Fossil Viruses in the Human Genome

There is a commonly-heard idea that Japanese science is not creative, although they are very good at refining other people’s ideas. This idea is commonly heard even in Japan; I’ve had to disabuse quite a few of my students of the idea. Including some of the ones working as research scientists. It is true that Japan has yet to produce a Newton, Darwin, or Einstein, but then there really haven’t been very many of them in history. Japan does produce high-quality original research, so I’m going to introduce a bit of it on my blog.

My standard is simple: I will introduce articles published in Nature, with an accompanying News and Views analysis, that were produced by researchers working in Japan, possibly in collaboration with other nations. Because I don’t have time to check every article’s origin, there is, at least for now, another practical requirement: the first author needs to have a Japanese-looking name, or the News and Views article needs to mention where the research was done. This would be bad if I was trying to be systematic, but I’m not.

The other two conditions are meaningful. Nature is the most influential science journal in the world, just about beating Science, the main competition. This means that any articles published in it are important research. The News and Views articles are written about a small proportion of the articles (normally called “letters”, for historical reasons), with the editors choosing the ones of most general interest and importance. Thus, getting an article in Nature, with a News and Views commentary, means that your research is of the highest normal global quality. Realistically, this is the best you can aim for.

I will link to the articles on the Nature site, but while the editorial summary can be read for free, the actual articles need a paid-for subscription. If you’re at a university, your university probably has one; otherwise, you need a personal subscription to Nature. If you’re interested in science, I think it’s well worth it, but it’s not cheap.

Obviously, these articles will be a bit irregular, depending on when appropriate papers appear in Nature.

Anyway, on to this time’s paper. The research was mainly done by a group at BIKEN, in Osaka, by Masayuki Horie and Tomoyuki Honda, with assistance from a lot of people (the author list is in the freely-accessible information).

It is well-known to biologists that a large proportion of the human genome (about 8%) comes from viruses. Bits of the viral genome get incorporated in chromosomes, and then reproduced with the rest of human DNA. All the previously known examples were from retroviruses. Retroviruses are so-called because they reproduce by first converting their RNA genome into DNA, and then using the machinery of the infected cell to make more RNA from the DNA template. Integration of this DNA into the host genome is relatively common, and may, actually, be a normal part of the process; as this article isn’t about retroviruses I’m working from memory.

This paper reports the discovery of DNA elements derived from Borna viruses, a different class. These viruses have RNA genomes, but do not normally integrate any DNA into the host genome. However, they do carry out their entire life cycle within the cell nucleus, the part that contains the host DNA. Further, they naturally infect neurons, cells that do not normally die, and so the infection can be extremely persistent.

The researchers started by searching the databases of genome sequences for sections that matched sequences from the Borna virus genome. They found plenty. There were several in humans, some of which appear to still function as genes; that is, the DNA could be transcribed to messenger RNA and then made into proteins, and in one case there is already evidence that it is. Most of the insertions, however, have lost bits over time, and can no longer be used to make proteins; these are called pseudogenes or fossil genes. By looking at the presence of similar sequences in related primates, the authors determine that the virus must have been integrated into the genome about 40 million years ago, because it is in all the primates that split off from the lineage that leads to humans after that time, but not in the ones that split off before that.

They also found evidence for the virus genes in other animals, with varying dates for integration.

For the viral genes to be inherited, they have to be incorporated in the germ line; that is, in the eggs and sperm that go on to make the next generation. Since the virus normally infects neurons, a different class of cells, this might be relatively rare, so the authors looked to see whether the viral genes get incorporated into the DNA of neurons. It turns out that they do, and that this seems to be quite frequent.

The incorporation of the DNA is blamed on so-called L1 elements, elements of DNA found in mammalian genomes that reproduce themselves throughout the genome. Their machinery seems prone to picking up a particular gene from Borna viruses, and incorporating it instead. (All of the insertions were derived from one of the Borna virus genes, a gene for the protein shell that encapsulates the virus when it leaves the cell.)

So, what’s the significance of this?

From a pure science perspective, it’s the first evidence for contributions from a virus other than a retrovirus to the human genome, which is interesting in itself.

The 40 million year age is also interesting, because so-called RNA clock methods for measuring the age of Borna viruses suggest that they are much younger than that. (An RNA clock works by measuring the rate of mutation in the genome, and then looking at changes, or at how long the virus could be stable.) This suggests that the RNA clock doesn’t work very well for viruses.

Finally, incorporating bits of DNA into the genome in random places can disrupt the cell’s function. It can cause cancer, but also have other effects. There is, apparently, some (disputed) evidence associating Borna-virus infection with mental illness, and this provides a mechanism by which the virus could have that effect. Disruptions to neural functioning could, of course, cause mental illness of various kinds.

Viral ‘fossils’ in the genome (Editor’s summary)

Virology: Bornavirus enters the genome (News and Views article: Nature 463, 39-40 (7 January 2010) | doi:10.1038/463039a; Published online 6 January 2010)

Endogenous non-retroviral RNA virus elements in mammalian genomes (Original paper: Nature 463, 84-87 (7 January 2010) | doi:10.1038/nature08695)

Posted in Science.

2 Comments

  1. Thank you for starting this interesting new series of postings. Of course, I see a lot of published research in the Japanese engineering press, particularly the welding! I must try to remember when I spot something that is markedly innovative.

  2. I’m glad you think it’s interesting.

    I’m not sure that engineering innovation would shake the perception, though. That’s what the Japanese are supposed to be good at, after all, and, of course, engineering isn’t fundamental science. Never mind all the false assumptions about engineering that contains.

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