The genetic basis of evolutionary change in morphology, phenotypic adaptations, and behavior

Transcript of Part 1: Introduction

00:00:00.18	Hi, my name is Hopi Hoekstra and I'm a professor
00:00:03.10	at Harvard University. Today what I'm excited to do is to
00:00:06.23	tell you about the field of evolutionary genetics, and in particular,
00:00:09.26	the genetic basis of evolutionary change. I'm going to tell you two
00:00:13.29	stories, one about morphology and one about behavior.
00:00:16.23	So, here's the outline of the 3 segments of my presentation.
00:00:21.12	So what I'm going to do now is give you an introduction
00:00:24.10	and introduce you to some of the longstanding questions
00:00:27.17	in the genetics of adaptation, and give you a sense of how
00:00:30.14	we're addressing these questions. And then the second segment,
00:00:33.21	in particular, I'll tell you a story about how we're tracking down
00:00:38.09	the genes and developmental mechanisms involved in camouflaging
00:00:42.11	and color differences between two species of wild mice.
00:00:45.08	And then in the third segment, I'll tell you about how we're using
00:00:47.25	very similar approaches to track down genes involved in burrowing behavior
00:00:51.25	differences in these same mice.
00:00:55.26	So I want to start today by talking about Darwin. Because in
00:01:00.06	2009, we had a number of celebrations celebrating everything that
00:01:05.07	Darwin knew on his 200th birthday and on the 150th anniversary
00:01:09.12	of his magnum opus, On The Origin of Species. Now Darwin
00:01:13.19	certainly knew a lot about evolutionary change, but there is one thing
00:01:19.00	that he didn't get quite right. And that is the mechanism
00:01:22.09	of evolutionary change, or the genetic nuts and bolts about how
00:01:26.02	organisms adapt to their environment. Now Darwin knew the traits were
00:01:29.04	inherited, he knew that offspring resembled their parents, but he didn't
00:01:32.14	know how. And this maybe isn't surprising because during this
00:01:36.02	time, of course we didn't know about DNA or genes, much less
00:01:39.08	the whole genome. And that's really what I want to focus on
00:01:43.21	today, is this mechanism of how changes in genes actually produce
00:01:47.26	variation in phenotypes on which natural selection can act.
00:01:52.08	So I'm going to start by telling you a brief anecdote that links
00:01:55.22	Darwin to a second great discovery, and that is the discovery of
00:01:59.06	DNA. So what I'm showing you in this next slide is Darwin's
00:02:04.24	last publication. Now I don't expect you to read it, but i just want
00:02:08.05	you to appreciate the fact that you're looking at his last publication.
00:02:12.08	It was published in 1882, just two weeks before he died
00:02:15.03	in a prestigious journal called Nature. The title of this article
00:02:18.23	is called, "On the Dispersal of Freshwater Bivalves."
00:02:21.28	And what this really is, is a report of the finding of a freshwater
00:02:26.10	beetle clamped to its leg was a freshwater clam, or a cockle.
00:02:30.15	So why you may be wondering was this published in such a
00:02:34.14	prestigious journal even 100 years ago? Well, this actually
00:02:40.06	resolved this great debate about why freshwater cockles were so similar
00:02:44.10	among disjunct lakes in the British midlands. One hypothesis
00:02:49.09	was that these cockles could migrate from lake to lake,
00:02:52.17	thereby homogenizing the populations and thereby, making them
00:02:56.23	very similar in size and shape. But the big question always was,
00:03:00.15	well how do they get from lake to lake if they can't cross
00:03:03.07	terrestrial habitats? Well here was a mechanism. They could
00:03:06.15	hitchhike by attaching to things that could fly or traverse
00:03:11.29	this terrestrial habitat -- in this case by clamping to the leg of a
00:03:15.22	beetle. But that actually isn't the point of telling you this story.
00:03:19.16	The point of telling you this is to mention that Darwin was sent this
00:03:24.08	beetle with a cockle clamped to its leg by a shoemaker who
00:03:28.22	was working in the British midlands, who was an amateur naturalist.
00:03:31.21	And his name was Walter Drawbridge Crick. Now this name should ring a
00:03:36.12	bell, because his grandson was the one with his colleague, Jim Watson,
00:03:41.04	that made the second great discovery. That is the discovery of the 3-dimensional
00:03:45.09	structure of DNA. And it's in this DNA text that we find even more
00:03:52.14	evidence for Darwin's great theory, that is our 3 billion year
00:03:56.20	existence, the shared evolutionary history of all living organisms,
00:04:00.18	and the subject of what I want to talk about today. And that is the
00:04:03.20	mechanistic basis for evolutionary change.
00:04:07.17	So like Darwin, one of the big questions in evolutionary biology
00:04:11.12	today is what gives rise to this amazing diversity? How is variation
00:04:16.02	generated and maintained in natural populations?
00:04:19.10	But thanks to Watson and Crick, we can look for that answer
00:04:22.11	in the genetic code. So the big question that we're focusing
00:04:26.02	on is what is the genetic basis of fitness-related traits?
00:04:30.14	By fitness-related traits, I mean traits that improve the probability
00:04:35.10	of survival or reproduction of organisms in natural populations.
00:04:39.07	So finding the genetic changes or the precise DNA changes
00:04:44.04	that contribute to variations either between populations or between
00:04:47.15	species, is a fun endeavor. And we certainly can learn things about the mechanistic
00:04:53.14	aspects of evolutionary change. Like how do changes in genes
00:04:57.15	actually produce changes in phenotype? But I'd like to argue that
00:05:00.21	we can actually learn even more about the evolutionary process.
00:05:04.11	So what can finding genes tell us about how evolution works?
00:05:09.03	Well there are a number of longstanding questions that I think we're
00:05:12.13	just now starting to be able to answer, because we're armed
00:05:16.06	with molecular biology and the ability to link genotype and phenotype.
00:05:20.17	So I'm just going to list a few of these big questions.
00:05:24.03	So for example, how does evolution proceed? Is it through
00:05:28.27	many small changes? Many small mutations, each that have a small
00:05:33.13	effect on the trait, or can evolution take big leaps?
00:05:37.08	That is, can mutations have large effects that are beneficial?
00:05:40.08	We also want to know about the dominance of these mutations.
00:05:45.07	So, do adaptive alleles or mutations that appear, do they tend to be
00:05:49.21	dominant or recessive? So J.B.S. Haldane, one of the founders
00:05:53.28	of population genetics, argued that adaptive mutations tend to be
00:05:57.19	dominant. Because when they first appear, they're visible to selection
00:06:01.03	and then can quickly spread through the population.
00:06:03.01	Compared to a recessive mutation, which would have to build up enough
00:06:07.14	number in a population to be contained in the same individual,
00:06:12.12	and that recessive trait then expresses. We also want to know, how
00:06:16.23	many -- how do these mutations interact? So if multiple mutations
00:06:19.26	are responsible for changing the phenotype, do they interact
00:06:24.03	in a complex way? Or does each mutation additively affect
00:06:28.07	that trait? We also want to know where these mutations, these beneficial
00:06:35.08	mutations are. Do they occur in the protein itself? For example,
00:06:39.17	amino acid changes that affect that structure and function of that
00:06:42.15	protein. Or do they occur in what we call non-coding DNA,
00:06:46.22	which affects the regulation, let's say the timing or place of expression
00:06:51.21	of that protein. And then we want to know where these mutations come
00:06:55.25	from. So for example, if there's a change in the environment, do we have to
00:07:00.13	wait around for new mutations to appear in that population?
00:07:03.08	Or are there these mutations maybe at a low frequency in the
00:07:07.18	population already that are pre-existing that can be selected
00:07:10.27	on almost immediately? And then finally, if we find mutations in one
00:07:16.03	population that are responsible for an adaptive trait, and we
00:07:19.01	have a similar trait involved in another population, is it the same
00:07:22.08	mutations and same genes that are responsible for those
00:07:25.16	convergent traits? Now importantly, all of these questions that I've listed
00:07:29.17	don't have simple yes or no answers. And in fact, we're more
00:07:33.08	interested in the frequency, whether for example, more often
00:07:37.13	beneficial mutations occur in regulatory regions versus structural
00:07:41.17	regions. But even more importantly than that, we want to know
00:07:44.26	why. Why in some cases do we see protein changes and in other
00:07:49.09	cases we see regulatory changes. Now these I would argue are
00:07:55.01	still largely open questions, but questions we can start to answer
00:07:58.25	by making the connection between genotype and phenotype.
00:08:01.20	So the context in which we're studying the genetic basis of
00:08:05.15	adaptation looks like this. That is, we're trying to make the connection between
00:08:09.16	environment and phenotype. In other words, trying to implicate
00:08:12.21	a role for natural selection in driving that phenotypic variation.
00:08:16.00	That is, suggesting that the phenotypic differences affect fitness.
00:08:20.02	But we also want to understand the genes underlying that phenotypic
00:08:23.29	variation, and not just what those genes are, but how those genes
00:08:27.12	through let's say development, actually produce the differences
00:08:30.28	in variation. And then once we make those links, we'll have a much
00:08:34.18	more complete picture of the adaptive process. I think this is where things
00:08:38.09	can get really fun, because we can go back out in the wild and ask how traits
00:08:41.21	evolved in nature. So, to make these links between environment
00:08:47.07	and phenotype and genotype, my lab group is studying one particular
00:08:51.26	group of wild mice, commonly referred to as deer mice.
00:08:55.05	Or mice in the genus peromyscus. These are the most abundant
00:08:59.10	mammal in North America. And the reason we study them is because
00:09:04.04	first, they're found in almost every habitat type. So from the top of the Rocky
00:09:09.03	Mountains out to the shores of Maine, to the plains of Kansas, to the deserts
00:09:15.21	of Arizona. So they're very widespread in their distribution
00:09:19.12	and because they live in all sorts of different habitat types,
00:09:22.06	there's a lot of opportunity for local adaptation.
00:09:24.23	So in addition to all the variation that we find in the wild,
00:09:28.14	they also can be treated much like laboratory mice. That is
00:09:32.14	we can bring them into a controlled laboratory environments. They
00:09:35.24	breed in the lab just like laboratory mice, and we can do controlled
00:09:39.22	experiments. And finally, while we're still behind traditional
00:09:45.05	model organisms, my group, as well as others, is building a series of
00:09:49.27	genetic and genomic tools that are going to be useful in trying to
00:09:54.17	make these connections between genotype and phenotype. But I would argue
00:09:58.00	one of the main reasons for studying these mice is because
00:10:01.11	we have this amazing literature of natural history studies on their
00:10:08.02	ecology. That is, these mice have been studied for nearly a century
00:10:11.13	by natural historians who have described morphological, physiological,
00:10:15.05	and reproductive behavioral variation in natural populations.
00:10:19.21	Just to give you a sense of how these mice vary, here are just
00:10:25.01	a number of traits that I picked out of the literature that describe
00:10:29.01	traits that have been studied and traits vary either between
00:10:32.14	populations or between species of peromyscus species.
00:10:36.12	So they vary in body size, tail length, foot size, color patterning,
00:10:39.27	testis size, sperm morphology, et cetera. They vary in morphological
00:10:43.05	traits, physiological traits, and behavioral traits. So, using these
00:10:48.20	mice, we're trying to make those connections between genotype and
00:10:52.01	phenotype. And the next two segments of my presentation, I'm
00:10:54.23	going to focus on two of these traits. One morphological trait,
00:10:58.04	color patterning, and a second trait, burrowing behavior.
00:11:01.18	So, the second part of my presentation, what I'd like to do
00:11:07.05	is focus on the morphological trait. And in particular, camouflaging
00:11:10.28	and color differences between subspecies of peromyscus polionotus.
00:11:16.02	Both to understand the ultimate reasons why these color differences
00:11:20.10	evolved, as well as the mechanisms or the underlying genetics
00:11:24.21	contributing to these differences in camouflage and color.
00:11:28.08	And for the third part, we'll switch gears and focus now using
00:11:32.24	very similar approaches. But instead of studying a morphological
00:11:34.26	trait, we've substituted in a behavior where we're taking advantage of these dramatic
00:11:39.18	differences in burrowing behavior; there are species that build these
00:11:42.24	large burrows versus those that build small burrows. To try and
00:11:47.11	understand how genes can affect behavioral variations in natural
00:11:50.21	populations. So I've hoped to have gotten you excited about
00:11:54.28	biology, in the sense that we're at this amazing time where
00:11:59.11	we can use approaches like Darwin first did, that is studies of
00:12:03.29	natural history, observation and experiment in the wild,
00:12:07.14	but combine that with studies of modern day molecular
00:12:10.15	genetics. To try to understand the genetic basis of what Darwin
00:12:14.26	referred to as that perfection of structure and coadaptation which
00:12:19.01	most justly excites our admiration. So thank you very much
00:12:23.00	for your attention, and I hope you'll join me for the next two
00:12:26.24	segments, where I'll tell you about more detailed studies from
00:12:29.19	laboratory group, trying to connect genes and phenotypes for both
00:12:33.11	morphological and behavioral traits. Thank you.