Darwin's Radio: Prehistoric Gene Reawakens to Battle HIV -A Galaxy Classic
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August 06, 2009

Darwin's Radio: Prehistoric Gene Reawakens to Battle HIV -A Galaxy Classic

Darwinsradio_full 'The next great war will start inside us. 'In the next stage of evolution, mankind is history'.

Greg Bear, Darwin's Radio

About 95% of the human genome has once been designated as "junk" DNA. While much of this sequence may be an evolutionary artifact that serves no present-day purpose, some junk DNA may function in ways that are not currently understood. The conservation of some junk DNA over many millions of years of evolution may imply an essential function that has been "turned off." Now scientists say there's a junk gene that fights HIV. And they've discovered how to turn it back on.


What these scientists have done could give us the first bulletproof HIV vaccine. They have re-awakened the human genome's latent potential to make us all into HIV-resistant creatures; they published their ground-breaking research  in PLoS Biology.

A group of scientists led by Nitya Venkataraman and Alexander Colewhether wanted to try a new approach to fighting HIV - one that worked with the body's own immune system. They knew Old World monkeys had a built-in immunity to HIV: a protein called retrocyclin, which can prevent HIV from entering cell walls and starting an infection. So they began poring over the human genome, looking to see if humans had a latent gene that could manufacture retrocyclin too. It turned out that we did, but a "nonsense mutation" in the gene had turned it off at some point in our evolutionary history.

Nonsense mutations are caused when random DNA code shows up in the middle of a gene, preventing it from beginning the process of manufacturing proteins in the cell. Venkataraman and her team decided to investigate this gene further, doing a series of tests to see if the retrocyclin it produced would keep HIV out of human cells. It did.

At last, they knew that if they could just figure out a way to reawaken the "junk" gene that creates retrocyclin in humans, they might be able to stop HIV infections. The researchers just needed to figure out a way to remove that nonsense mutation and get the target gene to start manufacturing retrocyclin again.

Here's where things really get interesting. The team found a way to use a compound called aminoglycosides, which itself can cause errors when RNA transcribes information from DNA to make proteins. But this time, the aminoglycoside error would work in their favor: It would cause that RNA to ignore the nonsense mutation in the junk gene, and therefore start making retrocyclin again. In preliminary tests, their scheme worked. The human cells made retrocyclin, fended off HIV, and effectively became AIDS-resistant. And it was done entirely using the latent potential in the so-called junk DNA of the human genome.

After more research is done, the researchers believe this might become a viable way to make humans immune to HIV infection.

What's especially intriguing, beyond the amazing idea of an AIDS vaccine, is that aminoglycosides have the potential to unlock the uses for other pieces of junk DNA.  In Darwin's Radio, certain portions of these "non-sense" sequences, remnants of prehistoric retroviruses, have been activated by aminoglycosides
In the novel, humans start rapidly evolving after their junk DNA re-awakens in response to stress. Could we induce instant mutations, or gain other new immunities by using aminoglycosides on our junk DNA?

via PLoS Biology

Posted by Casey Kazan.

Related Galaxy posts:

Did Ancient Viruses Spur Human Evolution? A Galaxy Insight
"Voyage of the Beagle 2" -The Search for Microbial DNA
“Playing God” -Scientists in Final Stage of Creating Man-made Life
Darwin's Lab: Scientists on Brink of Creating Life

Comments

Fantastically powerful stuff, thus capable of immense disaster if we're not careful. I'm not saying to stop it - in fact, I say go for it. But we should be careful in our assumptions when so much of our progress lacks a great deal of data, or ignores massive swaths of it even when available, due to either our inability to understand that data and/or our desire to only obtain a certain outcome.

This could turn out to be a fantastically elegant solution to the HIV problem.

However, I would be interested to know how they determine that what turned this gene off was a 'nonsense mutation'... Given how little we truly understand about the inner workings of the cell at the molecular level, we should be very careful to ensure that bypassing this nonsense mutation, which is apparently not so nonsense as to affect the entire human race, surviving all evolutionary steps since its appearance, doesn't enable (or disable) something else.

Also, is it perhaps wise to not dismiss part of our DNA as 'junk' when our only reason for doing so is we do not understand what it is for? It should be labelled 'intriguing set of possibilities we should investigate'

Awesome! Thanks!

How is the aminoglycosides targeted at the specific sequence coding for retrocycling?

retrocyclin*

nice link to the original article...

Let the 2nd sexual revolution begin!

I agree with the first two comments. Remember the film "I am Legend"? well messing around with DNA that we have very little clue on could spark off something similar to the events that are shown in the flash backs of the film.

I think they should be extremely cautious in what they decide "re-mutate"

I am legend was a film idiot

Just a note on the book for those who love to read. Those who have not read the book Darwin's Radio, I suggest you do so when you have the time to site down and devour both it and its sequel Darwin's Children. Both get high marks in readability and for the science part of science fiction, but be prepared for two very different books. Where Darwin's Radio stands alone just fine and speculates about good science theory, Darwin's Children gave a very eerie prediction to what happens when you unleash the government on public fears. Darwin's Children could have easily been written post Bush (43) admin, and all I can say is thankfully no one behind that machine was smart enough to read this little horror story.

Youd think theyd be able to make a type of virus which removed this peice of the dna from cells and made new ones with the "upgraded" dna.

To answer the second poster they know it is a nonsense gene as it is the entire gene for retrocyclin with a spurious 3 basepair addition. It is thus very clear that it was once a working gene but an insertion mutation in our past knocked it out.

Secondly you could be changing DNA probably by injection. If the mutation went bad the injectee would in all likelihood just die or slightly over express something. The chance of you causing a chance mutation that makes him into a super strong, sunlight adverse, monster are, well, not so big. [Plus you should read the book which has a totally different and much more sensible ending.]

AIDS stands for Acquired Immune Deficiency Syndrome. AIDS is a serious condition that weakens the body's immune system, leaving it unable to fight off illness.

AIDS is the last stage in a progression of diseases resulting from a viral infection known as the Human Immunodeficiency Virus (HIV or AIDS virus). The diseases include a number of unusual and severe infections, cancers and debilitating illnesses, resulting in severe weight loss or wasting away, and diseases affecting the brain and central nervous system.

Missing from the article (but possibly existing in the literature) is a theory about how this silenced gene increased fitness in the population where it originated. What factor in the environment of the first phenotype selected for this change? Second, why then did it spread to a much larger population?

The environmental factor may be greatly diminished presently but at one time must have been pervasive. The other possibility could be that this silent gene was a free rider along with another modified gene that improved fitness. The bottom line is not zombies run amuk but that once upon a time silencing the gene went along with improved fitness.

The bottom line is not zombies run amuk but that once upon a time silencing the gene went along with improved fitness.

Sounds like something you'd hear about in a movie.


Your article is useful

Hello Radio: Prehistoric Gene Reawakens to Battle HIV
-A Galaxy Classic is a classic indeed some people tell my that is not good and i think that they are wrong that they will never be a clssic and i think different i think that is a nice radio .

@Kirk-
That's a fairly common fallacy about evolution; namely, that all mutations must have a positive effect on natural selection or they'd be weeded out.

Retrocyclin appears to specifically block SIV and HIV, without exposure to either, the mutation that disables it is neither selected for or against. However, the population in which the mutation occurred likely had other factors influencing that selection.

Look at the genes that code for the production of vitamin C in apes. Broken by a single error, and yet this error is present in multiple distinct species. Due to the diet of the common origin, this most likely had no real effect on reproductive fitness. That doesn't mean we derive benefit from the inability to produce vitamin C ourselves.

It'd be good to see some major progress in battle of HIV, too many people catch it so easily...

That's excellent that you share so many marvellous facts and new fresh points.

The diseases include a number of unusual and severe infections, cancers and debilitating illnesses, resulting in severe weight loss or wasting away, and diseases affecting the brain and central nervous system.

I recently came across your blog and have been reading along. I thought I would leave my first comment. I don't know what to say except that I have enjoyed reading. Nice blog. I will keep visiting this blog very often

HIV is really a serious threat to the world and its very severe.Hope more people sees this post and get benefit.Meanwhile keep up your great work

i think you have a great site here... today was my first time coming here.. i just happened to find it doing a google search. anyway, great post.


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