SPEAKER: OK, it's a great delight to be here.
Welcome to Harvard.
I won't say I hope you come because I know you all will come.
And I'm excited to see many of you in life sciences want to be
all the budding scientists next year.
So what I'd like to do in the next 10 minutes
is tell you a little something about what Darwin didn't know.
Arguably, one of the most profound ideas in the sciences
is the idea of evolution by natural selection--
profound because it explains how the great diversity of organisms
that we see on our Earth first arose, but also profound
in its simple elegance.
Darwin's ideas, which he articulated in his 1859 book entitled
On the Origin of Species, was a great tome
that articulated these three pillars, different than the pillars
that Dr. Chetty just mentioned.
The idea is, first, if individuals within a population
compete, that is, there aren't enough resources
to support an infinite population size, therefore individuals will compete
to survive and reproduce; second, if there's variation in their ability
to compete, with some individuals being more competitive than others;
and third, if the traits that make those individuals more or less competitive
are heritable, then that population should evolve by natural selection.
Well, in his book, he spent decades providing evidence
for competition between individuals, both through observation
and careful experimentation.
He showed that in many populations there's
variation in individuals' ability to compete for resources
and survive and pass on their genes.
But the thing that was missing from his theory in 1859
was the idea of heritability.
Both Darwin and his colleagues surmised that many traits were heritable
based on the similarity of offspring to their parents,
but what Darwin didn't know, what was unknowable at the time,
because of course, this was before we knew about genes and genomes,
was exactly how traits were inherited.
So next, what I want to do is tell you a brief anecdote
that links Darwin to that second great discovery of how traits are inherited.
So here what you're looking at--
I don't expect you to read it, but just appreciate, maybe a few oohs and ahs.
This is Darwin's last-- thank you very much--
Darwin's last publication published just three weeks before he died in 1883.
And it's published in a preeminent journal called Nature, still a journal
that we publish in today.
It's entitled "On the Dispersal of Freshwater Bivalves."
And really, what this is is a little natural history
observation of a specimen of a beetle, and clamped to its leg
is a cockle or a freshwater clam.
Why was this published in Nature even a century and a half ago?
Well, it turns out this solved this great mystery
about how these clams could move from lake to lake in the British Midlands.
They could hitchhike on things like beetles that could fly them around.
But I digress.
The reason that I wanted to tell you about this story
is to tell you about how Darwin got his hands on this particular specimen.
It was sent to him by an amateur naturalist
who lived in northern England who was a shoemaker by training.
He sent the specimen to Darwin.
They had a flurry of correspondence.
Well, it turns out this young shoemaker's name was Walter Drawbridge
Crick.
And to those of you who are budding scientists, that should ring a bell.
Because nearly a century later, this shoemaker's
grandson, and his buddy, Jim Watson, a former Harvard professor--
with ideas either borrowed or stolen, depending on your perspective,
from Rosalind Franklin--
made this second great discovery, that is the three-dimensional structure
of DNA, which explained how that genetic information could be stored
and how it could be replicated and passed
on from generation to generation, what Jim Watson humbly
referred to as the secret of life.
And in this genetic code, we find even more evidence
for Darwin's great theory.
And now, as scientists were poised to ask questions
like Darwin did, how did this diversity of life first evolve, but now
we can look for answers in the genetic code.
So today I'm going to tell you a brief story about what
we can learn from identifying genes that contribute
to differences that matter in individuals' struggle
to survive and reproduce.
So the main actor in today's story is this little charismatic mini-fauna
shown here.
This is the deer mouse, which is the most abundant mammal
and widespread mammal in North America.
And if you were interested in going out and catching this mouse,
you would go to habitat that looks something like this, where
it's densely vegetated, dark soil.
And the mice you would catch would look something
like this, a typical mouse, a dark brown coat, a light-colored gray belly,
and a nicely striped tail.
But about 3,000 years ago, these mice colonized the beautiful white sand
beaches of the Gulf Coast of Florida and the Atlantic Coast of Florida,
where they inhabit these beautiful white sand dunes.
And if you go to these areas--
maybe it's spring break, for example--
and you catch a mouse, the same species of mouse would look very different.
It looks like this.
It lacks pigment on its face, on its flanks,
and on its tail, and only a tan stripe on its back.
Now, many of you, I'm sure, are thinking,
well, this makes sense, right?
They're camouflaged in their environment and probably can
hide from all those things that want to eat these poor little mice.
Well, that's a great hypothesis.
But as scientists, we want to test those hypotheses with experiments.
And that's exactly what a Harvard undergraduate who is working in my lab
did.
She set out around February, when it's awful and cold here,
to the beautiful beaches of Florida.
And there, she armed herself with hundreds of models of mice.
And those models of mice she either painted dark brown
or white with a tan stripe.
And she set them out at two field sites, one on the beaches,
one in the mainland.
She set them out randomly, in equal frequency,
and came back the next morning to see how many
were attacked by visually-hunting predators like owls, herons, hawks,
or foxes and coyotes.
And what she found, quite to our delight, was exactly what we thought.
That is, mice that match their habitat, like this one here or these two
top panels, had many fewer attacks than those that were mismatched.
So this experiment clearly demonstrated that color matters for survival
in these mice in their natural habitats.
But next, what we wanted to know is something about the genetic basis
of this difference.
So we moved from the field back into the lab.
And over the next several years, we interrogated the nearly 3 billion base
pairs in the mouse genome, which is comprised of about 20,000 genes,
to hone in onto one gene in particular, the melanocortin-1 receptor.
This particular gene, when we looked at it in dark mice versus light mice,
we found that there was one little change, a single DNA base pair
change that encoded an amino acid change in this receptor that
changed the function of that receptor, that
then changed the color of the mice.
So in other words, we were able to identify a genetic mutation, understand
how it affected the proteins, how it gave rise then through development
to this color variation, and ultimately, how
this affected the ability of the mice to survive in their natural habitats,
thereby illustrating the full picture of evolution by natural selection.
And we now use this model as a teaching tool
in Evolution and Life Sciences 1b, where we can actually
simulate mice running around on dark soil,
getting picked off by these hawks, or on light soil.
And then we can track how the different alleles, or different versions
of this melanocortin-1 receptor, change over evolutionary time.
But these beach mice still had a little more to tell us.
One day I was at a conference, sitting next to a colleague of mine who was
working at the University of Leipzig.
And he had just sequenced the entire genome from woolly mammoths.
He had three individuals where he could get DNA
from bones that were frozen in the Siberian permafrost.
And we're sitting next to each other, and I
said, let's look at the melanocortin-1 receptor.
He said, sure.
So he got onto his computer, pulled up the gene, and what he found,
quite to our surprise, was that the same gene, there
was the same mutation, which suggests that woolly mammoths may
have been polymorphic in color as well.
And it's not just mammoths.
It turns out that different mutations in the same gene
lead to differences in protein function, differences in color,
and differences in survival, like these white lizards that
live on the white sands in New Mexico compared to their dark ancestors.
For those of you who have a Labrador Retriever at home,
whether you have a golden lab or a black lab,
a single mutation in the melanocortin-1 receptor.
For those of you that have reddish hair and pale skin like me,
you may also carry a variant of the melanocortin-1 receptor.
And it's not just us.
It's our close ancestors or cousins as well.
About 6% of Neanderthals carry a variant of the melanocortin-1 receptor.
And hence, we think about 10% of Neanderthals also were red-headed.
So it's fun now to think about how tickled Darwin would be,
not only that his process of evolution by natural selection, that missing
piece has been discovered, but by studying the genes that give rise
to natural variation, we can learn things, not just about beach mice
and mammoths and lizards and how they survive,
but about ourselves, our pets, and our close cousins.
Thank you very much.