divulgatum está dedicado a la difusión de conocimiento científico en español e inglés, mediante artículos que tratan en detalle toda clase de temas fascinantes pero poco conocidos.
divulgatum is devoted to the dissemination of scientific knowledge in Spanish and English, through articles that go into the details of all sorts of fascinating, if not
widely known, subjects.

Wednesday, December 23, 2015

An eternal battleground

One of nature’s primordial conflicts could turn out to be the propelling force behind evolution.

The physical structure of the particles of some bacteriophage viruses are the perfect example of the sophistication exhibited by these organisms. (Image adaptaded from original by Michael Wurtz.)

LIKE IT or not, war is the most powerful driving force of material progress on our planet. This is attested by such indispensable inventions as radar, the computer or the reaction engine, which were born in the most horrendous of conflicts, the Second World War. It is a typical error of an anthropocentric mentality, however, to think that war, together with the rapid development that it sparks, is something intrinsically human. Aggressive competition between living beings not only stretches back to the origins of life on Earth but, in a similar way, it may be the underlying cause of the imposing variety and complexity of life that we see all around us. And among all the conflicts that have propelled the evolution of life, the most important, prolonged and vicious one is that which brings viral organisms (viruses) and cellular organisms (composed of one or more cells) face to face. This war has been raging, silently but tirelessly, each second of the last three billion years, and is still raging in this precise instant, in the ground we step on, in the objects we use, in the food we eat, and in ourselves. A healthy human body, with its ten trillion cells, is the home of ten times as many microorganisms, such as bacteria, and a hundred times as many viral particles, or virions (those minuscule agents that we mistakenly know as ‘viruses’). Many of these ‘companions’ not only have no negative effect on our health, but are necessary to maintain it. This does not downplay the fact that, within each of us, the most ancient war on this world continues on its course: a struggle for survival and domination, based on the constant invention, upgrade and stealing of molecular weapons, which is a reflection of the ruthless and marvellous nature of life.

On the other hand, it is true that all the cellular life forms — animals, plants, fungi, bacteria, protozoa, chromists and archaea, in all their variants — compete tenaciously against each other. What, then, makes the war between viruses and cells so unique and essential for life? The answer arises from a controversial series of discoveries that place the origin of viruses in an extraordinarily ancient world, preceding multicellular life and inhabited by much more primitive microorganisms than those around us today. The antagonism between viruses and cells has thus existed since the dawn of evolution, and so its impact on it may have been greater than that of any other factor.

Viruses are undoubtedly the most mysterious biological entities on this planet; virtually any aspect of them, from their definition as living creatures or as simple organic particles, to their origin or their role in the biosphere, is witness to a clash of radically opposing views and theories. Defining the nature of a virus implies no less than defining the line that divides what we consider ‘life’ and what we do not. Throughout the twentieth century, the detailed study of viral particles led to a universal image of viruses as mere ensembles of proteins and nucleic acids that, sheltered by natural selection, escaped from the cell and managed to exploit its machinery in order to replicate themselves; a displeasing by-product of evolution. Manifold biologists today still describe viruses as ‘genetic pickpockets’ that arise and evolve by means of the systematic theft of cellular genes. The significance of the impact of viruses on the evolution of life has also been astonishingly undervalued.

The drastic turning point in science’s perception of viruses came in 2002, with the discovery of the so-called giant viruses. During the study of microorganisms infecting certain amoeba species, French researchers found something that, according to its size, seemed to be a bacterium. Nevertheless, it was soon clear that this microbe was genetically and physically different from any cellular organism. It was a virus of unprecedented dimensions, capable of exceeding many bacteria in both physical and genomic size. This first giant virus, baptised mimivirus, was followed all too soon by other species, such as the marseillevirus and the pandoravirus. The definition of viruses, originally stemming from their ‘invisible’ character under the microscope, was crying out to be reconsidered. Some of the researchers responsible for the discovery proposed a new classifying system for living organisms, which divided them into two major groups: cellular organisms and viral organisms.
 As the main proof that viruses are legitimate life forms, they pointed to what happens during the infectious stage of a virus’ life cycle. Once the viral particles (virions) have managed to invade a cell, an extraordinary phenomenon takes place: a new structure — visible on the microscope — emerges in the infected cell, which contains and protects the virus’ genetic material (genome). While this structure, called the viral factory, manufactures thousands of new virions, charged with copies of the invading genome, the virus’ offensive systems degrade the cell’s own genome. The result is a cell without a functional genome — that is, without life — wherein the viral genome is rapidly expressed and multiplied, by making use of the sophisticated machinery of the murdered cell. Therefore, the organism that we see under the microscope at this stage is by no means a cell with thousands of tiny ‘viruses’ in it; it is no less than a virus in its living form, employing the cellular sheath and machinery of its victim to produce an army of virions, with the aim of spreading itself to other cells. The virions, those lifeless particles considered as the definitive form of the virus for more than a hundred years, actually reveal themselves as simple ‘seeds’ or ‘spores’ used by the virus for dispersing its genes. For more than a century, by mistaking the virus for its virion, science has committed a terrible error, comparable to mistaking a tree for a seed, or a human being for a spermatozoon. A virion is just as inert as a seed, incapable of growing and reproducing until it is placed in the appropriate environment. The difference lies in the fact that, similarly to other intracellular parasites — such as bacteria of the Rickettsia genus — a virus needs to invade a cell and make use of its resources to live. In this sense, viruses are, in fact, cellular organisms, since during their metabolically active phase they always have a cell, even if it is a ‘borrowed’ cell. This reflects the extreme intelligence and elegance that underlie the minimalist design of viruses — the fruit of an inconceivably prolonged evolutionary process. 

Mimivirus' viral factory (centre) and virions in different stages of development (hexagons) around it, inside an infected amoeba. (Credit: Didier Raoult.)

Even so, many biologists continue to reject the concept of viruses as living creatures. The mimivirus, however, still had something to contribute in this regard: its own proof of life. While studying the giant virus, the researchers found particles of a second, much smaller virus, around the first. When this tiny satellite virus, nicknamed sputnik, was present together with the giant mimivirus inside an infected amoeba, the biologists confirmed that the mimivirus had trouble reproducing, thus allowing the amoeba to survive the attack. Sputnik was the first known virophage, a virus that exclusively infects other viruses. The possibility that a virus could be infected by another had never been contemplated, and constitutes a capital proof that viruses are alive, insofar as only a living creature can be infected by a virus. That is, viruses have independently asserted themselves as living creatures!

What is, then, the true origin of viruses and their role in the evolution of life? In contrast to what numerous scientists believe, viruses are not ‘genetic pickpockets’ that survive by stealing cellular genes. Rather the opposite; most viral proteins have no equivalent in any cell known, indicating that the origin of viruses is extremely ancient, going back in time to a world inhabited not by today’s cells, but by more primitive ones that, over time, gave rise to those. A reasonable hypothesis is that viruses come from a group of primeval cells that gradually adapted to parasitic life; the structure and genome of these cells experienced enormous simplification as they developed a greater dependence on the genes and components of other cells. This phenomenon, termed reductive evolution, reached its pinnacle in viruses. Relying on a minute number of proteins, these organisms have been able to develop structures of an amazing complexity and ingenuity, specifically designed to dodge each one of their victims’ defences, and in which a single protein can play a multitude of roles. Billions of years of evolution have turned viruses into the best designed and adapted life forms on the planet; it is because of this that no organism — not even humans, not even viruses themselves — can definitively escape their attack.

The idea that viruses have had a fundamental impact on the evolution of life draws upon the observation that they are real cradles of genetic diversity; their ability to mutate in minimal time periods allows them to evolve new genes. Not only this, but it is actually cells, and not viruses, which are the ‘pickpockets’ gleaning a constant flow of new genes from viruses. A clear example of this are the viruses that infect bacteria (bacteriophages), which play a major role in the direct transfer of DNA between these organisms, promoting evolutionary processes that do not depend on the traditional gene flow from parents to offspring. As far as we humans are concerned, it might come as a surprise that around forty-two percent of human genetic material has a viral origin. Part of this material has undoubtedly had a pivotal role in the course of our evolution; as a matter of fact, one of the essential genes for the development of the placenta was concocted millions of years ago by a virus, before ending up ‘inserted’ in the genome of an ancestor of the first mammal. It is no less surprising that the major difference between our genome and that of the chimpanzee is precisely the number, variety and location of elements of viral origin that are part of the genetic material of both species. Some theories go as far as suggesting that the origin of DNA itself, as well as of its replication mechanisms, first emerged in viruses and was subsequently adopted by primitive cells, based until then on RNA, a simpler type of nucleic acid.

The true diversity of viral organisms is, beyond any doubt, huge, and it remains for the most part unexplored. It is evident, however, that the role of viruses in the history of life has been immensely more relevant than many still believe. Our ‘cellulocentric’ vision of the world has led us to overlook the effect of the eternal struggle between the virus and its host, which nevertheless contributes to channelling the marvellous process of evolution, from which every life form benefits. Therefore, the cellular and the viral worlds have evolved in parallel, but in essentially different ways; one, toward increasingly complex forms; the other, toward utter simplicity. This three-billion-year-old predation, with its inexhaustible and ever-changing repertoire of arms, tactics and deceptions, is probably responsible for every living creature, be it virus, bacterium, amoeba or human, as it is today. After all, nothing fits better with the inimitable nature of this world than the idea that the fascinating complexity of life may be the fruit of the creativity of the simplest of beings.

Special thanks are due to Isobelle Bolton for her invaluable help with translation.

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