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.