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.