Have you ever had a cold that you just couldn’t shake? One that seemed to take months to release its vicious grip on your abused body? Definitely NOT fun. Now imagine an infection that hangs on for millions of years. Yep, we’ve all got it, and what’s worse, when we became infected, it wasn’t just with the common cold either. We came down with things like ebola and many, many other horrors, and we still have them. Why aren’t we dead yet? Read on.
I’ve been writing a series about the twisting tale of evolutionary genetic engineering that has effectively glued us together from parts that are as disparate as Neanderthals (my first post of the series, “Cavemen in Your Genes”) and bacteria (“Evolution’s Usual Suspects: 1. Plagiarizing Wizards”). This is the next installation of that series, continuing the theme of primordial “crimes” that birthed the chimaera that we call human. Last time, I rambled about how bacteria plagiarize each other’s DNA by the process of horizontal gene transfer. Like a child building a Lego structure, they can snap foreign DNA into their own chromosome. This process speeds up evolution by allowing beneficial mutations to spread across a much larger community with lightning speed. Today’s crime sets our body’s defenses bristling: hijacking.
Although we humans possess a few genes that bacteria have spliced into our chromosomes (yes, you are part bacterium! How does that make you feel?), only a very small part of our genetic heritage appears to be bacterial. Big deal, right? Sure, it’s an interesting process, but so what if it makes only a small splash in our history?
Well, it turns out that another group of even stranger “life” forms is responsible for about 8% of our genome — over 98,000 sections of DNA. That’s a big splash in our gene pool. I have placed the word “life” into quotation marks because these entities push the definition of life to its limits. These creatures are very, very tiny, much smaller than bacteria. They are viruses, specifically a group of viruses called endogenous retroviruses (ERVs).
What does this mean? Let’s back up a bit and build it up from its parts.
Recall that a virus is really just a protective shell of protein housing a relatively short string of genes that consists of the instructions for making more protein coat and genes. That’s basically it. How does it “live”, being so simple? It hijacks the cellular machinery of other DNA-based life forms, and it absolutely requires such a host for any sort of activity at all. Viruses are the very distilled essence of a parasite. Parasitism is ALL they do. This is why their identity as living things is questionable: are viruses really alive when floating completely inertly between the animals, plants and bacteria that they infect?
When viruses encounter a cell, they enter it in various ways, depending on the type of virus. I think that bacteriophage viruses are the most marvelous by far: they look like Apollo moon landers and they inject their DNA into bacteria using what amounts to a molecular syringe.
Once inside the cell, the viral DNA subverts the cell’s own protein factories (ribosomes), and gets to work. Such work, in the case case of viruses, is to make more viruses. Lots more. So much, in fact, that they eventually accumulate to the point that they burst the cell open — much like the chest-burster alien in Ridley Scott’s classic film. And just as the Hollywood alien made a rather nasty mess of its victims, viruses can similarly reduce their unfortunate host’s cells (and sometimes the entire host) to a bloody mess. The most infamous example is ebola, a particularly virulent hemorrhagic virus from Africa that causes blood vessels to disintegrate, leading to an agonizing bleeding death.
But hang on…isn’t the common cold also a virus? Yes, and it doesn’t generally dissolve its victims. Most viruses are not as aggressive and globally destructive as ebola or the Marburg virus. Most of them might cause local damage by destroying some cells, but they reign in their ferocity before they kill their victims. Why?
Evolution of Avirulence: It Pays Off to be Nice
Comparatively benign viruses are one stable result of natural selection, and they demonstrate evolution especially well. The process by which they arise from vicious viruses is called the evolution of avirulence. This means that viruses are selected by their host’s survival patterns to become less virulent or lethal. It’s simple logic:
Suppose Virus A is a ferocious killing machine, slaughtering its hosts with ebola-like efficiency within a few days (= highly virulent), whereas Virus B is like the common cold, causing a few annoying symptoms as it destroys some cells, but not very aggressive, and leaving its host alive (= relatively avirulent). Which type will survive and spread better?
Although Virus A will produce a lot more copies of itself in any one host (hijacking nearly all of the host’s cells to produce more Virus A), it handicaps its own spread through the population of hosts. Why? It’s because hosts die so quickly that they have little chance of shaking hands with other hosts and spreading the virus. Also, other hosts may learn to keep their distance from an infected individual that is rapidly dissolving into a nasty mess. So Virus A has a serious chance of going extinct.
Virus B, on the other hand, produces relatively few copies of itself in a single host, but the resulting symptoms are so benign that the host might not even realize that it’s infected before it shakes hands with, kisses, or wrestles with others. The virus therefore has a great chance of spreading to other hosts, securing its survival. Over the whole population of hosts then, Virus B actually produces more copies of itself than Virus A. So Virus B is a better competitor than Virus A, and over time B will likely replace A in the population.
But random mutations sometimes cause individuals of Virus A to lose some of their efficiency (by damaging their genetic code), thus reducing their aggression…and making them more like Virus B. Because this mutated population will survive better than the original fierce one (we showed this above), it will ultimately replace the original population. Over time, the descendants of the originally nasty Virus A evolve into relatively more benign forms very much like Virus B. This is the evolution of avirulence by natural selection. It pays off to refrain from ruining your landlord.
Bunny Boom’s Bust Blunted
Neat idea, but do we ever actually see this happen? Yes. One well-know example involves the myxoma virus in rabbits . Rabbits are a severe pest in Australia because they were introduced by humans to an ecosystem where they lacked natural enemies. As a result, they multiplied like…well, bunnies. Their skyrocketing populations devastated the local plant life and crops. Among the methods of population control applied to them was the the disease myxomatosis, transmitted by the nasty tumor-causing myxoma virus.
The myxoma virus was found in Uruguay, where it only affected rabbits in a relatively mild way. However, when it was accidentally released in Europe, it quickly obliterated 90% to over 99% of rabbits in some populations (which lacked the immune defenses of rabbits from Uruguay), killing within 14 days. So the virus was deliberately released in Australia in the 1950s to curtail the rabbit population there. It was initially very successful, killing nearly 90% of rabbits within two years. Over time, however, the virulent form of the virus was replaced by avirulent forms, which now have a mortality rate of only about 50% — still high, but only about half of the original potency.
Actually, the evolution of avirulence is a combination of natural selection on both the host and the virus, because a virulent virus represents an extraordinarily strong force of selection on the host, whittling down a lot of the host population that does not possess especially strong immune defenses. In the end, the parties meet somewhere in between: the virus loses some of its aggression and destructiveness, and the host evolves strengthened immune defenses. The rabbit-myxoma case is thus a textbook example of what is referred to by evolutionary biologists as coevolution, meaning that two life forms influence each other’s direction and rate of evolution. Indeed, if you are interested in reading about the documentation of evolution in action, the case of rabbits versus myxoma virus is not a bad place to start.
Retroviruses: Not from the ’80s
OK, so viruses can evolve to lose some of their punch, and can coexist with host populations without ravaging them. But how on earth did they manage to sneak into our genome? If they hijack cells and then merely dispense of the remains, then how can their genetic material be passed on to our children? To answer this, we turn to a very special group of viruses called retroviruses.
Retroviruses have a neat trick. They can “upload” their genetic material to the chromosomes of their hosts, which allows them to piggyback on their host’s DNA, simplifying their job of replication and avoiding detection by the host. Stealthy.
No, retroviruses are not from the ’80s. Rather, their name refers to the “backward” way in which they transfer the information that resides on their genetic blueprints. (By the way, Retro fans, I’m not calling you backward; “retro” merely means “in reverse”.) Retroviruses are the only known life forms to store genetic material in the form of RNA (ribonucleic acid) instead of DNA (deoxyribonucleic acid). RNA normally functions like a work order, the chemically “active” form of the instructions encoded in DNA, making these instructions ready for translation into proteins. But retroviruses use RNA for information storage as well. Retroviruses make use of the host’s own means of copying genetic material into RNA to make more of themselves. To do this, they must make a DNA copy of themselves (using a special copying enzyme, called “reverse transcriptase”) and insert this DNA into the host’s genome. The “retro” in their name comes from this backward order of the usual direction of copying: RNA copied to DNA.
So retroviruses have a kind of dual identity: when they are floating between hosts, their genetic material consists of RNA, but when they have infected a host, they are really just a section of DNA in the host’s genome, in a form known as a “provirus”. It is in the provirus state that they became part of our genetic heritage, for once among our genes, they can be passed on to our children if they infect sperm or egg cells (or the progenitors of sperm and eggs). Infecting egg cells is a great way for a retrovirus to get free population growth without expending any energy if the egg cell becomes fertilized: because the provirus gets copied each time the host cell divides, its numbers can swell from one provirus copy to several trillion as the fertilized egg cell divides repeatedly and the host grows into a mature individual.
You can imagine how difficult it is to detect retrovirus infection and to treat it, once the provirus hides among our own genes. Retroviruses are some of the sneakiest pathogens and therefore cause some nasty and persistent diseases. AIDS, caused by the human immunodefficiency virus (HIV) is probably the best known, but a viral nature is also suspected for several autoimmune diseases such as multiple sclerosis . Retroviruses can linger in our genes in a dormant provirus state for long periods until a suitable trigger comes along; perhaps stress of some kind. The factors that induce activity of the virus are not always well understood.
Sometimes, these proviral retroviruses never even wake from their DNA slumber. A suitable mutation may make them unable to become activated, and in such cases they become endogenous retroviruses, or ERVs, which become incorporated permanently in our DNA. Many of them then fall into the huge pool of “junk” DNA that separates our useful genes on our chromosomes. We can still recognize them as being related to exogenous (not permanently implanted) retroviruses when we analyze their DNA sequences. In fact, a recent study of the human genome has yielded the amazing result that not only is about 8% of our genome composed of ERVs, but that many of their gene sequences are disturbingly closely related to ebola, marburg virus and bornavirus .
Luckily, virulent though their ancestors were, most ERVs in our genome are effectively like a fly splattered on a wall at this point — most of them, that is. There are a few exciting exceptions, which paint a really neat picture of evolution leading to a sort of “rehabilitation of a felon”.
Hijackers in Rehab: Beneficial ERVs
Having become stuck in the genomes of organisms as diverse as bacteria and primates, some ERVs do not idle along as inert junk DNA but have evolved with their host to actively benefit the composite creature that forms from their union. It’s reminiscent of the premise of the 1958 movie “The Defiant Ones“, in which two escaped convicts, linked by a chain, learn to cooperate to evade capture, even though they do not get along well at first.
The Liverpool Endemic Strain of a common infectious bacterium found in hospitals worldwide is the most virulent form of the species Pseudomonas aeruginosa. Recently, a team of scientists led by Dr. Craig Winstanley of the University of Liverpool found that this virulent strain differed from less aggressive strains of the bacterium by about 10% of its genome . Most interestingly, much of the DNA constituting this 10% difference was made up of prophages — the bacterial equivalent of provirus ERVs. Somehow, the viral genes made this bacterium more competitive than its conspecifics (others of the same species). This is a wonderful example of how evolution can proceed via not just mutation but by the fusing of two organisms. Thus, this is one mechanism by which we see an increase in complexity. It’s a little like the genetic fusion that Jeff Goldblum’s character experiences in the 1986 remake of “The Fly“.
A second example of beneficial ERVs hits closer to home. Amazingly, an ancient ERV similar to HIV may be responsible for promoting the prevention of cancer in primates . Comparison of gene sequences of several primate species suggests that they were infected by a HIV-like retrovirus around 40 million years ago. This retrovirus became incorporated as an ERV, but it also then appears to have transformed into what is called a transposable element, popularly called a “jumping gene”. Transposable elements do just that — they make copies of themselves and reinsert their copies in multiple places in the genome, much like an ERV is expected to behave, and they appear to have descended from ERVs. The importance in the present case is that a DNA-repairing protein produced by primate cells, called p53, bound particularly well to the ERV (many proteins bind or stick to DNA for various reasons, including stabilizing them), and therefore was able to act on a much larger number of genes after the ERV spread itself around the genome. As a result, its protective capacity increased enormously, and is today sometimes referred to as “the guardian of the genome”. DNA repair, as you may know, is important in cancer prevention, because many cancers result from errors in copying DNA or from damaged DNA. Therefore, an initially viral infection 40 million years ago may have turned beneficial and ultimately facilitated an increased competitiveness of primates.
Finally, if you’re an expectant mother, have you ever stopped to wonder why your body does not reject your child the way it would respond to an infection? After all, the genetic contribution from dad makes the child genetically different from you, and the fetus should be perceived by the body as foreign tissue, much as a transplanted organ. But there is obviously no immune response (fortunately!), so what’s going on? It turns out that some very ancient ERVs have evolved to fill the role of a kind of immune system regulator that prevents the body from attacking the baby and placenta, in a process called gestational immune tolerance [6, 7]. This makes sense if you think about it, for viruses are experts at circumventing the body’s immune system. Therefore, an immunosuppressant role of a fully integrated ERV is a natural extension of its ancient viral activity. In fact, the presence and activation of ERVs during pregnancy in nearly all mammals, such as sheep , has led to the hypothesis that the ERVs were partly responsible for the evolution of viviparity (gestation of an embryo within a mother’s body) from oviparity (egg-laying).
The role of endogenous retroviruses in host functions is very strong evidence for coevolution of host and parasite. Arguments of creationists against the idea hinge on (1) the assumption that mutations can only lead to degeneration of health (which is demonstrably untrue; see short discussion in my last blog entry) and (2) the inexplicability of an infectious origin for ERVs that have a fixed chromosomal position (i.e. ERVs that do not move around in the chromosome like jumping genes). It simply seems unlikely to creationists that this could have occurred based on the cosmopolitan distribution of such ERVs across so many species. By contrast, the most parsimonious (simplest) explanation, which does not require the intervention of an intelligent agent (and which is supported elegantly by observation), is that such ERV infection occurred in organisms extremely long ago, and that the resulting ERVs were passed down to all of the descendants of these species, in all of the lineages of life that branched out from such common ancestors. Of course it’s possible that all of life, the universe and everything were created only 6000 years ago and were made to look exactly as though they were 13.7 billion years old, but this explanation requires many more assumptions to support it. The entire purpose of science is to seek out the most parsimonious explanation for a set of observations, because experience repeatedly shows that the most parsimonious explanation tends to be the right one.
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