well there are a number of longstanding questions that I think we're
just now starting to be able to answer, because we're armed
with molecular biology and the ability to link genotype and phenotype.
So I'm just going to list a few of these big questions.
So for example, how does evolution proceed? Is it through
many small changes? Many small mutations, each that have a small
effect on the trait, or can evolution take big leaps?
That is, can mutations have large effects that are beneficial?
We also want to know about the dominance of these mutations.
So, do adaptive alleles or mutations that appear, do they tend to be
dominant or recessive? So J.B.S. Haldane, one of the founders
of population genetics, argued that adaptive mutations tend to be
dominant. Because when they first appear, they're visible to selection
and then can quickly spread through the population.
Compared to a recessive mutation, which would have to build up enough
number in a population to be contained in the same individual,
and that recessive trait then expresses. We also want to know, how
many -- how do these mutations interact? So if multiple mutations
are responsible for changing the phenotype, do they interact
in a complex way? Or does each mutation additively affect
that trait? We also want to know where these mutations, these beneficial
mutations are. Do they occur in the protein itself? For example,
amino acid changes that affect that structure and function of that
protein. Or do they occur in what we call non-coding DNA,
which affects the regulation, let's say the timing or place of expression
of that protein. And then we want to know where these mutations come
from. So for example, if there's a change in the environment, do we have to
wait around for new mutations to appear in that population?
Or are there these mutations maybe at a low frequency in the
population already that are pre-existing that can be selected
on almost immediately? And then finally, if we find mutations in one
population that are responsible for an adaptive trait, and we
have a similar trait involved in another population, is it the same
mutations and same genes that are responsible for those
convergent traits? Now importantly, all of these questions that I've listed
don't have simple yes or no answers. And in fact, we're more
interested in the frequency, whether for example, more often
beneficial mutations occur in regulatory regions versus structural
regions. But even more importantly than that, we want to know
why. Why in some cases do we see protein changes and in other
cases we see regulatory changes. Now these I would argue are
still largely open questions, but questions we can start to answer
by making the connection between genotype and phenotype.
So the context in which we're studying the genetic basis of
adaptation looks like this. That is, we're trying to make the connection between
environment and phenotype. In other words, trying to implicate
a role for natural selection in driving that phenotypic variation.
That is, suggesting that the phenotypic differences affect fitness.
But we also want to understand the genes underlying that phenotypic
variation, and not just what those genes are, but how those genes
through let's say development, actually produce the differences
in variation. And then once we make those links, we'll have a much
more complete picture of the adaptive process. I think this is where things
can get really fun, because we can go back out in the wild and ask how traits
evolved in nature. So, to make these links between environment
and phenotype and genotype, my lab group is studying one particular
group of wild mice, commonly referred to as deer mice.
Or mice in the genus peromyscus. These are the most abundant
mammal in North America. And the reason we study them is because
first, they're found in almost every habitat type. So from the top of the Rocky
Mountains out to the shores of Maine, to the plains of Kansas, to the deserts
of Arizona. So they're very widespread in their distribution
and because they live in all sorts of different habitat types,
there's a lot of opportunity for local adaptation.
So in addition to all the variation that we find in the wild,
they also can be treated much like laboratory mice. That is
we can bring them into a controlled laboratory environments. They
breed in the lab just like laboratory mice, and we can do controlled
experiments. And finally, while we're still behind traditional
model organisms, my group, as well as others, is building a series of
genetic and genomic tools that are going to be useful in trying to
make these connections between genotype and phenotype. But I would argue
one of the main reasons for studying these mice is because
we have this amazing literature of natural history studies on their
ecology. That is, these mice have been studied for nearly a century
by natural historians who have described morphological, physiological,
and reproductive behavioral variation in natural populations.
Just to give you a sense of how these mice vary, here are just
a number of traits that I picked out of the literature that describe
traits that have been studied and traits vary either between
populations or between species of peromyscus species.
So they vary in body size, tail length, foot size, color patterning,
testis size, sperm morphology, et cetera. They vary in morphological
traits, physiological traits, and behavioral traits. So, using these
mice, we're trying to make those connections between genotype and
phenotype. And the next two segments of my presentation, I'm
going to focus on two of these traits. One morphological trait,
color patterning, and a second trait, burrowing behavior.
So, the second part of my presentation, what I'd like to do
is focus on the morphological trait. And in particular, camouflaging
and color differences between subspecies of peromyscus polionotus.
Both to understand the ultimate reasons why these color differences
evolved, as well as the mechanisms or the underlying genetics
contributing to these differences in camouflage and color.
And for the third part, we'll switch gears and focus now using
very similar approaches. But instead of studying a morphological
trait, we've substituted in a behavior where we're taking advantage of these dramatic
differences in burrowing behavior; there are species that build these
large burrows versus those that build small burrows. To try and
understand how genes can affect behavioral variations in natural
populations. So I've hoped to have gotten you excited about
biology, in the sense that we're at this amazing time where
we can use approaches like Darwin first did, that is studies of
natural history, observation and experiment in the wild,
but combine that with studies of modern day molecular
genetics. To try to understand the genetic basis of what Darwin
referred to as that perfection of structure and coadaptation which
most justly excites our admiration. So thank you very much
for your attention, and I hope you'll join me for the next two
segments, where I'll tell you about more detailed studies from
laboratory group, trying to connect genes and phenotypes for both
morphological and behavioral traits. Thank you.