Session 6: From Prokaryotes to Multicellular Organisms

Transcript of Part 3: The origin of animal multicellularity

00:00:07.27	So, animals are incredible!
00:00:10.06	Some of them can fly through the air,
00:00:12.09	some of them can swim.
00:00:14.06	Animals have incredibly diverse body plans,
00:00:16.29	for instance this nudibranch.
00:00:19.13	Some of them can pattern their coloration
00:00:22.02	in different ways,
00:00:23.19	like this moth,
00:00:25.09	and even what we might consider simple organisms,
00:00:27.20	like the jellyfish that we see here
00:00:30.06	or a sponge...
00:00:32.22	these are incredibly interesting organisms as well,
00:00:35.11	and all of these animals share in common
00:00:37.16	something important,
00:00:39.02	which is they are composed of thousands and millions of cells
00:00:41.16	and these cells are working together
00:00:43.19	to make the organism work properly.
00:00:46.11	How did this all come to be?
00:00:48.16	Well, that's the focus of the talk
00:00:50.21	that I'm going to give you today.
00:00:52.12	The work in my laboratory has to do
00:00:54.03	with the origin of multicellularity.
00:00:56.12	My name is Nicole King.
00:00:58.01	I'm an investigator with the Howard Hughes Medical Institute
00:01:00.04	and a professor at the University of California at Berkeley,
00:01:02.23	and I'm excited to be here today
00:01:04.15	to tell you about my research.
00:01:06.18	Now, in the closing line of
00:01:09.25	Darwin's Origin of Species,
00:01:11.17	he remarked on endless forms most beautiful,
00:01:13.19	and he was referring to
00:01:16.28	the incredible diversity of body plans that we can see here,
00:01:19.10	and much of his research and thinking
00:01:22.14	had to do with trying to understand,
00:01:24.22	how do we get this diversity of organisms?
00:01:27.00	And there's been a great deal of progress in this regard,
00:01:29.24	largely from the work of embryologists
00:01:33.07	and evolutionary biologists
00:01:34.22	and geneticists working together
00:01:36.13	to try to understand what are the molecular
00:01:38.20	and mechanistic underpinnings
00:01:40.12	of the diversification of animal body plans.
00:01:43.07	But, in fact, there's something else important
00:01:45.14	that we need to keep in mind,
00:01:46.26	and that is that animals are united
00:01:48.21	by their shared ancestry.
00:01:50.08	They all share a common ancestor
00:01:51.27	that you can see here, indicated by this red dot.
00:01:55.07	And, in fact, we know relatively little
00:01:57.03	about the nature of that organism.
00:01:59.10	We don't know much about what its biology was like
00:02:01.21	or what its genome contained,
00:02:05.00	and we know even less
00:02:06.25	about the organisms from which it evolved,
00:02:09.05	but we can make some reasonable inferences
00:02:12.17	about the prehistory,
00:02:14.07	the pre-metazoan history of animals.
00:02:16.15	What we can reasonably infer
00:02:19.01	is that there some important evolutionary processes
00:02:22.05	that predate animal origins,
00:02:24.16	and these have to do with the origin of multicellularity,
00:02:27.22	the transition from a single-celled lifestyle
00:02:30.09	to one with organisms that were capable
00:02:33.07	of being multicellular
00:02:35.15	and coordinating the activities
00:02:37.07	of their different cells.
00:02:38.28	So, what I'd like to talk to you about today,
00:02:40.23	in this first part of my talk,
00:02:42.29	is what are the big questions that we want to ask
00:02:45.23	when we want to think about reconstructing animal origins,
00:02:49.25	and I think there are some discrete questions
00:02:51.27	that we can start to address.
00:02:53.26	The first is:
00:02:55.24	how did genome evolution contribute to animal origins?
00:02:59.07	It's clearly the case
00:03:01.21	that different groups of organisms on the tree of life
00:03:04.21	have different types of genes in their genomes,
00:03:07.03	and what we're interested in in my lab
00:03:09.10	is trying to understand how changes in gene sequences
00:03:12.17	and the composition of genomes
00:03:15.10	might have contributed to animal origins.
00:03:17.06	In addition, we're interested in understanding
00:03:19.21	how genes that are required for animal development
00:03:22.09	might have functioned before animals first evolved.
00:03:26.13	One of the special things about animals
00:03:28.08	is they have different cell types
00:03:30.15	that are not found in other groups of organisms.
00:03:32.23	These might include neurons
00:03:34.20	or the epithelial cells that make up your skin
00:03:37.01	and the lining of your gut.
00:03:38.28	How did those specialized cell types first evolve?
00:03:42.25	And then, in a topic that
00:03:45.29	we didn't expect to be studying,
00:03:47.20	we find that we're becomingly increasingly interested
00:03:49.24	in how interactions with bacteria
00:03:51.21	might have influenced animal origins,
00:03:53.19	and I'm gonna come back to that topic in part two.
00:03:56.27	And, of course, in the background of all of this
00:04:01.01	we're interested in understanding
00:04:03.23	the evolutionary implications of multicellularity,
00:04:05.21	and this is a topic of research that is ongoing.
00:04:12.00	Now, historically,
00:04:14.12	we've been very interested...
00:04:16.15	evolutionary biologists
00:04:18.29	have approached the evolution of animals
00:04:21.00	and the diversification of body plans
00:04:23.01	by really focusing on the fossil record,
00:04:25.12	and fossils have been great.
00:04:26.26	They tell us about the age of certain animal groups
00:04:29.03	and they can tell us about the shapes
00:04:31.07	of some of their body parts.
00:04:33.24	So, for instance, these beautiful star-shaped objects
00:04:36.21	are actually spicules from an ancient sponge,
00:04:39.27	this is a hypothesized embryo
00:04:43.08	that has recently been recovered,
00:04:45.20	and here we have a fossil of a coral,
00:04:47.17	and so we can see the fossil remnants of animals,
00:04:50.24	but it really doesn't tell us the whole story.
00:04:52.20	It doesn't tell us how animals came to be
00:04:55.02	and it doesn't tell us how cells
00:04:57.23	in those ancient organisms actually interacted.
00:05:01.18	To really understand animal origins,
00:05:03.15	I think we need to be focusing
00:05:05.20	on comparing living organisms,
00:05:07.13	and so what I'm going to tell you in this first part
00:05:09.22	of my iBio seminar
00:05:11.17	is about an unusual group of organisms
00:05:13.15	called the choanoflagellates
00:05:14.29	and how they can give us special insight into animal origins.
00:05:18.21	And then I'm going to tell you about
00:05:20.23	how the study of choanoflagellates,
00:05:22.06	and comparisons with animals,
00:05:24.10	have started to reveal the genome composition
00:05:26.11	and biology of the first animals,
00:05:28.15	organisms that lived and died
00:05:31.04	almost a billion years ago,
00:05:32.27	and yet by studying living organisms
00:05:34.12	we can learn about how they functioned.
00:05:37.01	In Part II, which I will come to later,
00:05:39.08	I will tell you that some choanoflagellates
00:05:41.22	can transition between being single-celled
00:05:43.26	and multi-celled,
00:05:45.16	and I'll tell you about how that happens,
00:05:47.22	and in addition I will tell you
00:05:50.03	about how that's regulated.
00:05:51.26	There are intrinsic and extrinsic influences on this process.
00:05:54.21	But, let me get back to this big question:
00:05:57.21	how did animals first evolve?
00:06:00.01	And in particular, can we focus on multicellularity?
00:06:03.14	So, let me remind you that
00:06:06.05	animals are not the only multicellular organisms out there.
00:06:08.29	We are only one of many
00:06:11.23	diverse multicellular forms out there.
00:06:13.09	So, of course, we have representative animals,
00:06:15.21	but plants are a remarkable example of multicellularity.
00:06:18.28	There are also green algae,
00:06:20.28	the fungi,
00:06:22.11	and, on the far side of the slide,
00:06:24.12	the slime molds,
00:06:25.23	and there are, you know,
00:06:27.13	probably 20 different lineages that are multicellular,
00:06:30.01	and so each of these lineages
00:06:34.01	has an interesting history in terms of multicellularity
00:06:37.04	and you might think that we could compare
00:06:39.01	among all of these lineages
00:06:40.17	and learn something about the origins of multicellularity,
00:06:43.21	but it turns out that that's not possible,
00:06:46.00	and that's not possible for a few reasons.
00:06:48.05	One is that if we look at the cell biology
00:06:50.14	of each of these different multicellular lineages,
00:06:53.01	we see that their multicellularity
00:06:55.08	is set up differently.
00:06:56.24	So, some organisms like plants and green algae,
00:06:59.19	they have stiff cell walls
00:07:02.20	that mean that a cell is born where it's going to die,
00:07:06.18	they're not able to move around relative to each other,
00:07:08.29	whereas animals and the slime mold
00:07:12.12	don't have a cell wall and the cells are able to move around
00:07:15.09	and resculpt,
00:07:17.05	and that changes their ability to form complex structures
00:07:20.02	and interact with their environment.
00:07:22.17	So, these differences as the cell biological level
00:07:24.23	also help us to understand
00:07:27.03	something that we see at the level of genomes.
00:07:29.15	Now, you might imagine that you could
00:07:32.20	compare the genomes of different multicellular organisms,
00:07:34.26	and the genes they share in common,
00:07:36.22	which are indicated here at the intersection,
00:07:38.17	that these would be the ones involved in multicellularity,
00:07:40.20	but in fact that is not the case.
00:07:42.20	The genes found at the intersection
00:07:44.13	of comparing the genomes
00:07:46.09	of these different multicellular lineages
00:07:48.23	are the genes that are involved
00:07:51.18	in basic housekeeping functions in the cell:
00:07:53.26	DNA replication, translation, repair, etc.
00:07:58.09	The genes that are involved
00:07:59.05	in mediating interactions between cells
00:08:02.04	are actually the genes that are unique
00:08:04.18	within each of these genomes.
00:08:06.11	Why? Why is that the case?
00:08:08.22	Well, to explain why the genes for multicellularity
00:08:12.14	are different in each of these lineages,
00:08:14.07	I need to introduce you to a simple tree.
00:08:17.02	So, what I'm showing you here is
00:08:20.25	a very simple tree depicting the relationships
00:08:23.15	between three different major multicellular lineages
00:08:25.24	-- the animals,
00:08:27.11	which are also called the metazoa,
00:08:29.03	the fungi, which include the mushrooms,
00:08:31.23	and the plants --
00:08:34.04	and what I hope you can see is that
00:08:36.03	there are a few surprises in looking at this tree.
00:08:38.16	First of all, it's only recently been appreciated
00:08:40.27	that the closest living multicellular relatives of animals
00:08:44.23	are the fungi,
00:08:46.15	but the other thing I need to tell you
00:08:49.01	is that, by looking at diverse organisms,
00:08:51.28	it has now become clear that multicellularity
00:08:54.14	evolved independently in each of these lineages,
00:08:57.12	and that's depicted by these yellow bars.
00:08:59.22	So we think, actually,
00:09:01.15	that the last common ancestor,
00:09:03.13	for instance, of the animals and the fungi,
00:09:05.16	was not multicellular.
00:09:07.09	In fact, it was unicellular.
00:09:09.20	So, we have a rich history
00:09:11.19	of unicellular life
00:09:14.00	before the origin of these different multicellular lineages,
00:09:16.19	and then these lineages evolved multicellularity
00:09:19.08	independently.
00:09:21.06	Well, what are we going to do?
00:09:22.28	How do we operate within this framework
00:09:24.24	to learn anything about the nature
00:09:27.06	of the organisms from which animals first evolved?
00:09:30.05	Well, the way we do that
00:09:31.24	is to try to find lineages
00:09:34.00	between this long-extinct unicellular ancestor
00:09:38.06	and the origin of multicellularity, here,
00:09:40.11	in the animals.
00:09:42.04	And we do that using a group of organisms
00:09:44.12	that sits in this sweet spot on the phylogenetic tree,
00:09:47.10	and these are the choanoflagellates.
00:09:49.22	So, choanoflagellates were discovered long ago
00:09:53.03	and I'm going to tell you
00:09:54.09	quite a bit about them in the next few slides,
00:09:56.04	but I want to say that the evidence for them sitting
00:09:59.19	on this spot on the tree, as the sister group of animals, or metazoa,
00:10:03.13	is that they have shared cell biological features with animals
00:10:07.02	that are not seen anywhere else in diversity.
00:10:09.21	Phylogenetic analyses of diverse genes
00:10:12.12	have indicated that choanoflagellates
00:10:14.20	are the closest living relatives of animals,
00:10:16.18	and then I'm going to tell you, very excitingly,
00:10:18.21	that we've sequenced the genomes
00:10:20.25	of diverse choanoflagellates,
00:10:23.18	and when we compare the composition
00:10:26.04	of choanoflagellate genomes to those of animals
00:10:28.15	it's very clear that they share a very close relationship
00:10:32.24	to animals.
00:10:34.29	Let me tell you about these organisms
00:10:36.15	because you may never have heard about them before.
00:10:39.02	Choanoflagellates are single-celled microbial eukaryotes.
00:10:43.11	They're about the size of a yeast cell,
00:10:45.18	and they have some diagnostic features
00:10:49.04	that tell you that you're looking at a choanoflagellate.
00:10:51.24	They have a spherical or ovoid cell body.
00:10:54.10	At the top of the cell,
00:10:56.18	which we call the apical surface of the cell,
00:10:58.12	they have, as you can see in red here,
00:11:00.23	something that's called a collar,
00:11:02.25	and this is actually the source of the name choanoflagellate.
00:11:07.24	The phrase choano- refers to the collar,
00:11:09.29	and the choanoflagellates
00:11:12.19	also have a long flagellum,
00:11:14.06	and you can reasonably think of these cells
00:11:16.08	as resembling sperm cells,
00:11:18.16	with the addition of this collar.
00:11:20.23	Now, choanoflagellates are actually quite diverse.
00:11:23.18	They can come in many different shapes and forms.
00:11:26.19	So, almost all choanoflagellates
00:11:29.08	have a single-celled phase to their life history
00:11:31.23	as you can see here.
00:11:33.28	And, as I said, all choanoflagellates
00:11:36.10	have a flagellum and collar,
00:11:38.03	but some of them can form beautiful colonial structures,
00:11:41.06	such as you can see here.
00:11:42.26	This species can actually
00:11:45.02	fluctuate between colonial and single-celled,
00:11:47.25	and some of them form very ornate extracellular structures,
00:11:52.12	such as this beautiful organism,
00:11:54.24	which can actually biomineralized silica
00:11:57.00	to form a rigid structure that protects the cell
00:11:59.23	and mediates its interactions with other organisms
00:12:02.16	in the open ocean.
00:12:05.26	Why do choanoflagellates
00:12:08.07	have this combination of the flagellum and the collar?
00:12:11.16	What does that do for the choanoflagellate?
00:12:14.07	Well, let me show you.
00:12:16.00	What you're going to see, this is a movie,
00:12:18.04	and the flagellum is undulating back and forth,
00:12:21.15	and what this does is it actually creates fluid flow,
00:12:24.20	indicated by the arrows, that pulls water
00:12:28.14	along the surface of the collar,
00:12:30.22	and the flagellum pushes water out
00:12:33.25	behind the cell,
00:12:35.20	and so this has two consequences.
00:12:37.25	If the choanoflagellate cell is not attached to anything,
00:12:40.28	the movement of flagellum allows it
00:12:43.25	to swim along through the water column,
00:12:46.23	but that fluid flow also has a second important function,
00:12:49.17	and that is it allows the choanoflagellate
00:12:52.01	to pull bacteria up against the surface of the collar,
00:12:55.01	and so you can see in this picture right here
00:12:58.07	a bacterial cell that's been trapped
00:13:00.18	up against the side of the collar,
00:13:02.12	and so choanoflagellates actually have an important
00:13:04.25	and intimate interaction with choanoflagellates that...
00:13:08.16	errr, sorry, with bacteria...
00:13:10.14	that is essential for their viability.
00:13:13.03	Now, choanoflagellates were actually,
00:13:14.28	although they are not widely known,
00:13:17.04	choanoflagellates were actually first discovered
00:13:19.21	a long time ago, in the mid to late 1800s,
00:13:23.21	and people like Ernst Haeckel and William Saville-Kent
00:13:26.18	were obsessed with choanoflagellates.
00:13:28.29	Saville-Kent actually wrote a large monograph
00:13:32.24	called the Manual of Infusoria,
00:13:34.27	and there are many, many plates dedicated to the choanoflagellates,
00:13:38.23	showing their incredible diversity.
00:13:41.07	And, one of the things that excited Saville-Kent
00:13:44.00	about choanoflagellates
00:13:46.03	was that, to his eye,
00:13:48.15	they were completely indistinguishable
00:13:50.25	from another group of cells that he saw
00:13:53.01	in the natural world, and that was in sponges.
00:13:56.03	So, he noticed this similarity
00:13:58.07	between the morphology of choanoflagellates
00:14:00.09	and the morphology of sponges,
00:14:02.23	and from that he made the argument that
00:14:05.04	choanoflagellates and sponges might be closely related,
00:14:07.28	and you can see that similarity, I think,
00:14:10.09	even more clearly in this electron micrograph,
00:14:16.01	in which you can see, again, a choanoflagellate cell
00:14:18.22	with its cell body, its collar, and its flagellum,
00:14:22.06	and here you can see, in SEM,
00:14:25.15	a group of choanocytes,
00:14:27.25	that's the name for the collar cells in sponges,
00:14:30.21	arranged in a circle, and they're doing the same thing.
00:14:33.29	They're actually creating fluid flow to capture bacteria.
00:14:37.26	And, I think the power...
00:14:41.07	or the organization of these choanoflagellates,
00:14:44.00	or sorry choanocytes,
00:14:46.08	into this choanocyte chamber
00:14:48.14	is actually a very nice demonstration
00:14:50.22	of what happens when an organism becomes multicellular.
00:14:54.23	And so, an example of this,
00:14:56.18	I'm going to just show you in this movie,
00:14:59.01	is that the coordinated action of collar cells in sponges
00:15:03.14	allows for tremendous fluid flow.
00:15:06.19	And so, what you're going to see in this movie,
00:15:09.11	taken by PBS,
00:15:12.26	is that a diver comes in
00:15:15.13	and releases a cloud of fluorescent water
00:15:19.17	just near a sponge,
00:15:21.28	and now watch what the sponge can do with this,
00:15:24.04	just through the movement and activity of choanocytes.
00:15:28.06	So, the diver comes in,
00:15:30.12	this fluorescent dye is released near the sponge,
00:15:33.00	and now as the camera pan back you see that the sponge,
00:15:35.22	which we think of as a very simple organism,
00:15:38.17	is creating coordinated fluid flow
00:15:41.19	and sponges, through this action, are able to
00:15:44.10	capture enormous amounts of bacteria out of the water column.
00:15:50.25	So, choanoflagellates and sponges
00:15:53.20	are using an indistinguishable cell type
00:15:56.13	to capture bacteria out of the water column,
00:15:59.12	and it turns out that cells that resemble
00:16:02.12	choanocytes and choanoflagellates
00:16:04.12	are actually also found in other groups of organisms,
00:16:06.20	including in the form of epithelia and sperm.
00:16:10.04	When we map the distribution
00:16:12.14	of these types of cells, the collar cells,
00:16:14.20	onto a phylogenetic tree,
00:16:16.21	we can infer that because collar cells
00:16:19.27	are widespread within animals
00:16:22.01	and they're also found in all choanoflagellates,
00:16:24.17	then we can reasonably make an inference
00:16:26.24	that choanocytes and collar cells
00:16:29.03	were also present in their last common ancestor.
00:16:31.21	And we can also compare other features
00:16:33.21	of the biology of choanoflagellates and animals
00:16:36.11	within the context of a phylogenetic tree
00:16:38.21	and that brings us to a very exciting point,
00:16:41.00	which is that we can start to make
00:16:43.06	specific inferences about the cell biology
00:16:45.10	and life history of the first animals.
00:16:48.01	So, in this schematic,
00:16:49.21	what I'm showing you is what we now infer
00:16:53.01	to have been the case for the biology of the first animals.
00:16:56.18	We think that it had a simple epithelium,
00:17:00.08	this planar sheet of cells.
00:17:02.24	We think those cells were adhering tightly to each other.
00:17:06.21	We think that some of those cells, at least,
00:17:09.03	were capable of differentiating into collar cells
00:17:11.22	and, importantly, that those cells
00:17:14.02	were actually eating bacteria.
00:17:16.08	So, the first animals were bacterivorous.
00:17:19.13	We think that the first animal
00:17:22.00	also was capable of undergoing apoptosis,
00:17:24.01	or programmed cell death,
00:17:25.29	and that there were different cell types in the first animal,
00:17:28.18	indicative of cell differentiation within the soma.
00:17:33.01	Moreover, it's become clear,
00:17:35.13	by looking at the distribution
00:17:39.16	of different modes of sexual reproduction,
00:17:41.14	sperm and egg in animals,
00:17:44.02	it's become clear that the first animal
00:17:46.26	from which all living animals evolved
00:17:48.26	was capable of undergoing gametogenesis,
00:17:52.05	and that it produced differentiated eggs and sperm
00:17:55.21	and that these merged, in a process of fertilization,
00:17:58.24	to produce a zygote,
00:18:00.29	and then that zygote underwent multiple rounds of cell division
00:18:03.29	and cell differentiation
00:18:05.28	to produce this adult form that I just told you about.
00:18:08.11	So, I think this is an exciting time in which we're starting
00:18:11.19	to see the power of comparative biology,
00:18:13.27	and we can compare the cell biology of choanoflagellates
00:18:16.22	to animals
00:18:18.19	and start to really make specific inferences
00:18:20.16	about the biology of their last common ancestor.
00:18:24.02	Moreover, with the advent of genomic approaches,
00:18:28.02	we can start to learn something
00:18:30.11	about the genome of this organism.
00:18:34.00	Now, choanoflagellates
00:18:36.11	have really been relatively poorly studied
00:18:38.24	by molecular biologists.
00:18:40.18	There was this flurry in the mid-1800s
00:18:43.01	in which people were spending a lot of time
00:18:45.10	looking at and thinking about choanoflagellates
00:18:47.23	and then they were relatively forgotten
00:18:49.23	within the world of molecular biology,
00:18:52.22	and during the molecular biology revolution.
00:18:56.01	And so, one of the first things I did
00:18:58.13	when I started studying choanoflagellates
00:19:00.27	was to collaborate with the Joint Genome Institute
00:19:03.00	and the Broad Institute
00:19:04.17	to sequence the genomes of two different choanoflagellates,
00:19:06.27	Monosiga brevicollis,
00:19:08.23	which so far we have only seen in unicellular form,
00:19:11.14	and S. rosetta, which can be single-celled or colonial.
00:19:15.12	These genomes have a modest number of genes,
00:19:19.05	between 9-12000 genes in their genomes,
00:19:22.03	and we can compare the composition
00:19:24.08	of those genomes with animal genomes
00:19:26.14	to make inferences about the genome of their last common ancestor.
00:19:29.22	In addition, we've recently started sequencing
00:19:34.16	the transcribed and translated genes
00:19:38.23	in the genomes of twenty other
00:19:42.10	additional choanoflagellates that are in culture,
00:19:45.07	and I just want to make the point that
00:19:47.15	there's a lot of diversity in choanoflagellates,
00:19:49.19	and by surveying the genomes
00:19:52.05	of many, many different choanoflagellates
00:19:53.28	we're starting to get an increasingly complete
00:19:56.01	and complex picture
00:19:58.07	of what the genomic landscape of animal origins
00:20:00.18	might have been.
00:20:02.06	Now, I'm not going to tell you about
00:20:04.03	all of the different genes that are found in that ancestral genome,
00:20:06.14	but I do want to summarize some of the exciting findings.
00:20:10.03	When we analyzed these genomes,
00:20:13.03	we particularly focused on genes
00:20:16.06	whose functions are required for
00:20:19.26	animal multicellularity and animal development,
00:20:22.03	and in particular we focused on genes that are required
00:20:24.18	for cells to adhere to each other,
00:20:26.19	genes that are involved in cell signaling,
00:20:28.13	that is, allowing cells to talk to each other
00:20:30.08	and coordinate their functions,
00:20:32.16	genes that are required for gene regulation,
00:20:34.25	which allows one cell to differentiate
00:20:36.19	its function from the other,
00:20:38.25	and genes that are involved in interactions
00:20:41.07	with what's called the extracellular matrix, the ECM,
00:20:44.08	and these are the genes and proteins
00:20:46.16	whose functions allow cells to create this matrix,
00:20:50.27	this structure that provides a landing spot
00:20:54.27	and scaffold for cell-cell interactions.
00:20:57.21	So, we can think about these as being essential functions
00:21:00.00	for animal multicellularity.
00:21:02.17	Many of the genes that are required for these processes
00:21:04.17	in animals
00:21:06.19	had not previously been found in a non-animal before,
00:21:09.14	and now we can ask, if we look at choanoflagellates,
00:21:12.06	what does that tell us about the ancestry of these genes?
00:21:15.15	Are they really animal-specific?
00:21:17.10	Or, might some of these genes
00:21:19.06	have evolved earlier to serve other functions?
00:21:21.24	Now, remember,
00:21:23.04	we have to do this within a phylogenetic framework,
00:21:25.06	and so we're going to ask two different questions.
00:21:29.00	If we are focused on these classes of genes,
00:21:31.14	what fraction of them seem to be restricted to animals?
00:21:35.04	And, what fraction of them
00:21:37.05	are also in choanoflagellates
00:21:38.22	and therefore, we infer,
00:21:40.15	present in their last common ancestor with animals?
00:21:42.25	Some of these genes might have evolved
00:21:45.02	much earlier in the colonial and unicellular
00:21:48.02	progenitors of animals.
00:21:50.11	So, when we do these types of comparisons,
00:21:53.02	and when we did them, it was really quite exciting.
00:21:56.08	I think it helped to motivate
00:21:58.08	a lot of the future study for choanoflagellates,
00:22:00.15	and that's because choanoflagellates
00:22:03.17	turned out to express many different components of the...
00:22:07.29	or, many different genes that are required
00:22:11.12	for the functions that I was just discussing.
00:22:13.29	So, we can find genes that are required
00:22:16.12	for cell signaling in animals,
00:22:18.08	including things like...
00:22:19.27	it's a bit of a chicken soup,
00:22:21.22	but the GPCRs, these are protein coupled receptors,
00:22:24.02	the receptor tyrosine kinases,
00:22:26.09	proto-oncogenes like Src and Csk.
00:22:29.10	We can also find genes whose functions
00:22:32.07	are both necessary and sufficient for allowing cells
00:22:34.11	to stick together.
00:22:35.28	These include the cadherins and C-type lectins.
00:22:38.01	We can find representatives of various transcription factors
00:22:41.18	that are involved in gene regulation,
00:22:43.03	Myc, p53, and Forkhead,
00:22:45.12	and we even find genes that are involved
00:22:48.13	in forming and coordinating the interactions
00:22:52.24	of animals cells with an extracellular matrix.
00:22:55.13	But, remember,
00:22:57.00	we're finding representatives of these genes
00:22:58.21	in non-animals, the choanoflagellates,
00:23:00.27	and so I think an exciting future area of research
00:23:03.08	is to try to figure out
00:23:05.15	how these genes function in choanoflagellates,
00:23:07.25	and try to make inferences
00:23:10.13	about how they might have functioned
00:23:12.07	in our long-ancient progenitors.
00:23:14.17	Now, it was very exciting to find all these animal genes
00:23:17.06	in choanoflagellates,
00:23:18.29	but I think we all need to agree that choanoflagellates
00:23:21.03	are not animals.
00:23:22.21	So, what makes animals different?
00:23:24.20	And, what is exciting is that these genomic interactions...
00:23:28.22	or, sorry, these genomic comparisons,
00:23:30.24	allow us to learn about
00:23:33.27	what types of genes and genomic innovations
00:23:36.12	might have actually contributed to animal origins.
00:23:38.20	And so, when we look at the gene complement of animals
00:23:42.20	and compare it to choanoflagellates
00:23:44.20	we find that there are some genes
00:23:47.02	that thus far have never been found
00:23:49.13	in a non-animal.
00:23:51.06	And so, these are representatives
00:23:53.11	from each of these different
00:23:56.13	groups of processes as well,
00:23:58.17	and they include important genes involved
00:24:00.17	in developmental signaling,
00:24:02.27	one special class of cadherins,
00:24:05.07	the classical cadherins,
00:24:07.06	that are essential for allowing epithelial cells to interact,
00:24:10.19	important and famous developmental patterning genes
00:24:13.21	like the Hox genes,
00:24:15.17	so far have never been found in a non-animal,
00:24:17.19	and very specialized forms of extracellular matrix components,
00:24:21.00	including the Type IV collagens.
00:24:23.19	So, having genome sequences
00:24:26.22	from living organisms
00:24:28.25	has now allowed us to reconstruct,
00:24:30.28	in increasing detail,
00:24:32.06	the genomic landscape of animal origins.
00:24:36.03	So, what I want to say, then,
00:24:39.17	and what I've tried to say in Part I,
00:24:41.26	is that by studying
00:24:45.07	these previously enigmatic organisms,
00:24:47.27	that had been poorly studied,
00:24:50.16	we're starting to grow and develop
00:24:53.01	a new model for animal origins,
00:24:55.12	and we can study these organisms, now,
00:24:58.15	in a modern context to start to learn
00:25:01.07	about animal origins and details.
00:25:03.14	So, what I've told you in this first section
00:25:06.00	is that choanoflagellates, the study of choanoflagellates,
00:25:08.10	has illuminated the cell biology and genome
00:25:11.14	of the progenitors of animals,
00:25:13.19	and told us that those first animals
00:25:16.09	probably ate bacteria and they had collar cells.
00:25:19.02	And, the second important thing that we've learned
00:25:21.05	by studying choanoflagellates
00:25:23.18	is that a remarkable number of genes
00:25:25.10	required for multicellularity in animals
00:25:27.18	actually evolved before the origin of multicellularity,
00:25:31.19	and an exciting future area of research
00:25:33.25	will be to figure out what those genes were doing
00:25:36.23	before they were required for mediating cell-cell interactions.
00:25:41.23	So, that is the completion of Part I,
00:25:44.20	and in Part II
00:25:47.10	I will tell you about a transition to multicellularity
00:25:49.27	that didn't happen hundreds of millions of years ago,
00:25:52.25	but actually happens every day
00:25:55.25	in one particular choanoflagellate,
00:25:58.00	and I'm going to tell you about how that's regulated.
00:26:01.21	Finally, this work wouldn't have been possible
00:26:04.10	without the help of my past and current lab members,
00:26:07.27	and I'm also very grateful to all the collaborators
00:26:10.20	that made all this work possible.
00:26:13.10	Finally, I'm very grateful
00:26:16.07	for the generous support that's come
00:26:18.13	from the National Institutes of Health,
00:26:20.08	the Gordon and Betty Moore Foundation,
00:26:22.02	the Canadian Institute for Advanced Research,
00:26:24.07	and most recently the Howard Hughes Medical Institute.
00:26:26.10	Thank you very much.