DNA could modify itself with no outside help, say biologists

Princeton University ^ | March 28, 2006 | Chad Boutin

[SampleMan]

Spirals of DNA, once thought to be merely the passive memory banks that preserve life’s blueprints, may also actively modify themselves under certain conditions, according to Princeton University scientists.

A team of molecular biologists has found that some single strands of DNA are capable of removing a genetic building block from the spiral, a task previously thought to be impossible without the involvement of a separate catalyst such as RNA or proteins. Such removal, called depurination, occurs only at a single point within a particular genetic sequence, one that appears at least 50,000 times in the human genome. The team’s discovery that the removal occurs consistently in laboratory samples indicates that DNA is a more dynamic substance than was previously thought, and it raises the possibility that other unexpected behaviors still await discovery in this well-studied molecule.

“No one ever dreamed genomic DNA may have another function besides memory storage, but it apparently does,” said Jacques Fresco, the Damon B. Pfeiffer Professor in the Life Sciences at Princeton. “We don’t really know yet why or how it happens, but it makes us wonder what else DNA might be doing without our knowledge.”

Dr. Ann Skalka, senior vice president for basic science at the Fox Chase Cancer Center in Philadelphia, said the findings merit continued attention.

“This fascinating and unanticipated new property of DNA has the potential to cause substantial damage to our cells, leading to cancer or other diseases, unless it is controlled or exploited for some beneficial purpose,” she said. “We will stay tuned.”

Fresco’s team published its findings in the March 21 issue of the journal, Proceedings of the National Academy of Sciences. Also contributing to the research are Princeton researcher Olga A. Amosova and Richard Coulter, currently at West Chester University.

The double-stranded helical structure of DNA is a shape familiar to many, and these long, stringy molecules are in most circumstances unchanging and highly stable -- valuable characteristics for objects whose function is to preserve the master plan of the organism that carries them. Altering the sequence of a DNA strand is often necessary for innumerable bodily functions, such as growth and healing, but scientists previously thought that such alterations require other chemical catalysts or enzymes to do the clipping and rearranging.

When DNA does undergo such changes, its two strands sometimes separate from one another like a broken zipper splitting down the middle, the teeth of one side pulling away from the other. But in some cases, each side will then often bunch up so its teeth can latch on to others from the same side, forming small “loops” of a single-stranded DNA that extend out from the side of the double-stranded helix’s “stem.”

“For genes to express themselves and create change within the body, you absolutely have to get the two strands of DNA apart first, and it’s only through separation that DNA forms these stem-loops,” said Amosova, a research molecular biologist and Fresco’s long time collaborator. “Such separation occurs, for example, when genes are doing something to regulate the body.”

But the team found that if a stem-loop forms from a particular sequence of DNA, one of the genetic “teeth” will fall spontaneously from that side of the zipper, and the weakened strand will eventually break apart in that spot unless it is repaired by enzymes in the cell. Fresco said this sort of activity seems akin to self-mutilation at first glance.

“To a scientist, this kind of self-inflicted genetic damage appears unhealthy, the sort of thing that would cause undesirable mutations and could kill off the organism,” Fresco said. “Cells have evolved a complex DNA repair system to constantly repair such damage. But evolution has not, as we’d expect, put a stop to it. So we theorize it must be happening for some good reason that we have yet to uncover.”

Of the more than 3 billion DNA building blocks in the human genome, the 18-residue sequence that gives rise to the cleavage occurs in about 50,000 places -- a very significant number, Fresco said.

“We can only speculate now as to what aspects of biology this self-cleavage could influence, but the general function of stem-loops combined with the number of sites where depurination can occur does make us curious enough to look further,” Amosova said. “Such a self-depurination capability may, for example, be beneficial in sections of the genome involved in antibody production, where losing a building block from the sequence could lead to higher mutation rates in the antibody-coding genes. This, in turn, could lead to a larger variety of antibodies to protect the body more effectively.”

More generally, Amosova said, losing a building block increases the flexibility of the otherwise highly rigid DNA molecule, which in some circumstances needs to be bent.

“Flexibility could help with DNA packaging, which happens any time you need to stuff DNA into a tight place,” she said. “In particular, viruses typically pack a lot of DNA strands into their shells, leaving virtually no space unused. It may also play a role in the folding of DNA in chromosomes.”

Still, Fresco said, it remains too early to tell where the discovery will lead, though the team will look for some possible biological role for their finding.

“Thus far we have observed this effect under laboratory conditions that closely resemble those within the cell. Now, we would like to observe them directly in the cell nucleus,” he said. “If we have indeed found one way that DNA can change itself spontaneously, there might be others, and we plan to hunt for them.

“Additionally, I might mention that this discovery was made while we were exploring ways to repair the genetic mutation that causes sickle cell anemia,” Fresco said. “We noticed that the depurination occurs right next to the site of the mutation responsible for the disease, but we don’t yet know if there’s any relation between these two facts. We certainly hope we’ve noticed an effect that will eventually offer some new approaches to many diseases.”

[WKB]

I still do not understand how not attempting to convert you has caused distress.


I WAS JOKING
You really don't have a sense of humor do you??

[RunningWolf]

WKB

Don't reply to 3 dogs crapping, he is about as much to honest dialog as demented is, IOW XERO

Now as you see they will never say or own up to their agendas, even though it is as plain as day the hatred for people of faith that flows out from them, therefore it becomes very easy for them to make all sorts of accusations to you as you see now happening.

Wolf

[RunningWolf]

Well here is your chance.

Just what are your motives and agendas?

I can see what it looks like, but lets hear it straight from Demented.

Now don't run off now like you always do.

Wolf

[CarolinaGuitarman]

" Don't reply to 3 dogs crapping, he is about as much to honest dialog as demented is, IOW XERO."

You're not as bad as all that; he can still post to you if he wants. :)


I am SO pleased to have touched you so deeply, Mordo. :)

[Lurking Libertarian]

Specifically Hyers argues that Genesis 1 & 2 is principally a polemic against the surrounding polytheistic cultures. The point isn't chronology, science, etc, but rather emphasizing that stars, planets, sun, moon etc are created things; not gods or some other sort of divine, sacred entities as in the polytheistic scheme.

An excellent point. The same type of reasoning explains, IMHO, why the story of Noah is so much like the flood story in the Epic of Gilgamesh in its details, yet so unlike it in its message.

[cccp_hater]

"There are NO good mutations."

If you are trying to say that every mutation is deleterious you are simply incorrect. Though the majority of mutations are deleterious (lethal mutations are fairly rare)to the fitness of the organism, neutral mutations also make up a large percentage of total mutations. Adaptive mutations, though rare, do in fact occur at a fairly high rate when given the population sizes (billions/trillions of organisms) usually discussed in the natural world.

[ml1954]

I still do not understand the motive behind your blank replies.

My guess...blank replies come from a blank mind that wants to reply but can't formulate a better reply that nothing.

[RunningWolf]

3 dogs crapping,

You are about as insignificant and obnoxious as those images you like to put up on this forum. If you think they really bother me and or you can put them up with no consequence, go for it, the images are yours.

Wolf

[CarolinaGuitarman]

"3 dogs crapping..."

You're talking to yourself again Mordo.

" If you think they really bother me and or you can put them up with no consequence, go for it, the images are yours."

Nice try. The images of you are stuck in your brain, that's good enough for me. It's all you talk about. I won. :)

[patriot_wes]

"Of the more than 3 billion DNA building blocks in the human genome, the 18-residue sequence that gives rise to the cleavage occurs in about 50,000 places "

cleavage...did you say cleavage, I'm all ears....er eyes...pictures please...

[patriot_wes]

"Of the more than 3 billion DNA building blocks in the human genome, the 18-residue sequence that gives rise to the cleavage occurs in about 50,000 places "

cleavage...did you say cleavage?, I'm all ears....er eyes...pictures please...

[RunningWolf]

Your victories like your science has an existence only in the dream fantasy of its cult followers. But take your victories where you can.

Wolf

[CarolinaGuitarman]

"Your victories like your science has an existence only in the dream fantasy of its cult followers. But take your victories where you can."

Proving my point, Mordo. :)

[WKB]

It's not nice to talk about people behind
their back.
But there's no reason to expect any less.

[RunningWolf]

Nice try? Talking to ones self? Whats that about?

Its your work as it were, and you posted it to me. And it is not all I talk about.

Just what kind of nut-ball fantasy world do you live in 3dogs crapping?

Man you are one goofy *** 3dogs, just like several of the other weird characters that this godless hate filled cult attracts to it. It fits you guys like a glove.

Actually this is not to the whole group, but if I don't paint with a broad brush, it might be seen by ****** as a 'personal attacks' at the evos. So you, Sjive, Bwag, etc carry on with your poison agenda.

Do it for the lurkers /sarc> what a maroon!



Wolf

[ml1954]

You respond with blank responses. You routinely insult those you don't agree with. You've admitted to trying to be an antagonizing troll. And you lecture me on what's not nice and posting etiquette. Spare me your hypocrisy.

[WKB]

You respond with blank responses. You routinely insult those you don't agree with. You've admitted to trying to be an antagonizing troll. And you lecture me on what's not nice and posting etiquette. Spare me your hypocrisy.



Well, At least I have enough guts to do it to their
face. I don't post about people to other people
in hopes they won't see it and be called on it.
And BTW trolls don't last 7 and 1\2 years on FR.

[R. Scott]

Apparently not all the scientists at Princeton are drinking the "everything there is to know about evolution is already known" Kool-Aid.

I thought the "everything there is to know about evolution is already known" crowd was limited to the creationists.

[ml1954]

I don't care how long you've been here. You admitted to trolling and not bothering to try to post anything of substance ...

http://www.freerepublic.com/focus/f-news/1593422/posts?page=167#167

...and then you try to lecture me on posting etiquette. That's rich.

[WKB]

That's rich.




I just wish I was.