Skip to comments.Ultra-sensitive microscope reveals DNA processes
Posted on 11/16/2005 3:40:35 AM PST by snarks_when_bored
* 14:02 15 November 2005
* NewScientist.com news service
* Gaia Vince
A new microscope sensitive enough to track the real-time motion of a single protein, right down to the scale of its individual atoms, has revealed how genes are copied from DNA a process essential to life.
The novel device allows users to achieve the highest-resolution measurements ever, equivalent to the diameter of a single hydrogen atom, says Steven Block, who designed it with colleagues at Stanford University in California.
Block was able to use the microscope to track a molecule of DNA from an E.coli bacterium, settling a long-standing scientific debate about the precise method in which genetic material is copied for use.
The molecular double-helix of DNA resembles a twisted ladder consisting of two strands connected by rungs called bases. The bases, which are known by the abbreviations A, T, G and C, encode genetic information, and the sequence in which they appear spell out different genes.
Every time a new protein is made, the genetic information for that protein must first be transcribed from its DNA blueprint. The transcriber, an enzyme called RNA polymerase (RNAP), latches on to the DNA ladder and pulls a small section apart lengthwise. As it works its way down the section of DNA, RNAP copies the sequence of bases and builds a complementary strand of RNA the first step in a new protein.
For years, people have known that RNA is made up one base at a time, Block says. But that has left open the question of whether the RNAP enzyme actually climbs up the DNA ladder one rung at a time, or does it move instead in chunks for example, does it add three bases, then jump along and add another three bases.
Light and helium
In order to settle the question, the researchers designed equipment that was able to very accurately monitor the movements of a single DNA molecule.
Block chemically bonded one end of the DNA length to a glass bead. The bead was just 1 micrometre across, a thousand times the length of the DNA molecule and, crucially, a billion times its volume. He then bonded the RNAP enzyme to another bead. Both beads were placed in a watery substrate on a microscope slide.
Using mirrors, he then focused two infrared laser beams down onto each bead. Because the glass bead was in water, there was a refractive (optical density) difference between the glass and water, which caused the laser to bend and focus the light so that Block knew exactly where each bead was.
But in dealing with such small objects, he could not afford any of the normal wobbles in the light that occur when the photons have to pass through different densities of air at differing temperatures. So, he encased the whole microscope in a box containing helium. Helium has a very low refractive index so, even if temperature fluctuations occurred, the effect would be too small to matter.
One by one
The group then manipulated one of the glass beads until the RNAP latched on to a rung on the DNA molecule. As the enzyme moved along the bases, it tugged the glass bead it was bonded too, moving the two beads toward each together. The RNAP jerked along the DNA, pausing between jerks to churn out RNA transcribed bases. It was by precisely measuring the lengths of the jerks that Block determined how many bases it transcribed each time.
The RNAP climbs the DNA ladder one base pair at a time that is probably the right answer, he says.
Its a very neat system amazing to be able see molecular details and work out how DNA is transcribed for the first time, said Justin Molloy, who has pioneered similar work at the National Institute for Medical Research, London. Its pretty incredible. You would never have believed it could be possible 10 years ago.
Journal reference: Nature (DOI: 10.1038/nature04268)
As an aside, note that the RNA polymerase, once brought into contact with the DNA strand, simply begins its replicative journey, moving along the strand one base pair at a time (as the experiment apparently demonstrates for the very first time). Now why does the RNA do this? Nobody (in their right mind) would suggest that it has a will and is acting intentionally, or that some unseen deity's hand is continually pushing it along, so it must be acting as its chemical structure compels it to act. This base-pair by base-pair copying motion must simply be what the chemical structure of RNA does. So why this chemical structure and not some other? This is a question that doesn't appear to lend itself to a scientific answer. Perhaps an ID'er would suggest that a higher intelligence designed the chemical structure of RNA to do just what it does. That may or may not be, but, clearly, it's not an hypothesis of empirical science. As a consequence, prolonged examination of such a hypothesisas if it were a scientific hypothesishas absolutely no place in a science classroom.
The more we learn about the microscopic world, the less likely it seems that non-physical (or non-mathematical) principles are needed to explain its behavior.
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God built the RNA-DNA engine. A very beautiful thing.
Holy Cow! That is awesome!
Do I see cloning as a common reality coming?
Me thinks so ... .
I'm not convinced knowing how this works will lead to good things considering the mindset of MANY in the field of science.
God built the RNA-DNA engine.
You may be right, of course, but the notion isn't scientific and oughtn't to be taught as such (which, of course, was the point of my little aside).
A very beautiful thing.
Dang, Junior! Hadn't seen that.
What concerns me is how the godless will use this information. There is no honor amongst them ... . Ethics are not present either.
This is far from true, as some thought and some attention to history would show. And (by way of anecdote) don't forget that the BTK monster was a well-respected Lutheran congregant...
Slick, indeed. A kind of Glasperlenspiel. Hesse might have been pleased.
I hear that often. Is it true?
For since the creation of the world God's invisible qualitieshis eternal power and divine naturehave been clearly seen, being understood from what has been made, so that men are without excuse. (Romans 1:20)
Perhaps an ID'er would suggest that a higher intelligence designed the chemical structure of RNA to do just what it does.
Perhaps a scientist will be able to show how something OTHER than a copy manages to get into the strand.
Since this is the very essence of Evolution, THAT is what is needed now to blast the IDer's out of the water.
By what authority do you give this answer?
Actually the molecular transactions have been hypothesized, this IS the empirical data that was required to validate said hypothesis. I am digging the paper out form our faculty archive.
Call me stupid if you want (I think ignorant is the right word, stupid) but what am I supposed to be astonished about, the experiement or the results?
I am tempted to agree with you on this one (BTW anyone attacks me I am a catholic)
As to your other point, the copying process is always prone to error (there's a whole lotta shaking going on down there). Most of the errors don't improve the fitness of the resulting organism, but some do. Hence the show goes on.
Thanks for the ping!
I wasn't writing a treatise, nor is my concluding sentence intended to be a deduction from the remarks of the preceding paragraph. If you'd care to specify what it is that I've said that is mistaken, I'll be glad to hear it.
I cannot agree with that at all, otherwise the entire field of molecular-biology would be redundant. Please do not assume that much of what you consider "unknown" is indeed the case
It's been my experience that the only thing proved by the "godfull" describing the supposed lack of honor, ethics and morals in the "godless" is the intellectual and emotional depravity of those very same "godfull" people. Those that make such claim about the "godless" are only proving that they, themselves, are without honor, ethics and morals.
How does anyone look at the wonder of DNA and think "invisible sky-god"?
And anybody who reads your post and is not offended is either stupid or not paying attention. Maybe I haven't had my coffee yet. Arrogant twerp.
Molecular chemists and biologists try to determine the structures and functions of the molecules and molecular assemblages that they study. If you maintain that they're also trying to give reasons (in the sense of final causes) for their results, you'll have to give me some references.
a few years ago by a breakthrough by a Doctor called dorothy erie,where she described her collaborative paper identifying new an as yet undiscovered additional binding site for the RNAP enzyme, which we call an allosteric site. As I said I would dig out this reference and I have. This white paper described in full a methodology that proved her hypothesis concerning genetic expression and the precise specification of molecular transactions etc.
The experiment you refer to here has created a corroborative methodology and an observable confirmation of her results, that is all.
Whaaaat? How on earth could any etiological analysis that is attempting to determine a causative agent for a disease NOT proceed on this assumption?
You're quite right to rebuke me for my beginning sentence. It was poorly stated and insensitive, and I apologize to you and to all readers of this thread for having written it.
Ah, here's the rub. Science asks "how," not "why."
Since this is the very essence of Evolution, THAT is what is needed now to blast the IDer's out of the water.
By this standard, ID has already been blown out of the water. The error rates of DNA replication and polymerase transcription are well known, as are the types of errors and how they occur. Errors occur in the transcription of one out of every 10^4 to 10^5 base pair. DNA replication has an error rate that is approximately the same, but the DNA strand is checked twice for errors which increases accuracy. Note that I am talking about errors in the chemical assembly of proteins and the duplication of DNA. This does not include damage from environmental sources such as chemical carcinogens or radiation exposure, only errors in the transcription and duplication process.
thanks for the post
"This is far from true, as some thought and some attention to history would show. And (by way of anecdote) don't forget that the BTK monster was a well-respected Lutheran congregant..."
Yes and the A bomb is well respected too, or it better be!
A good definition of the mutability statistic
The work of Dr. Erie sounds interesting. I don't see that anything I wrote has any bearing on it.
because you probably read just an abstract it was over 12,000 words in PDF
Apology accepted. :-) And yes, it is a fascinating article. Thanks for posting it.
I'm impressed. I have trouble with with tiny screws on glasses.
"Why?" is often answered with "because." This is well within bounds for science. By whose authority are the limits of scientific inquiry set?
Still, given that both molecules were attached to big glass beads, one has to wonder whether the results were affected by that fact. It sorta sounds like asking somebody to enter a race dragging a ball and chain -- would you expect him to compete differently?
Would an unencumbered RNAP behave the same way? Or would it be able to leap up the ladder in chunks?
Yes, let's immediately get offended instead of trying to understand what is being presented - that always helps to improve a situation...
Your timely and humble apology is a breath of fresh air. May God ever bless you, dear snarks_when_bored.
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