Ancient viruses in our DNA that might cause disease – wait, what?

I love when my friends or family come to me to talk about science! I got an email from my awesome friend Sarah Martin who wrote:

I want my favorite biochemist to tell me about how a virus can incorporate itself permanently into the human genome and I want to know more about the school of thought that evolution is driven by infection…

The news item she sent me reports: Ancient Virus May Cause Crippling Disease ALS, Study Finds. The study introduces a possible link between a devastating disease and a human endogenous retrovirus, which is not your average virus. It also mentions the role of human endogenous retroviruses in evolution. These are pretty complex ideas for one little news article, so let’s talk about the details and I’ll try not to ramble…

Research implicating an “ancient virus”

Let’s discuss this study first. ALS (Amyotrophic lateral sclerosis) is an incurable neurogenerative disease where motor neurons gradually die, causing a person to lose most of the important functions of their body within a few years. The cause in most cases is completely unknown.

There are many research groups out there studying ALS, viruses, and everything in between. Certain clues inspired this particular group at the National Institute for Neurological Disorders and Stroke to look for retroviruses in ALS patients. These clues included a discovery of “retrovirus activity” in the blood of some ALS patients, and the fact that some HIV patients suffer from nerve degeneration similar to ALS.

In their research, they found that some patients with ALS had elevated levels of a retrovirus called HERV-K. This virus was found specifically in the cortical and spinal neurons in some of the ALS patients, while none was found in the healthy control individuals tested.

20160328_153534

“Look at this study! What if…”

Like most studies, this research does not yet explain the cause of ALS but does help direct further research into how ALS might be tackled. This finding is interesting for those affected with ALS because it provides a potential target for therapy. If a virus causes the disease, then drug development efforts can focus on stopping the virus.

A really interesting thing about this retrovirus is that it lives in our DNA – we are born with it. It’s something called a “human endogenous retrovirus”, or HERV – and it became part of our DNA between 2-5 MILLION years ago. Let’s talk about THAT!

Ancient virus baggage                                                            

First things first: what is a virus? A virus is basically a package of genetic material that has evolved a way to replicate itself. They aren’t considered living organisms, like other small pathogens such as bacteria, and they really are quite simple in their build (and elegant, if you ask me). How they work isn’t as simple though, and there are different types of viruses. Some have DNA, but some have RNA instead; some work by inserting themselves into your DNA (retroviruses like HIV), and some work by just using your proteins and leaving your DNA alone. The one thing they all have in common, though, is they need to take over the machinery in your cells to replicate.

A retrovirus like HIV works by inserting itself into your DNA. Crazy, right? That’s why it’s so hard to cure! In this case, it is immune cells, or white blood cells, where the HIV takes residence. It’s safe from detection in there, and its genes are read in the same way your own genes are read by the cell’s machinery.

herv virus 1

[overly simplified visual]

What’s the difference between a retrovirus like HIV, and this “endogenous retrovirus” called HERV-K? Well, the main difference is that a person gets HIV from outside their body; but we are born with these endogenous retroviruses.

An endogenous retrovirus used to be a virus like HIV that, at one point, infected a human and inserted its DNA into our ancestors’ cells. But not just any cells – in this case, it was inserted in cells of the germ line. What do I mean germ line? We have DNA (coding our genes) in every cell in our body. But the DNA that gets passed down to our kids is specifically the stuff in eggs and sperm. So, say I catch a retrovirus – it could insert itself into the DNA in some of my cells, but it can only be passed on to future generations if it inserts into the cells specifically located inside my ovaries. A virus like HIV doesn’t do that because it has an affinity for immune cells, (which is why it causes immunodeficiency).

Even though these special circumstances are required, integration of retroviruses into the germ line has happened often enough throughout our evolutionary history that 1% of our entire genome is made up of these “virus fossils”.

Research into endogenous retroviruses is revealing that they may play potential roles in some diseases. Aside from ALS, evidence has implicated their involvement in cancer and certain autoimmune diseases as well.

On the other hand, because they have been part of our DNA (and other animal’s DNA) for MILLIONS of years, their presence has undoubtedly had a number of effects, negative OR positive – one of them being our own evolution.

How could a virus fossil play a role in evolution? 

Evolution is the changing of a population of organisms to adapt to its environment. This adaptation comes about from variation within our genes – often times, spontaneous mutations that happen to allow one organism to be better off than another of its population. Because that one is better suited to the environment, it tends to survive and reproduce more, and thus its genes tend to get passed on more often.

Random mutations are usually one-letter changes in our DNA code. Often these changes don’t make a difference, or they could have a slightly negative effect, or they could have a slightly positive effect, depending on where it happens within a gene. Now think about a retrovirus – this would be a whole string of DNA (a set of virus genes) inserted directly into your set of genes. Obviously this sounds like it would be bad – but could it be good? It would have to for it to play a role in our evolution, right?20160328_165334

For this newly inserted DNA chunk to be a “bad” thing for an organism, it would have to cause early death or prevent reproduction. Otherwise, it would be passed along.  As it gets passed along, mutations occur that prevent the virus from actually working like a virus anymore – which is a good thing for the organism.

Let’s consider an example: evolution of the placenta. A current super-interesting model states that a retrovirus at some point in our past actually helped in the evolution of mammals about 150 million years ago. The placenta allows a developing fetus to gain nutrients from the mother by attaching to the wall of the uterus, and it does this by creating a layer of fused cells. It also protects the developing fetus, with its proteins from both mother and “foreign” ones from the father, from immune attack. Cell fusion and immune suppression are attributes common to viruses. Research into placental development in recent decades uncovered virus-like particles at the placenta interface in monkeys, and then potential endogenous retrovirus sequences, and finally the discovery of the protein, syncytin, which came from a gene within an endogenous retrovirus sequence. Subsequent studies of this protein in mice showed its vital role in embryonic development – when they deleted it from mice, the placenta did not form properly and the embryos died.

How do we know that it played a role in evolution?  Mammals share similar traits, like placental development, because we evolved from common ancestors and share common genes. Our genes have become slightly different over time from genes of other mammals, but they are still similar enough to recognize as the same. And, we find similar syncytin sequences in primates and other mammals.

DNA sequences have more information than just who you are… they can tell us who we were, and how living things – and non-living things like viruses – are all connected.

Conclusions

The research goes on!

 

Featured image: Flickr, B0009743 DNA double helix, illustration; Credit: Maurizio De Angelis, Wellcome Images

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