Virus Ecology and Evolution: from Virus Adaptation to Phage Therapy
Transcript of Part 1: Introduction to Virus Ecology and Evolution
00:00:14.17 Hi. 00:00:15.17 I'm Paul Turner. 00:00:16.17 And today I'd like to talk about the fundamentals of virus ecology and evolution. 00:00:20.10 This is not designed to be a comprehensive overview, but rather an introduction to the 00:00:24.20 very many ways that viruses interact with other organisms, and how they evolve on the 00:00:29.01 planet. 00:00:30.03 I'm currently the Chair and full professor of Ecology and Evolutionary Biology at Yale 00:00:35.20 University, and I also have an appointment in the Microbiology program at Yale School 00:00:40.20 of Medicine. 00:00:42.13 So, we can begin with a very fundamental question of, exactly what is a virus? 00:00:48.15 There are many ways of depicting the relationships between organisms on the planet as a way to 00:00:54.16 catalog biodiversity and evolutionary trees are generally the way that we use, within 00:01:00.07 evolutionary biology, a depiction of relatedness among biological species and groups. 00:01:04.21 So, for example, this is a depiction of the Tree of Life, but it's actually a pretty misleading 00:01:11.04 one. 00:01:12.04 Although many of the organisms are recognizable, here, they're really mostly drawn from only 00:01:16.00 one domain of life, the eukaryotes. 00:01:18.03 These are the most recognizable animals, plants, etc that most people are familiar with. 00:01:24.14 Instead, a more accurate depiction might be something like this wraparound tree, where 00:01:29.12 depicted in purple are the very many bacterial species, in this particular tree, that have 00:01:34.10 a name. 00:01:35.22 And another domain, shown in green, are the archaea which are, like the bacteria, single-celled 00:01:42.01 species, and they are more often found in extreme environments. 00:01:46.06 But you'll note in this tree that the archaea are close relatives to the groups with which 00:01:50.13 we belong, the eukaryotes. 00:01:52.23 So, for your reference, here are you on the tree. 00:01:57.00 And this Tree of Life also is a bit misleading in the sense that it cannot catalog the amazing 00:02:03.01 biodiversity of another very important group of biological entities on this planet, and 00:02:08.06 those are the viruses. 00:02:10.05 So, these three domains of life comprise only cellular life, and viruses are different because 00:02:16.07 they are not cellular. 00:02:18.00 At the top of this diagram, we see very familiar body plans of eukaryotes, including something 00:02:22.23 like a blue whale, a sequoia tree, and even single-celled eukaryotes are very common on 00:02:28.06 Earth. 00:02:29.10 The bacteria and the archaea, as stated earlier, these are single-celled organisms, so even 00:02:35.12 though many of them are close relatives -- closer than the bacteria than within the archaea 00:02:39.14 -- the body plans of bacteria and archaea are very simple in that they have only a single-celled 00:02:44.16 body plan. 00:02:45.16 Now, if we take a closer look at what the body plan is of a typical virus, it has a 00:02:50.18 protein shell as well as nucleic acid, either RNA or DNA, that's protected from environmental 00:02:56.05 degradation by this protein shell that has a very special name, called a capsid. 00:03:01.04 So, at the top we see, here, the influenza virus, which is a very typical virus that's 00:03:06.20 recognizable to most people by name, and it's shown that it's relatively a circular virus, 00:03:12.19 with the RNA as the nucleic acid and that's protected from the environment by a capsid, 00:03:18.04 whereas something like a phage, phage T4, this is a short form of the name bacteriophage, 00:03:23.14 which translates to eater-of-bacteria. 00:03:25.18 These are viruses that are specific to prokaryotes, and this phage, you notice, has a much more 00:03:31.23 elaborate body plan than an influenza virus. 00:03:36.05 But what they both have in common is nucleic acid that is protected from the environment 00:03:40.23 by a protein shell called a capsid. 00:03:43.08 A typical virus life cycle looks like this, in its most simple form. 00:03:48.03 As long as a virus attaches to some cell, that it has the proper protein binding recognition, 00:03:54.09 there's a possibility that it will get in, or that at least its nucleic acid will enter 00:03:59.07 the cell. 00:04:00.07 And, at this point, the primary mission of a virus is to hijack the metabolism of that 00:04:05.11 cell and divert those energy sources towards reproduction of viruses rather than normal 00:04:12.00 cellular function. 00:04:13.18 At this point, the particles can get to maturity within the cell and they can be released, 00:04:18.15 and go on and infect other cells. 00:04:21.10 So, this is very much a generalization, but it's a good way to think about the fundamentals 00:04:26.22 of how viruses replicate and reproduce. 00:04:29.19 So, now, you can really think of biological entities, perhaps life if you want to define 00:04:36.09 viruses as living, as being split into two basic body forms: the capsid-encoding organisms... 00:04:44.00 you can think of these as all viruses because they share the properties of nucleic acid 00:04:49.08 surrounded by a capsid, and the viruses themselves would be specific to either the archaea, the 00:04:54.24 bacteria or the eukaryotes; and ribosome-encoding organisms, the cellular ones, are quite different. 00:05:01.18 They are related to each other and they are the three major domains of bacteria, archaea, 00:05:07.09 and eukaryota. 00:05:08.20 So, the major mystery in all this is whether they all trace back to the same route. 00:05:15.08 This is really an open question in virology. 00:05:18.04 It deals with the evolution of virus origins and it's really unclear how viruses first 00:05:23.01 occurred on this planet, when did they first evolve, and, especially, whether they evolved 00:05:27.14 on the planet preceding cellular life. 00:05:30.24 One major idea that is popular, but is by no means the only idea of how viruses first 00:05:35.18 arose on the planet, is that they might have actually predated the evolution of all cellular 00:05:40.11 life. 00:05:41.19 And there's a key bit of data that supports this idea, in that, if you look at virus genes 00:05:48.03 and compare them in their genetic sequence to cellular life, that is available in genetic 00:05:53.10 databases, you often find a mismatch. 00:05:56.01 So, that suggests that viruses are not simply some more fundamentally simple version of 00:06:03.05 cellular life; instead, they might be something really fundamentally different that might 00:06:07.19 have predated cellular life altogether. 00:06:09.22 So, LUCA, here in this diagram, stands for last unique common ancestor, which is the 00:06:15.01 shorthand version of everything that cellular life perhaps traced back to. 00:06:19.22 And this diagram is indicating that there might have been an ancient virosphere, for 00:06:24.00 which all the viruses that are infecting the archaea, the bacteria, and the eukaryotes 00:06:30.14 existed alongside in this time period or even predating LUCA, and that, today, we see this 00:06:35.21 amazing biodiversity of virus types, but they might have been here billions of years ago 00:06:41.11 and even before cellular life. 00:06:44.02 So, the rest of the talk will feature several lines of evidence that suggest that viruses 00:06:51.08 just might be the most successful of Earth's inhabitants. 00:06:55.09 So, I'll go through five lines of evidence that really support what I would assert as 00:07:02.07 the extreme biological success of viruses relative to other entities on the planet. 00:07:07.12 The first will be growth potential; next, we'll talk about abundance, biodiversity; 00:07:12.13 adaptability; and, perhaps most important, it's very evident that viruses have huge impact 00:07:18.20 on other organisms on this planet. 00:07:22.09 First of all, growth potential... because there are so many different ways of cataloging 00:07:26.13 and determining what biological... biological success even means, let's begin with just 00:07:31.10 the sheer ability to grow, to reproduce, and produce copies of oneself. 00:07:37.01 So, growth potential can be pretty amazingly impressive for a lot of organisms. 00:07:44.09 Some eukaryotes, our close relatives, are able to reproduce very quickly, such as the 00:07:49.00 fruit fly has a very short developmental cycle, such that progeny are produced in a very short 00:07:54.13 period of time. 00:07:55.13 But, really, the abundance of the number of organisms that are... that can be produced 00:08:02.06 through reproduction... amphibians, they are also pretty impressive. 00:08:06.12 They can sometimes lay hundreds or thousands of eggs that will successfully develop eventually 00:08:11.12 into adults. 00:08:12.12 Now, the bacteria and the archaea, I would say, are even more impressive. 00:08:16.00 They undergo a form of reproduction called binary fission where each cell separates into 00:08:21.07 two daughter cells. 00:08:22.11 So, in this way they can grow very, very quickly, as long as there are abundant resources available. 00:08:27.11 So, I would say the bacteria and the archaea, on average, grow much faster than most eukaryotes 00:08:33.14 that we would consider. 00:08:36.14 All eukaryotes, bacteria, and archaea have genetic inheritance across generations that's 00:08:42.08 through DNA as the nucleic acid. 00:08:44.18 So, they sometimes do have this amazing growth potential, but let's keep in mind that the 00:08:49.09 only way that traits pass across generations is through double-stranded DNA inheritance. 00:08:56.06 Considering the viruses, they grow much, much faster than most bacteria, archaea, and eukaryotes. 00:09:02.18 So, the ability for viruses to enter a cell, hijack the metabolism, and make progeny can 00:09:09.06 sometimes lead to hundreds or thousands of particles exiting that cell. 00:09:14.08 So, this would be the case for bacteriophages that are infecting the bacteria and the archaea, 00:09:20.11 as well as viruses of eukaryotes. 00:09:22.17 If they infect a tissue, for example, in the human body, there can be an amazing capacity 00:09:27.04 for each one of those infected cells to produce upwards of 10,000 or more virus particles 00:09:33.13 per cell. 00:09:35.02 Also, in relation to inheritance across generations, I would say that the viruses have obviously 00:09:41.16 more options for how this occurs in the natural world, whereas the bacteria, archaea, and 00:09:48.00 eukaryotes are confined to largely DNA inheritance through double-stranded nucleic acid, both 00:09:53.23 double-stranded DNA and double-stranded RNA are possibilities for the nucleic acid inheritance 00:09:59.03 in viruses, as well as single-stranded forms of those nucleic acids. 00:10:03.17 So, essentially, viruses are covering the entire gamut of what is possible on this planet 00:10:08.17 for modes of inheritance through genetic... through genetic means. 00:10:12.15 So, now let's move on to talking about virus abundance. 00:10:16.11 And this is very amazing and, when you look at the numbers, you'll see that viruses easily 00:10:22.04 outnumber all other biological forms on this planet. 00:10:25.23 We'll begin with saying that viruses are very abundant and we know this because if you look 00:10:31.14 in natural habitats on Earth, sometimes these support cellular life and there's actually 00:10:36.23 an amazing capacity for cellular life to thrive in deep-sea vents and complete darkness, where 00:10:43.03 there are other forms of resources than the sun to produce progeny, ultimately, when you 00:10:48.20 look at very dry and hot regions, cold regions, atmosphere, soil... everywhere you find on 00:10:55.24 this planet the possibility of cellular life existing, you see alongside it viruses. 00:11:02.15 And the key thing here is that viruses generally outnumber cellular entities ten to one in 00:11:08.09 each of these environments. 00:11:10.09 Therefore, you can make some rough calculations and estimate, across this world, at any one 00:11:16.12 period of time, an estimate of some 10^31 particles of viruses in any instant is a very 00:11:23.02 reasonable one for the viruses on this planet. 00:11:26.23 And we all realize, hopefully you can remember, that nucleic acid exists in a compacted form 00:11:33.14 within cells and also within capsids of viruses, but if you just take these virus genes and 00:11:39.22 genomes, and you unravel them so that they're at their full length, and you lay them end 00:11:44.12 to end, off of the Earth's surface, this would extend to 250 million light years away, which 00:11:49.19 is an incredible distance. 00:11:51.15 That would allow you to reach the Perseus cluster, which is pretty far from Earth. 00:11:56.18 So, now we've talked about the amazing growth potential and the sheer abundance of viruses 00:12:03.01 on this planet, already these are two impressive ways of indicating that biological success 00:12:08.15 of viruses is just amazingly impressive, but now let's look at something that's largely 00:12:13.09 hidden to view. 00:12:15.21 Biodiversity is something that's fascinated humans for a long period of time, probably 00:12:19.11 ever since humans have observed other organisms around them. 00:12:24.02 But there's an invisible kind of biodiversity on this planet, especially in the virus world, 00:12:29.02 that has only been seen relatively recently with the kind of tools and machinery such 00:12:32.23 as electron microscopes that let us glimpse these larger number of entities that surround 00:12:38.10 us on the planet. 00:12:40.16 The first thing to state is that viruses by no means are identical to one another in their 00:12:45.13 morphologies. 00:12:46.13 Some of them are amazingly complex, with beautiful body plans that almost look like a lunar lander 00:12:51.18 -- something incredibly beautiful, I would say, in nature, but often escapes our attention 00:12:56.23 because they are so small. 00:12:59.01 Other forms of viruses are more like tubes and beautiful icosahedrons, so there's an 00:13:05.12 amazing variety, but you'll notice that the line here at the bottom... 00:13:10.08 0.5 micron, which is 1/2000 of a millimeter... all of these body plans that I'm showing you 00:13:16.07 thus far suggest that viruses are submicroscopic. 00:13:20.14 And I would say that's an amazing amount of beautiful morphology, complexity, and biodiversity 00:13:26.08 that is also amazingly small in size, so I think that that's pretty impressive. 00:13:31.15 But there's a little quirk to viruses and the way that they had been isolated from natural 00:13:36.08 sources through time, that researchers actually missed the fact that some viruses are not 00:13:42.02 submicroscopic. 00:13:43.02 In fact, some of them are actually larger than the smallest-size cells. 00:13:47.19 So, newly discovered viruses, I would say, are macroscopic -- certainly when you consider 00:13:52.24 a virus like mimivirus relative to the size of an E. coli cell. 00:13:58.04 Here's something more typical of what someone would continue... would... would think of 00:14:01.16 as a typical particle size, and that would be HIV. 00:14:04.18 So, the point here is that by no means are all viruses submicroscopic. 00:14:09.16 Instead, some of them rival or exceed the size of cellular life. 00:14:14.08 Now, these mimiviruses did escape our attention through a little quirk of how people isolated 00:14:20.00 viruses from nature, putting them through filtration and assuming that anything that 00:14:24.04 passed through a very small pore size must be a virus, whereas everything that was held 00:14:28.15 back must be cellular or cellular debris. 00:14:31.23 But all one has to do is increase the pore size in these filtration experiments and you'll 00:14:37.08 find that some amazingly large-sized viruses are evident and still thriving on this planet. 00:14:43.14 So, you can go off the coast of Chile, for example, and within sea water you could find 00:14:48.04 these large-sized viruses. 00:14:50.07 It's also available to see them in ice cores in places like Siberia, where researchers 00:14:56.23 very carefully can take old material and bring it up to the Earth's surface, some 30,000-year-old 00:15:03.10 ice cores have been brought up to the Earth's surface. 00:15:05.12 And, within these, we see these large-sized viruses. 00:15:08.22 That alone indicates that large-sized viruses are certainly not anything new; they've been 00:15:13.18 around on this planet for some period of time and they merely escaped our attention through 00:15:17.21 quirks of methodology. 00:15:21.02 And the natural history study of viruses is something that I would say is certainly thriving. 00:15:26.19 There are entire research programs that can go into places like Yellowstone Park in the 00:15:31.09 USA, where there are certain extreme environments, especially hot springs, and one can look for 00:15:37.07 viruses that are infecting some of these extremophiles. 00:15:41.14 And it's very easy to find that these viruses are completely new to virus family classification. 00:15:49.08 We see body forms and, ultimately, when one characterizes these viruses through genetics, 00:15:54.12 they are not at all closely related to other virus families that have been described in 00:15:58.16 the past. 00:15:59.16 So, I would say that natural history is alive and well in virology, and it is possible to 00:16:04.16 go out and very easily, in nature, isolate material that shows you very new viruses that 00:16:10.09 are entirely new to the biological classification. 00:16:14.00 Adaptability... so, this is the ability for organisms to interact with their environment, 00:16:21.04 to undergo selection to become better adapted through time, so that they create a better 00:16:26.00 match to their environment. 00:16:28.06 Darwin was the one who best articulated this through the process of natural selection, 00:16:32.15 so we know... we will now talk about how viruses have an amazing capacity, on average, to adapt, 00:16:38.05 and this certainly contributes to their biological success on the planet. 00:16:41.18 So, Darwin had a way of explaining natural selection that was beautifully elegant. 00:16:47.07 Essentially, if you have these four components, you could think of natural selection occurring 00:16:51.15 in any biological system with inheritance, no matter whether it's on Earth or when we 00:16:56.12 ultimately, probably, will discover life elsewhere. 00:16:59.01 So, if the individuals in a population vary from one another, and if that variation is 00:17:04.12 heritable -- if it could be moved across generations -- one can expect that some of those variants 00:17:09.21 are going to be better advantaged than others in surviving or reproducing, according to 00:17:14.01 whatever the details are of the environment or the ecology that they... that they experience. 00:17:19.05 So, ultimately the population should change genetically, or evolve, to reflect the ones 00:17:26.21 that are the most successful variants. 00:17:29.03 And if all of this is in place, then evolution by natural selection can occur. 00:17:33.24 Darwin best articulated this idea in his most famous book, On the Origin of Species. 00:17:39.23 A great example of this comes from the virus world, where HIV is of course a very important 00:17:46.02 biomedical problem that humans face, HIV that can ultimately progress to AIDS through infection. 00:17:53.00 But not too long after the AIDS epidemic occurred there was a wonder drug called AZT that people 00:17:59.22 thought would be the thing that would just eliminate this problem. 00:18:04.19 Without going into the details, the ability of AZT is to disrupt HIV's capacity as an 00:18:10.23 RNA virus to enter a cell, replicate to turn into a DNA form that inserts into the genetic 00:18:17.18 material, and then exits the cell again as RNA. 00:18:21.00 And this lifestyle in viruses we call a retrovirus. 00:18:25.24 So, here's the problem with treating HIV as an RNA virus that has an amazing mutational 00:18:33.00 capacity with only a single drug. 00:18:35.18 Ultimately, we would expect that drug to fail and unfortunately we only observed this when 00:18:40.15 AZT became popular and used as a drug, and it was seen to widely fail through time. 00:18:46.00 So, through mutation, virus populations can change, especially RNA viruses, which have 00:18:52.13 no ability to correct the errors that just simply occur in the replication process. 00:18:58.16 In this diagram, you see how an infection could begin with a HIV population that is 00:19:04.06 identical to one another, and would be entirely susceptible to AZT. 00:19:09.20 And through time, because of this error ability in the virus population, you are going to 00:19:15.18 have partially resistant or fully resistant forms of the virus simply show up, and these 00:19:21.23 would be resistant to AZT, either partially or completely, as shown in the diagram. 00:19:27.05 And importantly, keep note of this: all of that variation occurs before any AZT is brought 00:19:35.12 into the human patient. 00:19:37.02 So, ultimately, what happens is very similar to what we see with evolution by natural selection 00:19:43.12 -- in fact, it's identical and it's a great description of it. 00:19:46.02 The individuals vary, the variation is heritable, some of those variants are advantaged when 00:19:52.06 AZT eventually is the ecological challenge that the population experiences, and then 00:19:58.07 ultimately those variants take over the population, or it evolves, so that the entire population 00:20:04.23 has escaped AZT as the drug that would ordinarily, we would hope, control it. 00:20:09.21 So, unfortunately, this was observed in every single patient who was administered AZT. 00:20:14.13 It either happened very early on if those mutations occurred early, or later on, if 00:20:19.11 they just happened to occur later. 00:20:21.06 But ultimately, the unfortunate outcome is that AZT always failed. 00:20:27.02 HIV and other disease scourges of humans that are caused by virus... virus infections are 00:20:34.17 not new. 00:20:36.02 Many of them we can find evidence of having occurred in human populations long ago. 00:20:40.18 When one looks at hieroglyphics, mummified remains, artwork from older populations of 00:20:47.03 human from ancient times, this reveals the antiquity of virus diseases. 00:20:52.01 For example, this man, shown in a heiro... in a hieroglyphic from ancient Egypt around 00:20:57.00 3700 BC, has a very characteristic clubfoot that's associated with poliovirus infection 00:21:05.08 that entered in the gut, like all polio viruses ultimately do, but then sometimes poliovirus 00:21:10.18 moves to your neural system, and it can disrupt your normal development and lead to limb deformities. 00:21:16.13 So, this man is definitely showing a characteristic deformed limb of a poliovirus infection. 00:21:24.21 Smallpox is another old disease of the human population, and this artwork is showing an 00:21:30.18 unfortunate person suffering from a smallpox infection, which would be ultimately lethal. 00:21:36.15 And, fortunately, we don't worry about smallpox anymore because there was a global vaccine 00:21:41.04 campaign that eliminated it as a natural thing that would infect humans, but the point is 00:21:46.14 that we can find, through this ancient material that humans and older populations have left 00:21:51.09 behind, that humans have been suffering virus diseases for a very long time. 00:21:56.03 I would assert that, probably, this has happened as soon as humans evolved as a species on 00:22:01.11 the planet, there would be viruses that would challenge their health. 00:22:05.07 So, I'd like to end with talking about the impact, in general, that viruses have on other 00:22:10.13 organisms on this planet, and this is really quite profound. 00:22:15.21 Similar to the examples I just covered for smallpox and HIV, etc, there are many diseases 00:22:23.03 that humans face that are a challenge to our health and our mortality, and a lot of these 00:22:28.08 are endemic problems, for example, the parasite that is transmitted by a mosquito and causes 00:22:34.20 malaria in sub-Saharan Africa and other tropical regions. 00:22:38.07 This has been around for a very long time -- that happens to be a eukaryote -- and you 00:22:41.24 could see the response, even in our genetics, of ways that we would be naturally better 00:22:47.06 able of fighting off malaria, and it has contributed to ways that the human population has changed 00:22:52.10 genetically through time. 00:22:54.03 But that's different than an epidemic that is highly deadly and rises in frequency very 00:23:00.24 quickly, and impacts a lot of, in this case humans, through mortality, something that 00:23:06.08 happens very quickly. 00:23:07.13 So, here are four examples, and I'm highlighting, in red, that three of them were due to viruses, 00:23:13.23 virus illnesses. 00:23:14.23 So, the Spanish influenza of 1918, amazingly, before humans were traveling around the world 00:23:21.11 through flight, through commercial flight, still 50 to 100 million people around the 00:23:26.13 world contracted influenza and died from this highly virulent form of the virus. 00:23:33.24 More recently, the HIV/AIDS epidemic that started around 1981 is something that has 00:23:38.15 unfortunately left roughly 35 million people dead and many, many more than that are infected. 00:23:44.01 Fortunately, we have new ways, things other than AZT, that keep people alive for a long 00:23:48.22 period of time when they're HIV-infected, but certainly during the early part of that 00:23:53.05 pandemic we saw a high degree of human mortality and we still see it today. 00:23:57.20 Now, it's hard to put exact numbers on the New World smallpox epidemic, around 1520, 00:24:03.11 when this started. 00:24:04.18 This is when Europeans came to the New World, interacted with Native American populations, 00:24:09.21 in some places displacing them, and they introduced into those populations smallpox, something 00:24:16.08 that Native Americans had not seen. 00:24:18.09 So, this was experienced as a highly virulent illness in Native American populations. 00:24:24.02 It's unclear how many people died because we just don't have accurate records of how 00:24:27.12 many people were in these populations at the time. 00:24:30.00 Certainly, this could have been on the order of the two pandemics that I listed above. 00:24:36.07 And last, I will remind you that some bacterial illnesses also have the capacity to have huge 00:24:42.22 impact on human populations. 00:24:44.20 The "Great Plague" in Europe in the middle of the 1300s was something that left in its 00:24:49.06 wake some 28 million people, or roughly 40% of the European population succumbed during 00:24:55.09 the Great Plague. 00:24:56.21 It's a little controversial how this bacterial illness could account for that amount of mortality. 00:25:03.09 Some people believe that the sheer poor living conditions that people experienced at that 00:25:07.10 time left them highly vulnerable to something like virus illnesses, as well, that might 00:25:12.16 have contributed to those millions of people who died. 00:25:15.00 So, again, we're a little uncertain there, but for the most part these examples are grim 00:25:20.05 ones of how impactful viruses can be in terms of mortality. 00:25:24.10 So, I don't want to leave you with all bad news about viruses, because, certainly, there 00:25:29.15 are a lot of viruses that positively impact other organisms, including humans. 00:25:35.18 So, let's begin long, long ago, some billions of years ago when the cyanobacteria appeared 00:25:41.14 on this planet and they started to thrive through evolving photosynthesis, that, 3 billion 00:25:47.21 years ago or more, this changed the Earth's atmosphere so that 50%, today even, of the 00:25:54.16 Earth's oxygen is due to photosynthesis that comes from cyanobacteria living in the ocean. 00:25:59.23 And if they hadn't evolved long ago and changed the average amount of oxygen in the atmosphere, 00:26:05.18 it would have been impossible for large-bodied organisms like us to even evolve in their 00:26:09.21 wake. 00:26:10.21 So, we can thank the cyanobacteria for that. 00:26:13.22 But there's an interesting thing that most people don't know and that is cyanobacteria 00:26:18.23 undergo a lot of mortality from cyanophages. 00:26:22.12 These are viruses that live alongside them in the ocean and they outnumber the cyanobacteria 00:26:28.18 and they thrive on the cyanobacteria, essentially as resources. 00:26:32.24 But there was an interesting finding not long ago that these cyanophages have genes that 00:26:38.18 allow for photosynthesis to occur. 00:26:40.24 And that was a very strange discovery, because we know that viruses don't undergo metabolism. 00:26:46.18 What would they be doing with photosynthesis genes? 00:26:49.10 It starts to make more sense when we think about the virus life cycle and the necessity 00:26:53.19 of keeping the cell going and churning through its metabolism, so that viruses can undergo 00:26:59.15 proper replication. 00:27:00.23 Therefore, it's not surprising that they bring these genes into the cell with them, so that 00:27:06.01 those processes can occur. 00:27:08.08 But a factoid I'll leave you with is that perhaps 5% of the breaths that you'll take 00:27:13.03 today ultimately come from those genes that are on cyanophages, rather than any other 00:27:18.12 source of oxygen. 00:27:21.20 We are more and more familiar with microbiomes -- you hear more and more about this in the 00:27:26.04 news. 00:27:27.04 So, these are the fungi, the bacteria, and the viruses that live on and in macroorganisms 00:27:31.23 such as humans. 00:27:33.14 And it's really interesting how these communities vary, even through locations in our body. 00:27:38.24 Inside and outside, you have different communities of these microbes thriving on and in your 00:27:43.08 body. 00:27:44.08 Well, the same thing goes, but different composition of those communities exists, for animals, 00:27:50.01 plants, and other macroorganisms on the planet. 00:27:53.13 Some of these we keep in our homes or we rely on for food, so it's important to think about 00:27:58.11 how these interactions are occurring with organisms that are essential to us, or that 00:28:04.15 simply give us pleasure, like as pets in our home, they have their own characteristic microbiomes 00:28:09.07 that we're learning more and more about. 00:28:11.19 And I should also emphasize that, certainly, all wild animals and also wild animals that 00:28:17.13 we rely on for food, they have their own characteristic microbiomes too. 00:28:22.13 So, viruses in your microbiome... you hear in the news about how the microbiome is probably 00:28:30.12 the thing that is causing certain traits in humans, making... making us more disease-prone 00:28:35.24 or disease-averse, so you'll hear a lot more about this in the coming decades, but you 00:28:41.13 actually don't hear that much about your virome, the component of your microbiome that is the 00:28:46.11 viruses. 00:28:47.14 There was a neat discovery recently that, perhaps, these viruses that exist on and in 00:28:53.07 your body are interacting with your body to make you healthier. 00:28:56.19 This diagram is showing how phages, which cannot infect our cells, can interact with 00:29:03.06 the mucus layers that we naturally produce that help protect us as a barrier from bacterial 00:29:08.16 infection. 00:29:09.22 Interestingly, these phages will interact with the mucus layer and be oriented in a 00:29:15.11 way such that their tail fibers are able to interact with any bacteria getting to the 00:29:20.05 mucus layer and trying to transit through to get to your cells. 00:29:23.21 This provides an extra barrier that protects you against those bacteria, because the phage 00:29:29.03 will attach, replicate, kill the bacteria, exit the cell, and more of those infection 00:29:35.10 events can occur. 00:29:36.19 This is certainly to our benefit, but we have a lot more to learn about whether this is 00:29:40.20 something that has been an... an adaptation that evolved for these phages to interact 00:29:46.03 with macroorganisms to do this, or whether they're simply taking advantage of the fact 00:29:50.11 that phages are everywhere, sometimes they are in the correct place for this to happen. 00:29:57.19 So, a final thing that I'll leave you with is that the human genome project gave many 00:30:04.13 surprising results, but there was a very surprising one in terms of, if you look at our DNA com... 00:30:09.24 our... our... our DNA chromosomes, you'll find a nice match between roughly 8% of your 00:30:16.15 human DNA seems to be viral-derived. 00:30:19.19 And one might ask, well, how is that possible? 00:30:22.17 You can think of this as the ghost of infections past. 00:30:25.08 In our long ago species ancestors that led to humans, ultimately, there were some virus 00:30:31.17 infections that those organisms suffered and interestingly there can be viruses that avoid 00:30:39.10 detection by their hosts because they have special genes that make them hide, so, essentially, 00:30:45.17 what has occurred in the evolution of placental mammals is that we could not have existed 00:30:50.06 on this planet unless, long ago, our ancient ancestors had undergone these virus infections, 00:30:57.21 and those genes, instead of becoming deleterious and helping viruses avoid detection by our 00:31:03.22 long ago ancestors, instead they were genes that were co-opted and taken into our genome, 00:31:09.15 and ultimately helped placental mammal mothers not reject the baby in the body. 00:31:16.05 And this is an amazing thing due to what are called syncytian proteins and genes that come 00:31:20.01 from viruses. 00:31:21.14 This is clearly a way that virus genes can be highly useful to other organisms and, in 00:31:27.18 fact, there's no way that you would be sitting here listening to me give this talk unless 00:31:32.02 these ancient infection events had occurred, and had led, ultimately, to the evolution 00:31:36.15 of placental mammals. 00:31:37.24 So, I've covered a lot of evidence for what we would say indicates that viruses are the 00:31:45.16 most biologically successful entities on this planet. 00:31:49.12 If you look at their growth potential, their abundance, and their biodiversity, they simply 00:31:54.15 outnumber, and can grow faster, and produce a larger number of forms than any other organisms 00:32:02.02 that we know of. 00:32:03.19 In addition to that, they can interact with other organisms in their environment, and 00:32:08.01 have an amazing capacity to adapt to environmental change, which I find completely fascinating 00:32:13.12 because, essentially, viruses cannot control where they go in the environment, and yet 00:32:18.13 they can encounter environments that are challenging to them and improve through time through adaptation 00:32:24.12 by natural selection. 00:32:26.00 Ultimately, their impact on the rest of the biological world is profound and immense, 00:32:32.12 and literally we thank viruses for some genes that they have devoted and given to us in 00:32:38.03 our genome, and this is something that's clearly impacted -- positively -- the human species 00:32:44.16 through time.