THE SYMBIOTIC DEPENDENCY OF LIFE, THE VIRAL DIMENSION
I studied and taught comparative anatomy for many years. My students were often surprised that we studied the anatomy of other animals alongside that of humans. A few students would raise their hands and ask why they needed to study sharks (for instance) when it was humans they were interested in. There is a good reason why comparative anatomy requires a consideration of fish (and all other kinds of life) alongside human beings. It turns out that we can trace separate organs, like the liver or immune system, through their own evolutionary history—one that is independent of the creatures that carried them. In a sense the organs can be considered as populations of cells with particular functions. The mechanical workings of specialized organ cells are controlled by genetic information that has been passed down a long line of descent from ancestors who carried similar organs. In this sense organs transcend time and species.
Our organs are ancient; the earliest fishes had livers, and those livers functioned much like the ones we have in our own bodies. No matter what our subject—shark, bird, human—my students quickly realized that each individual is a collection of organs, all of which are related along lines of descent. Liver cells, for instance, function with surprising similarity from species to species. It turns out you can compare a shark liver and a human liver and that they do pretty much the same thing.53 This is a significant realization; it tells us that on a biochemical level these systems have been in place for a long time (just like bacterial photosynthesis). Our bodies are just a collection of these different systems.
I’ve been thinking about this since my undergraduate training in comparative anatomy, but since that time there has been a growing acceptance of symbiosis in related fields, such as evolutionary biology. In the last chapter we saw how bacteria have formed a symbiotic association with us, living alongside cells of our own digestive system to create a microbiome. This community of different populations with different genomes evolves together and reveals a long biological predisposition for coexistence. In this chapter we will see how a similar type of symbiotic relationship exists also inside us, with a population commonly viewed as “sinister”—viruses.
Microbes such as bacteria and algae are distantly related to us, and understanding their way of life is more an exercise in imagination than in empathy. In general these organisms circulate freely throughout all aquatic environments, and many nonaquatic places as well, moving with the currents and winds, thriving on surfaces that meet their conditions of existence. Inside the tiny fluid-filled spaces between your bones, caked on the insides of pipes and air vents, floating freely in the oceans—colonial and solitary—bacteria are everywhere and their activity has changed little in billions of years.
Even though we cannot visit the primeval Earth or the original habitat of bacteria and other microbes, our imagination has some help in conjuring up their existence. National Geographic—both the magazine and the eponymous TV channel—allows us to see up close the remote and microscopic niches that bacteria and algae love. From deep-sea vents in the middle of the Atlantic ocean that spew out poisonous gases and molten magma, to briny intertidal mudflats baking in the sun at 100+ degrees Fahrenheit, to the icy outcrops on glacier-encrusted mountaintops, these Technicolor images reveal the world’s loneliest places, where we are shown the evidence of bacterial and algal life. Even if we find it difficult to empathize with the experience of individual bacteria or colonies of algae, we can certainly get a grasp on the inhospitability of their habitats.
Viruses, however, live in an ecological niche that is so alien to us that it’s utterly impossible for a human to experience anything like it. Viruses are completely alien to us: Viruses don’t make their home in the fluids or watery environments of Earth, or on surfaces or biofilms or anywhere at all that we usually associate with the biosphere.54 Instead viruses live in the intracellular molecular milieu that only the most specialized scientists have an opportunity to witness.
If recent estimates are correct, there could be as many as 100 million virus varieties currently living among and within us. They are rather simple to describe, but difficult to see because of their size. They are on the scale of only tens to hundreds of nanometers (a nanometer is 1/1000 of a micrometer, which is 1/1000 of a millimeter). Only the most technologically advanced laboratories have equipment that is sensitive enough to view them with electron microscopes. They consist of a capsule—think of it as a very tiny pill capsule—filled with a small number of genes necessary for the replication and synthesis of proteins that pervade the capsule. These proteins are used to bind with host cells. When an infection occurs, viruses attach to the cells of the host. At this point the host cell either ingests the virus completely (a process called phagocytosis; more on this later) or the virus might remain on the outside, but in both cases genetic material is shared; the genes of the virus are fused with the genes of the host in the nucleus of the cell.
Viruses are not self-sufficient replicators; they must make their homes within other cells. Unlike bacteria, which can live their lives free-floating in water because they have all the necessary cellular “machinery” to survive, a virus must find a host cell to complete its life cycle. If the virus fails to find one it becomes—to all intents and purposes—an inert complex molecule that dies without passing along its genes to the next generation. A virus that successfully finds a host cell, however, zeros in on the DNA found inside the host’s nucleus. It is here that viral genes fuse with the genome of the host and thereby cause the host’s genetic machinery to produce more viral products. After hundreds of clonal viral copies are made, the host cell usually dies and bursts open. This releases the new daughter viruses into the surrounding environment, which begins a new generation of parasitic infection.
Think of millions of infected cells in your nose and throat during a cold or flu, for example, each producing hundreds of new viral particles and then dying every hour, releasing the daughter viruses into your runny nose and saliva. It’s easy to understand how the viral parasite population grows so rapidly, and why it so quickly overwhelms your healthy tissue. Sneezing, coughing, or sharing body fluids spreads them to others, where the viral population finds more healthy tissue to infect and continues to increase.
The flu and the common cold are familiar examples of a detrimental viral infection. In other cases, however, viruses do not induce replication in the host cell. Instead they use the host for temporary storage of their genetic material. The host can usually undergo normal operation without hindrance in such cases, even though it has incorporated the viral genes into its own DNA.55 It’s almost as if the virus went only halfway, infecting healthy cells but then resting after it successfully fused its genes into the DNA of the host. Sometimes, perhaps from an environmental trigger, the benign, resting parasitic genes become active again, causing a harmful effect that brings about viral replication. But there are instances where this resting phase has become permanent in host populations. In fact, sometimes it can be beneficial.
One benefit we humans get from viral genes is found in our ability to digest starch. Amylase is an enzyme protein present in saliva. It helps break down carbohydrates in the mouth, converting them to sugars as we chew during the first stage of digestion. The genes that produce amylase are active in the specialized cells of our salivary glands and in our pancreatic tissue. Scientists discovered that a particular viral gene sequence (known as a retroviral one) is embedded in our chromosomes that is responsible for activating the production of amylase in the salivary gland and pancreas.56 The implications of this finding are profound. They show that at some time during primate evolution, a viral symbiosis took place with our evolutionary ancestors that allowed us to digest starch. Far from being a nasty parasitic infection, this symbiosis turned out to be beneficial because it allowed us to broaden our diet. Such flexibility during times of drought or highly seasonal food availability must have been highly favored by natural selection.
Researchers believe that such beneficial virus-host symbioses are common in the animal kingdom, and that their high selective value allows them to persist for many millions of years.57 Furthermore, over these vast periods of geologic time, the viral components of genomes, sometimes called the “viral load,” may continue to increase because there is no downside to the symbiotic relationship. In other words these viral symbioses are so favorable to natural selection that the viral load can be considered a permanent fixture of many plant and animal groups. Without its high affinity for genetic fusion, a viral particle would be just an innocuous bystander in the pageant of life.
Some scientists claim that since viruses don’t have a self-replicating ability they aren’t “alive.” Calling them nonliving seems to miss a crucial point. They may be unfamiliar to us, but they still have the potential to replicate, and replication is an important factor when we talk about populations. Evolutionarily speaking, for instance, your replicative potential is the only thing you’ve got that matters. With respect to evolution, your accomplishments, your beliefs, and your ideas mean nothing compared with whether you succeeded in passing on your genes to your offspring and helped them raise successful progeny of their own. We are evolutionarily inert if we don’t have children. If you choose not to reproduce, then, as far as evolution is concerned, you cease to have any relevance.58 Humans may debate about the wisdom and implications of reproduction, but viruses feel no such qualms. Viruses are full of replicative potential themselves, and they provide benefits to their hosts in many cases, so we should consider them an important player in the evolution of all populations.
The year 1964 was a great one as far as I’m concerned. It was the year I was born, though little did I know the magnitude of the globally significant events taking place outside my crib in Madison, Wisconsin. This was the year that the genetic code was finally sequenced after a decade of laborious experimentation. This code is the same for all organisms and viruses. Remember, the “code” is simply the letters and their meaning. The difference between species is not in the code, but rather in the way the code is sequenced. Genetic sequences are written out as a long list of letters, each one corresponding to a particular molecule.59 The sequence of these molecules, called nucleobases, is different in every species.
After 1964 there was a great deal of interest in finding the DNA sequences of various species to discover just how different each species was from one another. Genetics became a hotbed of research, particularly in efforts to determine if variation at the genetic level (in the sequence of nucleobases) was linearly correlated with phenotypic variation (the varieties of forms visible to the naked eye). This quest led eventually to the development of whole-genome sequencing, which consists of the precise ordering of tens of millions of nucleic acids, and could not have been accomplished without the advent of powerful computers. (The human genome was fully sequenced in 2001.)
Perhaps the most astounding thing we learned about the human genome is the fact that we are not as unique as we like to imagine. The genomic difference between humans and our closest relative, the chimpanzee, is only around 1 percent. That means that roughly 99 percent of our genes are the same as chimps! This would have pleased Charles Darwin greatly. He spent much of his life dealing with people who were outraged by his claim that the great apes and humans came from a common ancestor. People who have a problem with the idea of being related to apes will have an even bigger difficulty with another discovery that came from the deciphering of the human genome.
About 8 percent of the human genome is derived from a particular class of virus mentioned before, called a retrovirus.60 Another 34 percent mimics viruses that have been inactivated (or possibly just resting, as described earlier), and about another 3 percent has a probable viral origin. Add it all together and almost half our genome is viral. Most of these sequences have been handed down to us from our mammalian forebears. The retroviral component of our DNA alone accounts for a larger portion of our genome than the part that specifies all the proteins necessary for our growth and survival.
The mammalian genome has been under almost constant infection by viruses since the origin of the group more than 200 mya. In that time there have been many instances of benign symbiosis, and as outlined above, in some cases benefits conferred in the coevolutionary process. Another word that describes this fortuitous relationship is “endogenization.” We say that a viral genome has become endogenized when it is inserted into the DNA of the host’s sperm or eggs.61 In such an instance reproduction provides the mechanism that allows the infection to pass through time, from one generation to the next. Millions of years later the descendants of the original host are still carrying copies of the original viral infection. Since humans are a late arrival on the planet—our genus, Homo, is roughly only 2.3 million years old62—we inherited more than 197 million years’ worth of viral infections from our mammalian ancestors.
Only about 1.5 percent of our genome is composed of genes that actively produce the proteins involved in building our skeletons, making blood, producing other organs, and all the other things essential to keeping us alive. If you’ve been keeping count, you see that nearly half of our genome is unaccounted for. Scientists are unsure about its function. Neither active genes nor viral DNA, much of this genetic material may be involved in coordinating the timing of “turning on” genes to make proteins, or “turning off” genes during embryonic development. Some such “control regions” of the human genome are well known already, but there will likely be many more discoveries about how they, and possibly other ones, function.
In order to appreciate viruses, we have to take into account these recent discoveries. In no way do I mean to convince you that we should view viruses with sympathy—to do so would go against my belief that we must view life starkly without regard for sentimentality63 if our goal is to solve population problems. But first exposure to viruses is usually negative. Each of us has had the flu, probably first acquired when we were very young. The Influenza virus is probably the most familiar of all the viruses. So it’s only natural that the public perception of viral coexistence would be negative.
What I’ve been presenting in this section, however, is less well known, but ever so important to understand because viruses are unique partners in our evolution and in our daily lives, and they have a lot to teach us about coexistence with perceived enemies. Every cell of our body is laden with viral genes. Our cells are of a type known as eukaryotic. Every familiar organism, from plants to animals—even to the lowly paramecium—is composed of eukaryotic cells. The fundamental property that distinguishes these cells from those of prokaryotic cells (that is, bacteria) is that eukaryotic cells contain a complex organization of organelles (tiny organs) while prokaryotes are devoid of them. Each organelle provides a specialized function in the life of a eukaryotic cell.
Bacteria are not so complex. As we saw in the last chapter, they are more one-dimensional in their function. All bacterial cells have an engine-like mechanical function. When this function is active, it can convert chemicals from its surroundings into other chemical compounds and derive some energy for itself in the process. Prokaryotes don’t have organelles, they simply carry DNA (not contained in a nucleus) diffusely floating in cytoplasm along with a few other simple parts that provide a metabolic function.
Almost all the life on Earth can be lumped into these two great big categories: those that are prokaryotic, such as bacteria, or those that are eukaryotic, such as animals, plants, or algae. It’s taken a long time to figure out that eukaryotic organisms could not exist without the close symbiotic relationship with prokaryotes (for example, bacteria in human guts). This relationship goes back to the earliest days of life; the first eukaryotes were a symbiotic union of two different prokaryotic cells.64 This union formed a chimera—an organism composed of more than one genetic set of instructions. So if eukaryotic organisms are at root chimeras, then we know that our own bodies are made up of cells carrying genes that were handed down by preexisting ancestral species. Some of these symbiotic unions took place roughly 1.6 billion years ago at the very dawn of eukaryotic life.
Our genetic material is located in the nucleus of each cell in our bodies. You’ve probably seen a nucleus in a grade-school biology lesson—the teacher cuts a razor-thin sliver of an onion, drops a tiny amount of iodine on it to add color, and the cells that make up the onion become stained. The cell walls and organelle membranes absorb the dye and, once it’s your turn to look through the microscope, you see a dark central zone that is itself surrounded by a round darkened membrane, surrounded by a squareish cell wall. The cells abut one another and form a sheet of continuous onion tissue. The circles in each square are nuclei, and the dark-stained centers are the genetic material. It’s these nuclei that characterize all eukaryotic cells.
If you graduate to a more detailed course in microbiology, you’ll get a chance to look through better scopes and use better dyes. These special stains let you see other ovoid organelles inside eukaryotic cells. These are the mitochondria, much smaller than the nucleus, but much like it in the sense of its origin—their ancestors were free-living bacteria that underwent an endosymbiotic union and now exist as an essential part of a chimeric organism, the cell. It is crucial to recognize this chimeric quality of all eukaryotic cells,65 and as we will see it involves viruses as well.
Viruses are everywhere, yet they are neither eukaryotic nor prokaryotic in nature. They simply don’t qualify as cells. They are, however, replicators, just like prokaryotic and eukaryotic cells. This means that they are able to reproduce and pass on their genetic material to the next generation. Viruses, however, are obligate parasites, which means that they cannot pass on their genes, or make more of themselves, without using another organism’s reproductive machinery, as mentioned earlier. This hereditary mechanism gives them an eternal quality: They will be passed along from generation to generation.
Free-living viruses are, to borrow an earlier phrase, evolutionarily inert, unless they find a suitable host to infect. Luckily for viruses they are very good at attaching themselves to a host. The human influenza virus, or “the flu,” is spectacularly successful because its particles are expelled when already infected people sneeze or cough. These particles are minute—far too small to see—and so light that they are unaffected by gravity. Instead they float through the air, like sediments in a fast-flowing stream, never touching the ground surface because gravity is not strong enough and their mass is too small to be brought down to rest. When we inhale we suck the viral particles into their preferred oral or nasal habitats, where they attach to the mucous membranes that line our mouth, nose, and lungs, and release enzymes that allow their genetic material to pass into and mingle with the cytoplasm of our own cells. The “body” of the virus,66 if you wish to call it that—it’s really just a capsule—doesn’t penetrate the membranous barrier of our nasal, or oral, or pulmonic epithelia. In a sense the viral capsule is sacrificed, expelled as waste by the host, and only the genetic contents are transmitted.
Once the virus’s genes are successfully inserted into the host, they quickly attach themselves, by a variety of specific enzymatic reactions, into the already-fully-functioning DNA of the host. In other words, there is no longer any trace of the original viral particle, except in the genome of the infected organism that now carries the viral DNA. The infected person quickly starts to feel the effects of the flu because her cells are not functioning normally. Her metabolism is now impaired by the encumbrance of the viral load. The virus uses the human’s cellular mechanisms to make copies of its genes inside the infected cells, to build new capsules that carry the reproduced viral DNA, and to cause cellular activities that are not part of the host’s usual healthy functioning. The result? In the case of the flu, the infected person gets really, really sick. The virus needs bodily fluids—snot, phlegm, or diarrhea—to leave the body and find another host. The host’s malfunctioning organs and membranes oblige, generating streams of fluid. This makes her life wretched but allows the virus to leave in search of new fertile habitats—that is, more uninfected bodies.
The departing virus takes a souvenir of its host with it; most virus species have a membrane (aka the envelope) that surrounds the capsule (aka the capsid). This membrane is made of a bilayer of glycoprotein and lipids. When the virally infected host cell produces new viral particles, a fresh double layer of lipoproteins is created out of the membrane-building machinery of the host. In other words the offspring viral DNA67 is enclosed by membranes made by the host. Two different organismic sources (host and virus) produce one chimeric offspring.
In the life cycle of a typical virus-host interaction, the end result is a co-opting of the host’s ability to make copies of itself and produce cell products. Viral DNA gets incorporated into that of the host, and unwittingly the infected cells begin to make viral copies in the process of cell division, reproduction, and normal metabolism. This co-opting of cellular machinery can result in the budding of membranes from the infected cells—membranes that are produced by the host. Viral DNA can direct the actions of host cells to produce new membranes, surround copies of viral DNA inside the cell, and create buds that are ejected and sent out into the extracellular spaces. When viral buds are released, they become virions, or viruses in search of another host to infect.
The moment an appropriate cell surface is encountered, such as your nasal epithelium, for example, a virion attaches, releases its genetic material into the cytoplasm of the hapless host cell, and the process of viral co-option begins again. The host cell bears the infection by carrying the burden of viral genetic material. There is no competition, no war, just an automatic symbiosis whenever virus meets host.
Evolution is a series of intricate and complex interactions among living things, and viruses’ behavior is a great example of this. They nicely reveal one of the recurring themes of this book: All organisms are living proof of past symbiotic interactions and are simultaneously being influenced by new biotic interactions that will change them in ways we can’t necessarily anticipate.
At some point in the distant evolutionary past, certain infections seem to have become permanent fixtures of the biosphere, such as the beneficial viral infections mentioned earlier, or as we will see, the photosynthetic organs of all plants. While viruses themselves are good examples of symbiotic unions (the capsid membranes are produced by the host, and by genetic material from the “parent” virus), eukaryotic cells show an even richer history of symbiosis, one in which viruses also play a role.
Plants and animals are familiar to us, but their cellular anatomy is complex. If we look carefully at two basic types of eukaryotic cells, a generalized plant cell and a generalized animal cell, we see that both have significant differences, even though both are eukaryotic. These differences include that plant cells have a rigid cell wall made of cellulose carbohydrate while animal cells lack a cell wall; plant cells have pigments that absorb sunlight, while animal cells lack such pigments. But the most important difference for our discussion is that plants derive their energy from tiny organelles called plastids (chloroplasts, for example) while animal cells lack them and instead derive energy from organelles called mitochondria.
One similarity between plant and animal cells is the presence of a nucleus. It is inside this—the largest of all organelles—that the genetic material, DNA, is stored and sequestered when the cell is in its resting (nondividing) stage. The nucleus, mitochondria, and plastids of a eukaryote tell a fascinating story of chimeric evolution.
The eukaryotic cell is composed of more than one genome. That is to say the genes that it carries in its nucleus have a different evolutionary history than do the genes it carries in its mitochondria or plastids. The Russian biologist Dmitry Merezchkowsky first suggested, in 1905, that the eukaryotes had essentially evolved by an ancient symbiotic event so successful that it gave rise to all the various forms of eukaryotic organisms alive today. The late professor Lynn Margulis, of the University of Massachusetts at Amherst, revived this notion (having discovered it independently) based on more modern data in the 1980s, emphasizing the similarity between mitochondria and certain archaebacteria. In the 1990s James Lake at UCLA advanced the notion that the nucleus itself was the product of an ancient endosymbiosis, having originally been a free-living archaebacterium.68
Today there is little argument among microbiologists that endosymbiosis—the engulfment of bacteria by other bacteria—played a key role in the evolution of the eukaryotic cell. In fact it is referred to as the “endosymbiotic theory” of evolution, and it takes up a good deal of one lecture in the introductory evolution course I teach. There is considerable disagreement, however, as to which particular bacterial species were involved in forming the nucleus, mitochondria, and plastids.69 For now it is safe to say that the nucleus, mitochondria, and plastids of all eukaryotes each carry a different set of genes, which are leftover signatures of ancient symbiotic events.
When a cell divides, as happens over and over again during our growth, the nucleus makes copies of its genes, and they are distributed to daughter cells so that every cell in our bodies contains the same genetic material that was present at conception. There is no sharing of this genetic material with the mitochondria (or plastids in plants). The mitochondria that were present at fertilization (provided by the egg, i.e., from the mother) divide independently and contain their own suite of unique genes—originally from a certain primitive species of bacteria that belongs to the group called proteobacteria—and do not contribute anything to the nuclear genome of the host cells. The same is true in plants. The nucleus contributes its genetic contents only to the nuclei of daughter cells, whereas the plastids contribute to daughter plastids, and never do the two suites of genes commingle.70
So if eukaryotes are the product of a symbiotic event between two different prokaryotic organisms, this leaves us with a couple of puzzling questions with respect to this chapter: (1) Where do viruses, which are neither prokaryotes nor eukaryotes, come into play in the endosymbiotic evolution of eukaryotes? And (2) How does this relatively new, symbiotic worldview mesh with the more traditional doctrine of competition-based evolution?
We will leave this second question for another chapter.
But to answer the first question: There are something like 100 million species of virus on our planet, and many if not most of them infect only bacteria. As mentioned earlier, these viruses are known as bacteriophages. A bacteriophage virus injects its genetic material into a bacterium, and the genes of the host are mingled with the genes of the virus. The cellular machinery kicks out copies of the viral DNA and packages it into tidy little capsules that are ejected from the cell (often at the expense of the cell; it succumbs to the infection), and the new viral particles (daughter virions), part viral (genes), part host (membranes), are released to an unsuspecting population in search of more infectious activity.
The fusion of viral DNA and host DNA led microbiologists to consider a possible role for viruses in the endosymbiotic theory of evolution. If bacteria were engulfing other bacteria in the Precambrian, forming endosymbiotic unions, leading to a more complex type of cell (eukaryotic), this might have been a good defense against bacteriophages. In other words, what better way to protect yourself from viral attack—which occurs following the virus’s “recognition” of proteins on the cell membrane surface of the host—than by taking refuge inside a different species?
Viruses filled the Precambrian oceans, looking for potential hosts to infect. This still happens; free-floating DNA viruses (called mimiviruses) roam our oceans, and like bacteria, they have probably been floating in all kinds of watery environments since the earliest phase in the history of the biosphere.
Perhaps it was in the open ocean that another unlikely but highly adaptive event occurred: Free-floating viral DNA became incorporated into the cytoplasmic space of another free-floating unicellular organism, something akin to a red alga. In other words the origin of the eukaryotic nucleus was, in simplistic terms, a virus escaping from a free-floating life stage where it was under constant infection by other viruses—to a coddled existence inside another cell (such as a red alga).71
The nucleus itself, then—the defining characteristic of all familiar organisms72—can therefore be thought to have a viral origin. Consider these facts: Viruses can disintegrate the membrane of other cells and reassemble it, just as we see in the nucleus during eukaryotic cell divisions. The nuclear membrane disappears during metaphase and is reassembled during telophase in the growth and maintenance of all familiar organisms. This implies that viral genes are involved in genetic replication during cell division of eukaryotes—a fact that has been confirmed by molecular biologists.
Perhaps most intriguingly, viral genes are directly involved in the transposition of eukaryotic genes during cell divisions. In other words viruses assist “jumping genes” in eukaryotes. This phenomenon—in which segments of DNA get transposed from one chromosome to another—is one of the most significant sources of genetic variation in familiar organisms. And as we already know, evolution is not possible without genetic variation. If you look at life this way then viruses are crucial to all eukaryotic organisms.73
Evolution of familiar species including humans involves viruses from the Precambrian oceans. Today’s viral diseases can be seen as more recent phenomena, patterns of coexistence that are still being worked out. The ancient infections have evolved over hundreds of millions of years and are now part of us, sequestered in our chromosomes. They can now be considered symbioses.
Some people find the idea that viruses played—and continue to play—a part in the ongoing evolution of life distasteful. Who wants to be related to the flu? These people might argue that prokaryotes—bacteria, for example—eventually evolved into eukaryotes and that viruses were equally infectious to both. There is evidence, however, that viruses were more benignly intimate with eukaryotes. Let’s look at the enzymes that help repair and replicate genetic material, as well as the protein that forms the “skeleton” inside eukaryotic cells (a protein called tubulin). The polymerase molecules, DNA polymerase and RNA polymerase, as well as the protein called tubulin, are crucial to the proper functioning of all eukaryotes. The polymerase enzymes work to assemble new chains of DNA and RNA during cell division, and the tubulin protein acts as a scaffolding upon which chromosomes assemble and get pulled apart during the formation of daughter cells during replication. These elements of eukaryotic cell division can be found in viruses, but prokaryotes have their own rudimentary polymerases—unrelated to those found in viruses and eukaryotes. Tubulin is not found in prokaryotes at all.
Given this information,74 it is unlikely that prokaryotes “evolved into” eukaryotes during the early days of cellular life on the planet. However, it’s equally unlikely that viruses “started the evolution of life,” because they are completely dependent on other life for their existence. The only logical conclusion is that all organisms today have a symbiotic dependency on other life forms due to the interactions of the simplest single cells, free-floating viruses, and organic molecules (building blocks) of the primeval oceans. Those relationships that were formed at the earliest phase of the biosphere are essential to the functioning of the biosphere. We cannot escape these interactions. The vestiges of those ancient symbioses are readily observable in ourselves and in all organisms with whom we coexist.
The origin of the eukaryotic cell is most likely a three-part drama that took place hundreds of millions of years before any kind of complex life arose on the planet. First came the endosymbiosis of mitochondria (proteobacteria infecting another unicellular organism), then the endosymbiosis of plastids in plants and protists (cyanobacteria infecting cells that had already evolved with enclosed mitochondria), and finally the endosymbiosis of the nucleus (a large mimivirus-like virus infecting an alga with plastids and perhaps a separate infection of plastidless cells with mitochondria). All three acts were symbiotic in their style. This means no competition, no warring factions, no individuals maintaining a dominance over other individuals, but rather the automatic molecular happenstance of polymerized organic molecules (DNA, RNA, and their associated products, enzymes, and the like) coming into contact with other molecules to form more complex life-forms (such as rudimentary cells). Symbiosis set the stage for all that came later, colonial cells, tissues, organs, and multicellular organisms.
All molecular and genetic evidence points to a counterintuitive conclusion: It was not some primitive prokaryote that exhibited particular favorable variations and evolved into a eukaryotic organism. Rather it was a series of favorable symbiotic events that allowed a large virus to infect some sort of primitive alga and give rise to a lineage of organisms that forever contained a membrane-bound nucleus.
Billions of years and countless infections later, these viral organisms are an integral, endogenous part of our own species’ genome. What are they doing there? The same thing viruses have done since the earliest stages of Earth history: inserting themselves into other organisms’ chromosomes and using the cellular replicative machinery of host organs to make more copies of themselves.
The astonishingly high viral component of the human genome75 reminds us that the genetic variation we all carry is due not only to the inheritance from human-like ancestors living on the savannah in the geologically recent past, but also from parasitism and modification by viruses, in symbiotic unions with more ancient roots.
As alluring as it may seem, the traditional Darwinian concept of “survival of the fittest”76 does not hold up in the light of what we know about endosymbiotic theory. Since viruses have been around since the Precambrian, constantly looking for new cellular hosts to infect, it should come as no surprise that they can jump from one species to another (as in the case of HIV, avian flu, swine flu, SARS, and the like). When they make the successful jump—a kind of intrepid exploitation of a new environmental niche—they go on to modify the genome of the species they infect. In this respect they are not the kind of gene transmission we have been taught to think of as “adaptive.” In other words it’s not always the “more fit” genome that gets passed on to the next generation. It’s also the lucky ones that happen to engage in a beneficial symbiotic union. “Fitness,” the ability to find a mate and leave many descendants, plays less of a role, and good fortune, and the ability to coexist with other living things, plays the bigger role in this view of evolution.
This means that the traditional Darwinian understanding of evolution—as individuals locked in a vicious “struggle for existence” in their adaptive quest to meet the demands of their environment—is not adequate. An individual is simultaneously coping with the circumstances of its own existence—the genes it inherited from parents, the bacterial load it carries on itself and inside its digestive, alimentary, reproductive, and excretory canals, and the viral load that is living and operating within its cells. All these factors together offer variables, in addition to the variables of the external environment, that affect the health and well-being of each individual in a population. The abiotic environment is perhaps the least important of these. The symbiotic environment may be the most.
Furthermore, natural selection functions not simply with respect to the heritable DNA of the species’ own gametes, but rather on a more inclusive set of genes from multiple organisms: the “host,” the bacterial flora in the gut, and the viruses inserted into the host’s genome. This tripartite collection is known as a holobiont, and since each component is dependent upon the others, evolution proceeds only with respect to the entire holobiontic organism. All eukaryotic organisms function in this interactive and symbiotic way, which means that adaptation is essentially a cooperative, rather than a selfish, enterprise.
Richard Dawkins popularized the idea of the “selfish” gene, expanding on the work of evolutionary theorist William Hamilton, as a way to envision how altruistic individuals evolve. Individuals come and go. They can be thought of as mere vessels that carry the real stuff of evolution, the genes that are passed on to offspring. The Dawkins worldview sees the genetic instructions that we carry as directives to do things that are in the genes’ best interest. Sometimes altruistic behavior isn’t in the best interest of the individual displaying it. Think of running into a burning house to save your three children. That act, which almost any parent would do at a moment’s notice, might result in an early death for the rescuer, but if it saved the kids, it would be worth it. From the selfish gene’s perspective, even if the rescuer died in the act, as long as the kids survived, three copies of 50 percent of the rescuer’s genes would live on. In any group of closely related individuals, self-sacrifice might actually promote the success of a large number of relatives who also share the altruist’s genes. Hence the gene benefits selfishly to make sure more copies of it are replicated, regardless of the health and well-being of the person carrying it.
Although it is often used to understand altruism—and is still very controversial at that—the “selfish gene” concept fails to explain the symbiotic tendencies of most life-forms. While we can see that viruses as well as bacteria may have initial stages of “plague culling” (high mortality rates during early phases of contact with new hosts), this is soon followed by coevolution of microbe and its host.77 Instead of replicators acting selfishly, it seems there is a stronger tendency for organisms to evolve together.
All this information leads us to one thought: that humans are more than just the sum of their DNA and their own adaptive “design.” Instead each of us is a holobiontic union of genetic material from mammalian ancestors, bacterial “machines,” and viral infections. All these genetic components work in concert to make us who we are. In one sense the union we form is a mingling of organisms that came together by happenstance. But it is crucial to understand that the holobiont is subject to natural selection, and that the different genetic systems have been fine-tuned over the course of evolution.
Perhaps the best illustration of this is where we started off this chapter, the endogenous retroviruses and their relatives that make up nearly half of the human genome. If this genetic material were simply “baggage” or “junk” DNA, we could liken it to a viral load on a PC, but this analogy is not sound. Everyone who uses Windows PCs remembers not so long ago, before virus-blocking software became standard equipment on new computers, that every time a computer made contact with the Internet it became the target of small indiscriminate programs that corrupted the boot-up process or the launching of a favorite program. These “computer viruses” are aptly named because they insert themselves into the informational stream of a program and corrupt its normal functioning. Computer viruses never led to any kind of evolutionary innovation in the workings of the computer programs, and this is because they don’t participate in the creation of new computer programs. They are released by unscrupulous hackers only after new programs are launched as the new “generation” of products hits the market. In this respect computer viruses are a decent analogy—in the sense that they insert themselves and co-opt the hardware of the machine by interfering with the host’s software—but since they don’t have any way of getting passed to new generations, they cannot be thought of as symbiotic.
We have a symbiotic relationship with viruses; we can’t live without them, even if we wanted to. This is a hard message to sell to a germ-obsessed public, but it’s the simple truth and it explains how our genome came to be riddled with so many viruses or viral components.78 Our relationship with viruses is complex; a recent discovery demonstrates that certain enzymes, found originally in viruses but lacking in bacteria, are active in determining the developmental path of human and indeed all animal embryos.79 Without this enzyme (reverse transcriptase), embryos fail to develop beyond the first few stages of life. Interestingly, reverse transcriptase was also found to be abundant in cancer tumors. Indeed this discovery helped point the way to a vital function for a large portion of the human genome whose function was previously unknown. Somewhere within this mass of genetic information that came from our viral symbionts lie the switches and signals that control the timing of cell division, and specify the shape and function of developing cells.
It’s not surprising that reverse transcriptase is most active in embryos and tumors. Both are comprised of cells that replicate prolifically, at undifferentiated stages in their life cycle. The chemical tendency of viruses has always been rapid and prolific replication, all the way back to a time when life was simpler, before the advent of eukaryotic cells, deep in the Precambrian past. The almost miraculous formation of an embryo and the grotesque and formless mass of tissue called a tumor are two sides of the same coin. In both instances reverse transcriptase is at work, dispassionately guiding the proliferation of eukaryotic cells80 to one end or the other.
The viral genomes that exist within us began as infecting agents and long ago killed off those individuals who were most susceptible to their pathological effects. After endogenization, they accumulated in the nuclear DNA of our ancestors. We share an important tradition with all plant and animal species: Viruses have acted like freeloading copilots inside us, hitchhiking and partially directing the ride through evolutionary time.