Sunday, September 11, 2011
How did that pesky virus end up in our DNA?
Last time we talked about the different types of genetic and epigenetic chimeras. We learned what a chimeric virus is, and that retroviruses need to get integrated into the host's DNA in order to replicate. They basically inject their RNA into the cell, the RNA gets transformed into DNA, the viral DNA enters the cell's nucleus and once in the the nucleus it's integrated into the cell's DNA.
This process has been going on for as long as viruses have existed. And viruses have existed for a long time.
Normally we think of viruses as pesky little things. Flu viruses are annoying, more serious viruses like HIV or HCV are deadly. Well, you'll be surprised to know that over the course of evolution, viruses have driven genetic diversity by transferring genes across species. How do we know that? We know because we all carry ancestral DNA derived from viruses in our genome. There are roughly 100,000 copies of endogenous retroviral DNA in our genome . In other words, we're all chimeras!
But... how did the retroviral DNA get there?
The mechanism is fascinating. You see, when a virus enters the body, it has one purpose: replicate, and to do so it needs to infect cells. Every virus has its own preferential cells. HIV, for example, infects mostly T-lymphocytes, but it also creates huge reservoirs in the guts. So imagine a platoon of viral particles trying to eat up whatever they can as they migrate around the body. Well, sooner or later, some virus will find a very special set of cells: the gametocytes, a.k.a. oocytes in women, and spermatocytes in men. And once in there the virus is stuck. Because you see, gametocytes will not duplicate unless they get fertilized. But by then the virus is no longer active. It's literally stuck, in the sense that the integrated viral DNA now cannot replicate and cannot escape the host's DNA.
What happens if the infected gametocyte gets fertilized?
Once fertilized, the cells start reproducing very fast. Every cell in the newly created embryo will carry the bit of viral DNA, which has now become non-coding. The new individual will carry the viral proteins everywhere, even in his/her own gametocytes, and hence the viral proteins will be inherited by his/her offsprings as well.
And that's how viruses ended up in our genome a long, long time ago.
Wait, my story isn't over yet. Now I'd like to convince you that this hasn't been some futile genetic exercise. Remember, I'm a fan of non-coding DNA. It holds the key to evolution. And as species continued to evolve, sure enough, Mother Nature found a way to use those non-coding viral proteins. The viral genes became beneficial to the host.
Here's the scoop: viral genes are expressed in the placenta . Why? Well, we don't know for sure, but the hypothesis are intriguing .
Retroviruses debilitate the immune system. In general, this is not a good thing for the body, except in one very special instance: an embryo is literally a parasite growing inside the mother's body. It carries extraneous DNA and, under normal circumstances, something carrying extraneous DNA would be considered by the immune system an antigen. But a fetus is not to be considered an antigen. Therefore, the expressed viral proteins found in the trophoblasts, the outer layer of the placenta, would have the role of suppressing a possible immune reaction against fetal blood.
Another property viruses have is that of cell fusion: they literally "merge" cells together into one membrane. A second hypothesis is that this property is used during the development of the placenta to build a barrier between the maternal circulation and the fetal circulation.
Let me conclude with a caveat: as always, when talking about evolution, it's easy to slip into thinking that certain genes evolved to fulfill a specific function. In reality, we know the placenta evolved because it presented an advantage compared to laying eggs. The beauty of DNA is that it holds not just the present information, but the memory of the information needed to get there. It's this redundancy that allows it to explore new solutions, but it's only a posteriori that we can retrace this path and give it a meaning.
 Emerman M, & Malik HS (2010). Paleovirology--modern consequences of ancient viruses. PLoS biology, 8 (2) PMID: 20161719
 Dunlap KA, Palmarini M, Varela M, Burghardt RC, Hayashi K, Farmer JL, & Spencer TE (2006). Endogenous retroviruses regulate periimplantation placental growth and differentiation. Proceedings of the National Academy of Sciences of the United States of America, 103 (39), 14390-5 PMID: 16980413
 Dupressoir A, & Heidmann T (2011). [Syncytins - retroviral envelope genes captured for the benefit of placental development]. Medecine sciences : M/S, 27 (2), 163-9 PMID: 21382324
Picture: Onion blossom. Canon 40D, shutter speed 1/500, focal length 85mm. The deer repellent spray may have something to do with the weird horn-like growth. It's been three months and the thing hasn't blossomed yet. I think next time I'll let nature take its course.