Session 9: Coevolution
Transcript of Part 1: Living Together: The Symbiosis of Host-Microbial Interactions
00:00:08.00 My name is Margaret McFall-Ngai 00:00:09.14 and I'm a professor 00:00:11.14 and the Director of the Pacific Biosciences Research Center, 00:00:13.14 School of Ocean and Earth Science and Technology, 00:00:16.07 the University of Hawaii at Manoa. 00:00:18.12 I'd like to start my lecture here 00:00:19.28 with thanking the iBiology team 00:00:21.22 for this opportunity to speak to you today 00:00:24.24 about the field of symbiosis. 00:00:27.12 So, the field of symbiosis is about living together 00:00:29.22 -- it's host-microbial interactions 00:00:32.15 that I will be talking about specifically today. 00:00:34.27 And there's a bit of a revolution in biology. 00:00:38.23 Symbiosis and host-microbial interactions 00:00:41.09 are taking center stage in biology. 00:00:46.11 And I'm going to talk to you today about why this is happening now 00:00:49.04 and exactly why we're sort of in the center of a revolution. 00:00:52.09 So, I'm going to start by talking about 00:00:54.20 the words that we use to describe symbiosis. 00:00:57.11 So, this person right here is 00:00:59.29 Heinrich Anton de Bary 00:01:02.16 and this particular person 00:01:04.25 lived in the 19th century, 00:01:07.04 and at the end of the 19th century 00:01:08.15 he coined the term symbiosis. 00:01:11.21 And the definition that he gave to this term 00:01:13.24 was the living together of unlike organisms. 00:01:16.23 And this particular definition of symbiosis 00:01:21.00 has remained with the field 00:01:22.19 until the present day 00:01:24.20 -- it's a very, very, very general way, 00:01:27.18 but very useful way 00:01:29.24 to think about this particular phenomenon in biology. 00:01:34.00 So, that said, 00:01:37.07 symbiosis is a bit of a catch-all term 00:01:39.05 with no information 00:01:40.19 concerning the effect of fitness. 00:01:42.22 So, what I'm showing up here is 00:01:45.06 I'm showing a very classic symbiosis 00:01:46.21 that a lot of people know of 00:01:49.28 and a lot of people think about, 00:01:51.18 and this is the symbiosis between 00:01:53.09 a clownfish and an anemone, 00:01:55.08 and they live together, persistently, 00:01:57.19 for much of their lives, 00:01:59.07 and it's a classic symbiosis 00:02:01.27 that you can think about. 00:02:03.00 But like I said, the word itself 00:02:05.05 confers no... no... 00:02:09.22 it's a catch-all word with no information 00:02:11.22 concerning the effect on the fitness 00:02:13.19 of either partner. 00:02:14.28 And so first I want to describe 00:02:17.18 what fitness means. 00:02:18.20 So, fitness is an individual's reproductive success, 00:02:23.10 and that is the number of offspring 00:02:25.10 that an individual leaves to the next generation. 00:02:28.06 And so let's think about this idea 00:02:32.14 in terms of symbiosis. 00:02:33.23 So, when we talk about fitness, 00:02:35.23 when we're talking about symbiosis, 00:02:37.14 I think there are... 00:02:39.02 I'm going to consider that there are two partners 00:02:41.03 -- there's symbiont #1 and symbiont #2 -- 00:02:42.17 and in a mutualism, 00:02:44.25 which is one of the types of symbiosis, 00:02:46.17 both partners will benefit, 00:02:49.12 and what that means is that both partners 00:02:51.07 will have more in the successive generations 00:02:57.02 from being a partner with the other. 00:02:58.11 And so in the case of the clownfish 00:03:00.17 and the anemone, 00:03:02.03 the clownfish gets a very safe place to live, 00:03:04.07 because the tentacles of the anemone 00:03:06.03 are harmful to other animals; 00:03:07.20 the fish, the clownfish, 00:03:10.28 has learned ways to avoid the danger 00:03:13.08 of living in the tentacles of this anemone; 00:03:15.23 and the anemone gains from having the fish there 00:03:20.25 because the fish releases ammonia 00:03:22.17 that is taken up by the anemone 00:03:24.16 and it's used in the energy production 00:03:28.01 of the anemone. 00:03:30.27 So, this is a true mutualism. 00:03:32.24 The next type of symbiosis I'm going to consider is commensalism. 00:03:36.13 In a commensalism, 00:03:38.14 one partner benefits and one partner is unharmed 00:03:41.19 -- there's no change in the fitness, 00:03:43.25 no change in the reproductive fitness. 00:03:46.29 So, what I'm showing here 00:03:48.25 is another example and this example, here, 00:03:51.05 is the shark/pilot fish example, 00:03:54.21 and in this particular case 00:03:58.15 what happens is is 00:04:01.25 the shark is a messy eater 00:04:03.21 and he eats fish and all sorts of various things 00:04:07.11 and food is released around him 00:04:10.20 and the pilot fish that are associating with the shark 00:04:14.24 take advantage of the fact that the shark is a messy eater. 00:04:18.22 In this case, the pilot fish 00:04:22.01 gained from living with the shark, 00:04:23.12 but it seems to have no effect on the shark. 00:04:26.02 And so in this case, it's very likely that 00:04:28.07 the pilot fish will leave more to the next generation 00:04:30.07 from living with the shark, 00:04:32.10 but the shark... 00:04:34.05 it won't affect the shark's fitness whatsoever. 00:04:36.05 The third example that I'm going to give 00:04:38.28 is the example of parasitism. 00:04:40.26 So, these are the three major types of symbiosis, 00:04:42.27 and in parasitism what happens is 00:04:46.15 one partner benefits and one partner is harmed. 00:04:48.22 So, I'm showing down here a tree, 00:04:51.10 and this particular tree trunk 00:04:53.28 has a large gall on it, 00:04:56.07 and the large gall is present 00:04:59.19 because there is a pathogen that is living, 00:05:05.00 a microbial pathogen is living inside this gall 00:05:06.04 and has created this large gall on this tree. 00:05:11.00 Now, the pathogen, that microorganism that's living in that gall, 00:05:14.06 benefits from living... 00:05:15.23 from parasitizing this tree. 00:05:17.29 The tree on the other hand 00:05:19.25 is harmed by this association, 00:05:21.10 so this is a classic parasitism. 00:05:23.24 So, one of the things I should mention is that 00:05:26.05 as the field has grown, 00:05:27.26 there's a little bit of misuse of these terms, 00:05:32.04 and this is one of the reasons 00:05:34.11 why I wanted to bring this up. 00:05:35.25 The term commensalism 00:05:38.22 is often used by the biomedical community, 00:05:40.13 in my mind and the mind of a lot of people who study symbiosis, 00:05:43.26 incorrectly. 00:05:45.07 And what they'll say is that 00:05:48.29 the microbes in your gut, 00:05:50.14 which I'm going to talk about a little bit... 00:05:51.24 the microbes in your gut are commensal, 00:05:54.11 and what this means is that 00:05:56.19 they have no effect on the host 00:05:58.24 -- they're benefiting but have no effect on the host. 00:06:01.14 But now we know that 00:06:03.29 they have a tremendous effect on the host 00:06:05.22 and are very often very important for our health, 00:06:10.01 and beneficial. 00:06:11.14 There are some in there that are likely commensal, 00:06:12.25 there are some in there that are likely 00:06:15.01 budding pathogens, 00:06:16.17 there are some in there that are likely, 00:06:18.00 or many in there, that are likely mutualists, 00:06:19.25 but we really can't categorize them, 00:06:22.14 so the very best thing to do in the instance 00:06:25.04 where you really don't understand 00:06:27.07 what type of symbiosis it is 00:06:29.19 is to just call it a symbiosis 00:06:31.19 and to call the partners a symbiont. 00:06:34.11 So, let's consider for a second 00:06:37.13 host-microbe symbioses. 00:06:38.29 So, what we're talking about is we're talking about 00:06:41.11 viruses, bacteria, protists 00:06:43.13 -- or single-celled eukaryotic cells -- 00:06:45.02 and fungi, living with animals and plants, basically. 00:06:48.18 So, the question is, 00:06:51.02 is this a rarity? 00:06:52.21 And I have to say that when I started my career 00:06:54.09 working in this field, 00:06:56.23 back in the early 1980s, 00:06:58.12 this was considered a very unusual feature of symbiosis... 00:07:02.20 symbiosis was considered an unusual feature 00:07:04.19 in the biological world. 00:07:06.16 And in fact, if you look at a textbook, 00:07:09.03 even today, 00:07:11.00 you will see that symbiosis is covered, 00:07:13.16 but it's covered in only a few pages 00:07:15.10 of a 1200-page textbook. 00:07:17.13 It was and is today still considered a rarity, 00:07:20.15 but I hope you convince you that 00:07:23.00 it's not a rarity at all. 00:07:24.26 But why was it considered a rarity? 00:07:26.26 Well, we would find it... 00:07:28.29 historically, we were looking at 00:07:31.01 unusual situations in things like 00:07:34.14 the hydrothermal vent symbioses in the deep sea. 00:07:38.10 Down at 2000 meters, you know, 00:07:39.21 you see these smokers down at 2000 meters, 00:07:42.01 and these particular smokers 00:07:44.11 would have associated with them 00:07:46.16 these very large tube worms, 00:07:49.00 and these large tube worms 00:07:51.01 had in association with them, 00:07:53.29 bacteria, and these bacteria 00:07:55.28 allowed these particular tube worms 00:07:57.27 to live on the chemical energy 00:08:00.12 that was provided. 00:08:02.02 So that was a true symbiosis 00:08:04.16 that's been studied by lots and lots of people. 00:08:10.01 Bioluminescence is another kind of symbiosis 00:08:14.13 and very many organisms who are bioluminescent, 00:08:17.16 not all, but many organisms that are bioluminescent, 00:08:20.05 are bioluminescent because they harbor 00:08:22.18 luminous bacteria in association with the organism. 00:08:27.04 So, in the case of this anglerfish, 00:08:28.12 up here in the angle 00:08:30.15 is a pure culture of a particular bacterial species, 00:08:33.26 and that allows the anglerfish 00:08:36.21 to use that light in its predation. 00:08:40.09 And then, lastly, 00:08:42.10 I'm going to give the example of coral reefs. 00:08:44.24 Coral reefs would not form 00:08:47.04 if they did not have a very... 00:08:49.17 a mutualistic symbiosis 00:08:51.04 with a unicellular organism called 00:08:53.29 zooxanthellae. 00:08:55.06 And these zooxanthellae live inside of the cells of corals 00:08:58.03 and they provide them with the photosynthate. 00:09:00.29 So, these zooxanthellae 00:09:06.03 are capable of photosynthesis 00:09:08.00 and they translocate the photosynthate to the host. 00:09:10.26 And so the zooxanthellae get a place to live 00:09:14.02 and the host coral is given the photosynthate, 00:09:18.27 and so they both benefit. 00:09:20.07 So, in all the cases I'm showing on this slide, 00:09:22.13 these are mutualistic symbioses, 00:09:24.26 and they're ones that have been 00:09:28.05 studied for over 100 years... 00:09:31.18 actually, not this one, 00:09:33.00 this one they discovered in the late 1970s, 00:09:34.10 but the many, many symbioses 00:09:36.07 that are mutualistic like this, 00:09:38.05 and kind of unusual, 00:09:39.21 have been studied for decades. 00:09:41.12 But now we're finding out that 00:09:43.13 nearly all animals and plants 00:09:45.20 are likely to have beneficial symbioses. 00:09:47.28 So, this is a whole new area, 00:09:51.27 this is a whole new finding, 00:09:53.17 and this new information 00:09:56.23 is from the last two decades of work. 00:09:58.29 And so I'm just showing 00:10:01.25 a whole array of animals 00:10:04.00 that are now known to have 00:10:05.27 beneficial symbioses with microbes. 00:10:10.29 So, I want to just take one minute 00:10:13.10 to pay tribute to what I... 00:10:15.22 the person who I consider 00:10:17.23 the mother of the field of symbiosis, 00:10:19.22 and this is Lynn Margulis. 00:10:21.07 And Lynn Margulis lived 1938-2011, 00:10:23.27 and she was the person 00:10:26.12 who felt that symbiosis was a major driver 00:10:28.17 in the evolution of animals and plants, 00:10:30.19 and she was always way ahead of her time. 00:10:33.20 She became famous f 00:10:35.19 or the endosymbiotic theory 00:10:38.11 of the origin of the eukaryotic cell, 00:10:39.17 and that is to say that bacteria 00:10:41.05 became symbiotic with other bacteria 00:10:43.03 and made a more complex cell. 00:10:45.14 And she showed that at the end of the 1970s, 00:10:50.06 it was very, very controversial, 00:10:52.00 she was way ahead of her time and always was, 00:10:54.09 but she is actually the person 00:10:57.07 who had the vision to say 00:11:00.19 exactly what we're seeing today, 00:11:02.04 and that is that symbiosis 00:11:04.02 is a major thing in biology 00:11:05.16 and has likely been over evolutionary history. 00:11:10.01 So, like I said, nearly all animals and plants 00:11:13.01 are likely to have beneficial symbiosis 00:11:16.05 and this is new information 00:11:18.12 from the last two decades of work. 00:11:20.12 And so what I'm showing here 00:11:22.27 is I'm showing a person, 00:11:24.09 and this person in this artistic rendering 00:11:27.18 is completely covered by microbes. 00:11:30.09 And we are, from the minute we're born, 00:11:34.00 through our life, 00:11:36.25 we associate very intimately with the microbial world. 00:11:39.06 And so we know now that you have as many, if not more, 00:11:42.25 microbial cells than human cells in your body. 00:11:45.04 So, you have about 10^13 human cells 00:11:47.08 and somewhere between 10^13 and 10^14 bacteria 00:11:50.00 that live with you, persistently, 00:11:52.26 your whole life and confer health. 00:11:57.06 So, the question is, 00:11:58.15 why didn't we know about this? 00:12:00.16 Why wasn't this more obvious? 00:12:03.07 Well, it turns out that there was 00:12:05.19 a huge technical problem 00:12:07.06 that we've been able to overcome. 00:12:09.05 And so, the technical problem 00:12:11.02 was a difficulty in identifying 00:12:14.15 and classifying the microorganisms, 00:12:15.17 and why we couldn't do that 00:12:17.15 was because most of these organisms 00:12:19.19 were unculturable under laboratory conditions, 00:12:22.19 and so they're called viable but nonculturable. 00:12:26.00 In other words, they live, 00:12:27.22 but we just can't bring them into the lab 00:12:29.28 and study them the way that we 00:12:33.13 would want to. 00:12:34.18 So, it's about less than 1% of the bacteria 00:12:38.15 that live in association with animals are culturable, 00:12:40.22 so this was a huge technical problem. 00:12:43.12 And so... because 00:12:45.17 we just couldn't know who they were. 00:12:47.10 The other thing was that... 00:12:50.15 another technical problem was that 00:12:53.12 they are relatively featureless. 00:12:55.12 So, what I'm showing here 00:12:57.17 is I'm showing a set of 00:13:00.12 different types of shapes and so on and so forth 00:13:02.27 that you might see 00:13:04.19 in different kinds of bacteria. 00:13:06.00 And so you might compare and contrast that 00:13:10.15 with the morphologies that you see of 00:13:13.09 very, very many plants and animals. 00:13:15.28 I mean, you can really, very well, 00:13:19.12 tell the differences between plants and animals; 00:13:21.21 with microbes, it's not so easy. 00:13:23.25 So, they weren't culturable 00:13:26.08 and you couldn't... they didn't... 00:13:27.26 they were pretty well featureless, 00:13:29.11 so these were big problems. 00:13:31.12 So, even though they're featureless, 00:13:33.06 we began to visualize microorganisms 00:13:36.03 back with Anton van Leeuwenhoek. 00:13:38.06 So, this is Anton van Leeuwenhoek 00:13:40.11 with, you know, several hundred years ago, 00:13:42.08 but he was a guy who 00:13:44.23 developed the very first microscopes, 00:13:47.06 and so he was the first person 00:13:49.26 who allowed us to visualize microorganisms. 00:13:51.16 And what Anton van Leeuwenhoek did was 00:13:54.15 he took a swab 00:13:56.19 and swabbed the inside of his cheek 00:13:58.10 and then he applied that to his microscope, 00:14:01.16 and he was able to see, for the first time, 00:14:05.00 microorganisms. 00:14:06.23 So, not only was he the first person to see microorganisms, 00:14:08.21 but he was the first person to see microorganisms 00:14:10.26 that associate with humans, 00:14:12.08 and those were the microorganisms 00:14:14.16 inside of his own mouth. 00:14:17.07 So, then we fast-forward 00:14:19.29 to the electron microscope, 00:14:21.27 and the electron microscope 00:14:23.21 was invented several hundred years later, 00:14:25.21 in the late 1960s, 00:14:27.28 and the invention of the electron microscope 00:14:31.02 allowed us to see much more detail in microorganisms. 00:14:34.17 And this was actually the microscope 00:14:37.10 that allowed Lynn Margolis, 00:14:39.22 who I spoke about earlier, 00:14:41.06 to visualize the complexity of the eukaryotic cell 00:14:44.04 and to resolve the fact that, 00:14:46.12 in fact, the eukaryotic cell 00:14:49.07 was the result of a symbiotic association 00:14:51.22 between microorganisms, 00:14:54.22 or among microorganisms. 00:14:57.02 So, then fast-forward a little bit more... 00:14:59.14 although... 00:15:01.22 so, these two characters, 00:15:04.26 Carl Woese and Norm Pace. 00:15:06.27 So, Carl and Norm were doing molecular biology 00:15:10.05 of microorganisms 00:15:11.20 at the University of Illinois... 00:15:13.22 well, Carl was at the University of Illinois 00:15:15.15 and he working with Norm Pace, 00:15:17.08 and they introduced the use of gene sequences 00:15:20.01 to determine relationships in the biological world. 00:15:22.08 So, notice that this is 1977, 00:15:25.04 so it's around the same sort of time that people 00:15:27.25 are beginning to think about using the microscope, 00:15:29.20 the electron microscope, 00:15:31.11 as a mechanism by which to classify the biological world, 00:15:34.26 but this was a new instrument 00:15:36.22 that Carl Woese and Norm Pace 00:15:38.24 introduced to the community of biologists. 00:15:42.08 So, the instrument was the 16S ribosomal RNA gene. 00:15:46.02 It's a highly conserved marker gene, 00:15:48.19 and the reason why this gene could be used 00:15:50.17 was because it's conserved throughout evolutionary history 00:15:53.12 and so it gives you an idea of 00:15:56.24 changes that are very, very old, 00:15:58.12 and would allow you to 00:16:00.21 classify all of the biosphere by molecular methods. 00:16:04.22 And this is the phylogenetic tree 00:16:07.26 that came as a result of the analysis 00:16:10.14 of the biological world. 00:16:12.07 And so what you'll see is you'll see that 00:16:16.15 there are the bacteria... 00:16:17.25 there are three domains of life 00:16:19.09 -- the bacteria, the archaea, and the eukaryea -- 00:16:21.26 and the eukaryea contain 00:16:25.12 the animals, plants, and fungi. 00:16:27.09 And so, look at... the animals, plants, and fungi 00:16:30.12 are just these three twigs 00:16:32.03 at the very top of the tree of eukaryea, 00:16:35.21 which is, you know, is showing us that 00:16:39.02 the vast diversity of the biological world 00:16:41.13 is invested in the archaea and the bacteria. 00:16:44.27 So this was a huge change in our world view. 00:16:49.03 So, how big was this change? 00:16:51.20 Well, let's go all the way back to Aristotle. 00:16:56.07 So, Aristotle was one of the first people 00:16:58.08 to classify the biological world, 00:16:59.28 and what Aristotle did was 00:17:01.25 he classified it based on what he could see. 00:17:04.01 So it's animals and plants, basically. 00:17:08.18 So then, you know, fast-forward, as I mentioned, 00:17:11.09 to Anton van Leeuwenhoek, 00:17:13.03 who saw animals, plants, and what he called animalcules. 00:17:16.15 And then, in the 1970s, 00:17:20.20 there was a worker named... 00:17:24.24 who used the electron microscope, 00:17:26.14 his name was Thomas Whittaker, 00:17:27.23 and he developed something called the five kingdom model, 00:17:30.07 and so the five kingdom model 00:17:32.15 had sort of the featureless bacteria and archaea, 00:17:34.22 down here at the base, 00:17:36.11 the protists above that, 00:17:38.07 and those are the eukaryotic cells, 00:17:40.07 and then up at the top he had 00:17:42.24 the fungi, animals, and plants. 00:17:47.20 So, Carl Woese and Pace, 00:17:50.07 looking at this in context with their sequencing, 00:17:54.10 what they had was these three domains. 00:17:57.23 And remember that all, all of this, 00:18:02.05 up here at the top, 00:18:03.24 all of this stuff up here at the top 00:18:05.13 is now invested in this group here. 00:18:09.23 So, it's a huge change 00:18:11.23 in the way we see the biological world. 00:18:13.17 So, what have we done? 00:18:15.12 We have moved from having visual analysis... 00:18:19.02 for a couple thousand years, 00:18:21.22 we looked at the biological world 00:18:23.20 and we classified it based on what we could see, 00:18:27.00 and now what Carl Woese and Norm Pace did 00:18:30.27 was they gave us molecular analysis. 00:18:34.26 And molecular analysis is the... are the genes, 00:18:37.15 and that allowed us to very correctly 00:18:40.12 organize the biological world 00:18:43.23 as it actually exists. 00:18:45.23 So, what we found, of course, 00:18:47.06 is that the biological world 00:18:50.09 is mainly microbial, 00:18:52.11 and the animals, plants, and fungi 00:18:54.02 are but a small patina 00:18:57.07 on the top of the microbial world. 00:18:59.21 So, what did this revolution mean for symbiosis? 00:19:04.21 So, what it meant was that we could identify microbes 00:19:10.09 and determine their relationships, 00:19:12.21 among them and between them, 00:19:14.06 even those that we not culturable. 00:19:15.15 We could extract the DNA from them and say, 00:19:18.04 what is the DNA telling us about who they are and what they are doing? 00:19:21.13 But at first, with Carl Woese in the very, very beginning, 00:19:25.14 sequencing was excruciatingly slow and expensive. 00:19:29.20 And then, around 2006, 00:19:32.10 something called next-generation sequencing 00:19:35.05 came onto the scene, 00:19:36.21 and this has been 00:19:38.22 the most important thing of the whole revolution. 00:19:42.21 And imagine... this was only 10 years ago. 00:19:45.19 So, what happened at this point 00:19:47.29 was that there was a technology-enabled transformation 00:19:51.24 in our ability to sequence quickly and cheaply. 00:19:55.01 So, what I'm showing in this graph 00:19:57.05 is I'm showing the cost of sequencing per megabase... 00:20:02.18 so, you see, in 2001, 00:20:04.14 it was up at about 6000 dollars a megabase, 00:20:07.23 and it followed Moore's Law 00:20:10.03 -- the doubling in computer power every two years -- 00:20:15.09 it followed Moore's Law for... 00:20:17.05 until about 2006, down here... 00:20:19.16 until about 2006, 00:20:21.25 and then next-gen sequencing was invented. 00:20:25.25 And look at what happened. 00:20:28.01 It went down from... 00:20:30.01 the cost went down from 600 dollars a megabase 00:20:32.06 to 35 cents in less than 10 years, 00:20:35.19 and now it's down to 3.5 cents. 00:20:38.13 And so this was incredibly enabling 00:20:41.05 to the community of biologists. 00:20:43.05 In other words, lots and lots and lots of people 00:20:45.23 had the resources 00:20:47.17 to be able to characterize the microbial world, 00:20:49.25 and so people have gone all around the world 00:20:53.18 characterizing the microbial world. 00:20:56.10 So, a whole frontier opens... 00:20:58.05 a whole frontier. 00:21:00.10 We can learn, who are the microbial partners 00:21:02.25 of animals and plants? 00:21:04.28 What are they doing? 00:21:06.11 How are they doing it? 00:21:07.18 And what is there importance to health and disease? 00:21:10.18 And so when you're thinking about a symbiosis 00:21:12.28 you think that many... 00:21:15.07 most of them are established new each generation. 00:21:17.19 Not all kinds are, 00:21:19.17 some of them the symbionts are passed 00:21:21.17 in or on the egg, 00:21:22.25 but most of them are established anew each generation, 00:21:25.14 just after birth. 00:21:27.02 And so when a baby is born, 00:21:28.27 what happens is at soon as 00:21:32.01 it goes through the mother's birth canal 00:21:34.12 it begins to acquire its microorganisms. 00:21:36.17 Then there's a development, 00:21:38.08 a trajectory that's not unlike 00:21:41.10 what goes on in the maturation of a forest 00:21:43.22 -- there's a succession of organisms -- 00:21:46.05 and in humans you get 00:21:49.09 a mature set of microorganisms 00:21:51.01 somewhere between the ages of two and four. 00:21:53.26 And then what happens is you become a stable association, 00:21:55.29 that changes some over life 00:21:59.22 with various changes and aging and so on, 00:22:02.22 but it's a fairly stable population. 00:22:06.19 So there's a trajectory 00:22:08.00 and we're learning a great deal 00:22:10.16 about how all of this works at this point, 00:22:14.04 but it's new data... 00:22:15.23 I mean, it's just the beginning of the field. 00:22:18.01 What have we learned so far? 00:22:19.28 What we have learned so far is that 00:22:23.01 for many, many, many animals, including humans, 00:22:25.26 the complexity is absolutely daunting. 00:22:28.22 And what do I mean by that? 00:22:30.17 So, let's take humans for example. 00:22:32.12 So, what I'm showing here is I'm showing 00:22:34.11 my favorite comedian, Woody Allen, 00:22:36.09 and I've been very generous with him 00:22:39.25 -- I'm making him 6 feet tall 00:22:42.05 or a little bit over -- 00:22:44.03 and so... but his, 00:22:46.14 if you compare the ratio is his size to a microbe's size, 00:22:48.26 2 meters to 2 microns, 00:22:50.22 so he's a lot bigger than a microorganism. 00:22:53.24 However, if you look at the number of genes 00:22:57.21 that Woody Allen has 00:23:00.19 compared to the number of genes that the microbes 00:23:02.18 associated with his body have, 00:23:04.05 the ratio is about 1:1. 00:23:07.18 If you look at cell number, 00:23:09.11 it's thought to be somewhere between 1:1 and 1:10. 00:23:13.11 In other words, there are about 10 times as many 00:23:15.29 microbes associated with you, 00:23:17.12 and that number has just this last year 00:23:20.11 become a little bit controversial, 00:23:21.24 so it's somewhere between here and here, 00:23:24.00 but that is to say that there are 00:23:26.25 just as many microbes associated with you 00:23:28.12 as you have human cells. 00:23:30.01 Then, if you look at gene diversity, 00:23:32.25 because instead of just... 00:23:34.09 so, you know, all of your eukaryotic... 00:23:36.14 all the human cells are of a single genome, 00:23:39.04 but the microbial cells are of 00:23:42.01 thousands, or hundreds if not thousands, of genomes. 00:23:46.07 The difference in gene diversity is thought... 00:23:48.22 for every single human gene 00:23:50.09 there are 200 genes of microbes, 00:23:53.11 so the gene diversity of microorganisms 00:23:55.09 is very much greater. 00:23:57.18 So at this point Woody Allen 00:23:59.22 feels pretty insignificant. 00:24:01.28 What I'm showing here is I'm showing the power of animal model systems 00:24:04.06 for the study of complex characters, 00:24:06.01 and the example that I'm using 00:24:08.07 is developmental biology. 00:24:09.23 And in development biology, 00:24:11.18 what I'm showing here is I'm showing 00:24:13.11 a fertilized egg, 00:24:15.22 and that fertilized egg goes from 1 cell to 10^13 cells 00:24:18.23 and produces something like 00:24:21.02 the miracle of George Clooney, my favorite actor. 00:24:23.14 So, this has been, this has been... 00:24:28.13 this approach has been extremely successful 00:24:30.18 to understand developmental biology. 00:24:34.10 So, what we've been able to do 00:24:36.29 is to take model systems, 00:24:38.15 you know, experiments that evolution has done, 00:24:40.14 and ask how, in this simple model system, 00:24:43.14 a particular developmental phenomenon 00:24:47.11 has been solved. 00:24:49.09 And so what I'm showing is 00:24:51.16 I'm showing an array of model systems 00:24:53.12 and I'm showing ones in which 00:24:55.27 Nobel Prizes have been awarded, 00:24:57.16 and it turns out that 6 Nobel Prizes 00:24:59.28 in developmental biology 00:25:01.14 have been awarded since 1995 and 2007, 00:25:04.06 and all 6 of them went to 00:25:07.24 individuals working on models. 00:25:09.09 So models have been an extremely valuable way 00:25:12.28 to study very complex characters. 00:25:15.09 So, because symbiosis 00:25:17.23 is such a complex character, 00:25:19.18 we feel, those of us in the field 00:25:22.03 who study models, 00:25:23.27 feel that it's a really good way to try to understand symbiotic associations. 00:25:28.10 So, we are developing, 00:25:30.02 the field is developing some models for symbiosis, 00:25:32.17 we're exploiting nature's toolkit 00:25:34.18 and, as I said, 00:25:36.22 evolution has done some enlightening experiments. 00:25:39.17 So what I'm showing here is I'm showing 00:25:41.27 a variety of them, 00:25:43.06 and so there are 00:25:45.05 various nematode symbioses 00:25:47.01 and various other invertebrate symbioses, 00:25:51.19 and we even have, over at UC Berkeley, 00:25:54.19 Nicole King studying the choanoflagellate symbioses, 00:25:58.13 at the base... 00:26:00.05 thought to be the base of the animal kingdom. 00:26:02.26 And then up here some vertebrate models. 00:26:06.05 Now, the vertebrates, 00:26:07.24 all the vertebrates have complex associations, 00:26:09.29 they have large consortia associated with them, 00:26:13.10 and so these people studying over here 00:26:15.10 are really interested in studying germ-free animals, 00:26:18.17 and so I sort of look at them as 00:26:20.21 engineered models. 00:26:22.10 Over here, many of them are studying 00:26:24.19 natural models 00:26:26.16 and these, the invertebrates are 00:26:28.21 naturally very simple associations, 00:26:33.01 and so they lend themselves to looking at a natural situation 00:26:35.12 and how that... 00:26:37.12 how the bacterium and the host animal get together 00:26:40.22 and maintain a stable association. 00:26:43.22 So, I... 00:26:46.17 my lab works on this beautiful animal, here, 00:26:48.24 the bob tail squid. 00:26:51.14 This is not a giant's hand, this is my technician's hand. 00:26:54.08 A very small squid that's indigenous 00:26:56.21 to the Hawaiian archipelago, 00:26:58.25 and this is the symbiosis that I've been working on 00:27:02.10 and that I would like to tell you about 00:27:04.10 in my next lecture. 00:27:07.02 Thank you very much.