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DNA could modify itself with no outside help, say biologists
Princeton University ^ | March 28, 2006 | Chad Boutin

Posted on 03/29/2006 1:47:22 PM PST by 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.”


TOPICS: News/Current Events
KEYWORDS: biology; dna; evolution
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To: AntiGuv

LOLOL!


21 posted on 03/29/2006 3:13:26 PM PST by phantomworker (You are what you think you are......Qu’est que c’est)
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To: SampleMan
>DNA could modify itself ...

Maybe DNA
has a sense of humor and
is effing with us . . .

22 posted on 03/29/2006 3:18:52 PM PST by theFIRMbss
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To: peyton randolph
>Maybe it is Xenu attacking your thetans




"Hey. Is that a joke?
Do I look like I'm laughing?
Life is serious.

Can we talk a bit?
Hey, don't push. Can I leave you
some literature . . ."

23 posted on 03/29/2006 3:22:49 PM PST by theFIRMbss
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To: PatrickHenry

Very curious. Thanks for the ping.


24 posted on 03/29/2006 3:29:30 PM PST by The_Victor (If all I want is a warm feeling, I should just wet my pants.)
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To: SampleMan
I just can't resist another juicy evolution story. Apparently not all the scientists at Princeton are drinking the "everything there is to know about evolution is already known" Kool-Aid.

What an irresponsible thing to say. Your B.S. theory on how science works and how scientists work is just plain wrong. Science is properly set up so that no scientific theory is absolute unlike your absolute belief that Genesis is absolutely correct no matter what.

25 posted on 03/29/2006 3:31:02 PM PST by hawkaw
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To: timburton; Ichneumon
There are NO good mutations.

A vast range of scientific Information to the contrary, courtesy Ichneumon

Directed evolution of biosynthetic pathways. Recruitment of cysteine thioethers for constructing the cell wall of Escherichia coli

Directed evolution of a type I antifreeze protein expressed in Escherichia coli with sodium chloride as selective pressure and its effect on antifreeze tolerance

Molecular evolution of an arsenate detoxification pathway by DNA shuffling

Long-term experimental evolution in Escherichia coli. XIII. Phylogenetic history of a balanced polymorphism

Rates of DNA sequence evolution in experimental populations of Escherichia coli during 20,000 generations

The evolutionary origin of complex features

Contribution of individual random mutations to genotype-by-environment interactions in Escherichia coli

Rapid phenotypic change and diversification of a soil bacterium during 1000 generations of experimental evolution

Bacterial evolution and the cost of antibiotic resistance

The ecology and genetics of fitness in Chlamydomonas. IX. The rate of accumulation of variation of fitness under selection.

Mild environmental stress elicits mutations affecting fitness in Chlamydomonas

The emergence and maintenance of diversity: insights from experimental bacterial populations

Direct Estimate of the Mutation Rate and the Distribution of Fitness Effects in the Yeast Saccharomyces cerevisiae

Pleiotropic effects of beneficial mutations in Escherichia coli

The Rate of Compensatory Mutation in the DNA Bacteriophage X174

Mutation-selection balance accounting for genetic variation for viability in Drosophila melanogaster as deduced from an inbreeding and artificial selection experiment

Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene

Complete Rescue of Lipoprotein Lipase–Deficient Mice by Somatic Gene Transfer of the Naturally Occurring LPLS447X Beneficial Mutation

Evolution and Information: The Nylon Bug

Spontaneous mutations in diploid Saccharomyces cerevisiae: more beneficial than expected

Nonuniform concerted evolution and chloroplast capture: heterogeneity of observed introgression patterns in three molecular data partition phylogenies of Asian Mitella (saxifragaceae)

Evolutionary analysis of genetic variation observed in citrus tristeza virus (CTV) after host passage

Examples of Beneficial Mutations and Natural Selection

Genetic Variant Showing a Positive Interaction With ß-Blocking Agents With a Beneficial Influence on Lipoprotein Lipase Activity, HDL Cholesterol, and Triglyceride Levels in Coronary Artery Disease Patients

Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene

Evolution of new information

Spontaneous mutations in diploid Saccharomyces cerevisiae: more beneficial than expected

Are Mutations Harmful?

Evolution and Information: The Nylon Bug

Directed evolution of human estrogen receptor variants with significantly enhanced androgen specificity and affinity

Multiple duplications of yeast hexose transport genes in response to selection in a glucose-limited environment

Complete Rescue of Lipoprotein Lipase–Deficient Mice by Somatic Gene Transfer of the Naturally Occurring LPLS447X Beneficial Mutation

Punctuated evolution caused by selection of rare beneficial mutations.

PLEIOTROPIC EFFECTS OF BENEFICIAL MUTATIONS IN ESCHERICHIA COLI

The Distribution of Fitness Effects Among Beneficial Mutations

Incidentally, there is no law that says the entropy of DNA can't decrease through time.

26 posted on 03/29/2006 3:35:25 PM PST by Quark2005 (Confidence follows from consilience.)
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To: theFIRMbss
Can I leave you
some literature . . .

ROTFLMAO.

 

27 posted on 03/29/2006 3:43:23 PM PST by peyton randolph (As long is it does me no harm, I don't care if one worships Elmer Fudd.)
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To: bobdsmith
no scientist has ever claimed such a thing period

True, of course. But perhaps it would be better if you paid no attention to the flaming troll...

28 posted on 03/29/2006 3:45:37 PM PST by balrog666 (Irrational beliefs inspire irrational posts.)
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To: SampleMan
“This fascinating and unanticipated new property of DNA has the potential to cause substantial damage to our cells...."

Sounds like a pessimistic democrat..The glass is half empty.

I prefer to be optimistic that this may be the key to the evolution of species whether under the direction and control of a higher being, or not....as you prefer to believe.

29 posted on 03/29/2006 3:48:58 PM PST by Rapscallion (Democrats: Supporting the conquest of America since VietNam.)
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To: SampleMan
Apparently not all the scientists at Princeton are drinking the "everything there is to know about evolution is already known" Kool-Aid.

I was unaware that any leading scientists have made such a claim. Do you have a reference?
30 posted on 03/29/2006 3:51:14 PM PST by Dimensio (http://angryflower.com/bobsqu.gif <-- required reading before you use your next apostrophe!)
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To: timburton
Looks like the Law of Entropy strikes again, and the biggest objection (apart from irrationality of matter being eternal) to genetic evolution stays.

What, exactly, does the "Law of Entropy" state?

There are NO good mutations

I am afraid that your claim is demonstratably false.
31 posted on 03/29/2006 3:52:28 PM PST by Dimensio (http://angryflower.com/bobsqu.gif <-- required reading before you use your next apostrophe!)
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To: SampleMan
not all the scientists at Princeton are drinking the "everything there is to know about evolution is already known" Kool-Aid.

Could you point us to a list of those who claim we know everything? Thanks

32 posted on 03/29/2006 3:54:30 PM PST by Virginia-American
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To: SampleMan

Great post. Thank you. Let the debate begin again.


33 posted on 03/29/2006 3:55:17 PM PST by Rapscallion (Democrats: Supporting the conquest of America since VietNam.)
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To: Quark2005
Why did you double-post the nylon bug?

Let me guess, "Nothing beats a great pair...of L'Eggs!"

Cheers!

34 posted on 03/29/2006 4:34:26 PM PST by grey_whiskers (The opinions are solely those of the author and are subject to change without notice.)
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To: SampleMan
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.

Reminds me of how often the crevo threads themselves "unwind" over time ;-)

(Heads for exit, running for cover...)

Cheers!

35 posted on 03/29/2006 4:37:26 PM PST by grey_whiskers (The opinions are solely those of the author and are subject to change without notice.)
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To: Virginia-American
Could you point us to a list of those who claim we know everything? Thanks

There's a list? Its worse than I thought.

36 posted on 03/29/2006 4:39:06 PM PST by SampleMan
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To: grey_whiskers
Why did you double-post the nylon bug?

Must be a "bug" in my coding. : )

37 posted on 03/29/2006 4:46:25 PM PST by Quark2005 (Confidence follows from consilience.)
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To: Dimensio
I was unaware that any leading scientists have made such a claim. Do you have a reference?

I can point you to a leading Korean scientist that's good at cloning, or perhaps you're interested in claims of cold fusion?

Gosh, you got me. I don't have a quote of a "leading scientist" saying, "I declare that there is nothing more to learn about evolution." However, finding a lot of quotes that say the equivilent of, "What total nonsense, shut up" isn't that difficult. I believe that's pretty much been the line on contrary scientific thought since about 50 A.D.

38 posted on 03/29/2006 4:49:37 PM PST by SampleMan
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To: SampleMan
" I can point you to a leading Korean scientist that's good at cloning, or perhaps you're interested in claims of cold fusion?"

You mean those people said that,

"everything there is to know about evolution is already known"?

That's odd. Evolution had nothing to do with their fields. I am sure you can provide documentation though, you wouldn't just make things up...


" However, finding a lot of quotes that say the equivilent(sic) of, "What total nonsense, shut up" isn't that difficult."

Then produce them.
39 posted on 03/29/2006 4:55:34 PM PST by CarolinaGuitarman ("There is grandeur in this view of life...")
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To: SampleMan

So you just made it up, the part about science claiming to know everything.


40 posted on 03/29/2006 4:56:25 PM PST by js1138 (~()):~)>)
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