[kalimna (OP)]

Greetings all,
My first post on this here (very interesting) forum, and a thought which occurred to me whilst reading Dawkins' Selfish Gene (for about the 3rd time) and Ridleys' Nature vs Nuture. And apologies if this has been covered elsewhere.

To build up a protein, a piece of RNA needs to be transcoded from the original DNA. And this is controlled by various other proteins etc (I dont really know the details, and for my question Im not sure that they are wholly important). To produce this RNA, the original DNA needs to be 'unzipped', correct? Now, the point of all this rambling is - how does the transcoding machinery 'know' which of the 2 DNA strands are to be coded? I know that the strands are complementary, but they are different.
Anyhoo, just wondering.

Cheers,
Adam

[neilep]

Greetings all,


Cheers,
Adam

HI Adam,

WELCOME !!..the above is the only part of your post that I understand !!  LOL []..but then I'm no academic here...just wanted to say ' Hello ' and hope you enjoy the site.

best Wishes

Neil

[kalimna (OP)]

Howdy,
Thanks for the greets. I prob wasnt making too much sense as am currently in the middle of packing up a house to move this weekend and my head is full of cardboard boxes and brown tape.
Good site so far

Adam

[neilep]

Howdy,
Thanks for the greets. I prob wasnt making too much sense as am currently in the middle of packing up a house to move this weekend and my head is full of cardboard boxes and brown tape.
Good site so far

Adam

Oh boy !

Good luck with the move !!..Prepare for some stress !!

D'ya want a hand !! ?..I'll drive up from London and drop wifey off to help you carry stuff !!..LOL..actually I'll just stick her on a train !  []

Sorry...don't mean to sidetrack this thread !..I hope you get some responsible comments...it can take a while but bear with us !

[kalimna (OP)]

Heh heh. No probs - thanks for the offer of your wife. Not sure if she would agree, but who knows?
And after the 1 1/2 hr drive of 14.4 miles, I could take a lack of responsibility
Or maybe just a glass of red wine........

[WylieE]

Hi Adam,
  So I guess it's OK since you're a newbie poster to have a newbie to answer- so this is my first post other than a lame joke somewhere else. 
Here goes:
First the background (which you probably already know)
A DNA strand has directionality.  Nucleotides can form a chain in a head to tail type manner, they can't be put together head to head or tail to tail.  One end is called the 3' end because it ends with (aka has free) the hydroxyl on the 3' position of the sugar ring -let's call this the head.  The other end is called the 5' end because it ends (has free) the group on the 5' position of the sugar ring, often a phosphate group, we can call this the tail.  Now, if you look at a piece of double stranded DNA each strand will have opposite directions one going 5' to 3' and the other strand going 3' to 5'. For some reason I like to imagine turtles going head to tail, if we use this picture, by convention the turtles would be drawn facing to the right on the top strand and to the left on the bottom strand.  Why on earth would we care which way the turtles are facing? 
The answer to your question is that polymerase can only go in one direction.  It can only add a new nucleotide to the growing strand at the 3' end.  It can only put a new RNA turtle in front of another turtle (It can't add one to the tail of a turtle in front).  So it always reads the DNA from 3' to 5' and makes an RNA chain in 5' to 3' direction.
(confused yet?- this would be easier if I knew how to put pictures in a post I'll  figure that out tomorrow)
 So it depends on which direction the polymerase is facing.  If the polymerase sits down on the DNA facing to the right it will read the bottom strand (the one going 3' to 5' from the direction it is facing) if it faces to the left it will read the top strand. 
OK, so how does polymerase know which way to sit down?  I really don't know the exact details of this, but polymerase is brought to the promoter of a gene by the pre-initiation complex, activators, and the whole group of proteins you didn't want to list in your question.  In addition to bringing polymerase to the right spot I think these proteins are also involved in pointing it in the right direction- but I don't know off the top of my head which ones actually do that job.
I hope that helped a bit and didn't just confuse you.
Colleen

[kalimna (OP)]

Hi Colleen,
Thanks for your answer - it has certainly clarified a few points. Particularly the role of the turtle-polymerase complex And it's the first time in about 5 years I have remembered the 3' - 5' directionality... I have vague memories of it in university lecturebs...

Would I be correct in thinking then, that as the promoters act for specific genes on one of the strands, my original question is null?
And as a follow up question - do you happen to know what sort of percentage of both complememntary strands each encode for a protein rather than being 'junk' DNA? Does that make sense?
Cheers,
Adam

[chris]

It's true that polymerase can only work in the 5' -> 3' direction, but that's not what governs which strand encodes a gene, otherwise only one strand would contain coding information. In fact both strands contain coding information, and in some cases the genes overlap with each other.

As an example, type 1 herpes simplex viruses (which are large double stranded DNA viruses) have a gene called LAT (which is actually a functional RNA), the end of which overlaps the end of another viral gene called ICP0, which is the linchpin in viral activity.

Some scientists think that turning on one of the genes helps to turn off the other (because they are anti-sense to each other and their two RNAs, being mirror-images, bind together and are degraded).

So the direction of gene expression, as suggested above, is down to promoters rather than polymerases. The promoter sequences recruits polymerase enzymes to the DNA template and dictates which parts are to be transcribed.


Chris

[WylieE]

Hi Adam,
  Ah yes, the old turtle-polymerase complex, sounds like a Dr. Suess story doesn’t it?  Sorry I didn't get it quite as clear as Chris did (and so succinctly- how does he do that?).  So I think your second question is what Chris is explaining about the overlap of genes.  I have a favorite example of that in plants.  This is from work done in the Zhu lab at UC Riverside. 
When a plant is in osmotic stress- such as during drought or salt stress they tend to accumulate compatible osmolytes to help protect cells from water loss and one of these is proline.  There is an enzyme that under normal circumstances breaks down proline, P5CDH, but during salt stress less of this enzyme is present and proline accumulates.  How P5CDH levels are turned down is pretty cool:
The end of the P5CDH gene overlaps with another gene on the opposite strand, SRO5.  SRO5 is induced by salt stress and so both SRO5 mRNA and P5CDH mRNA are produced.  Since they are complementary, they can bind and form double-stranded RNA which is degraded.  Since P5CDH mRNA is degraded less P5CDH enzyme is produced and since there is less P5CDH to break down proline, proline levels increase and help protect the plant form osmotic stress.
In their paper they suggest that there are thousands of convergent overlapping pairs in both animal and plant genomes and that this may be an important method of regulation.  If all this is true, I think it is a pretty clever system- it almost seems to act like a rheostat.
Still a bit wordy, but hey if I were able to answer as well as Dr. Chris I'd get paid the big bucks, right?
c-ya
Colleen

[chris]

Thanks Colleen, that's very complimentary of you. I also happen to think your example is better than mine because it applies to a eukaryotic system and is one I've not heard about, so thanks for educating me!

I think you dropped me a line this week about pain perception did you not?

Geoff Woods is coming along to the Naked Scientists programme on 4th February to talk about the research, including gender vulnerability to pain perception. His lab are currently looking into that precise question of whether some pain-prone people are higher expressors - we're waiting for the results with interest.

Chris

[Karen W.]

Greetings all,


Cheers,
Adam

HI Adam,

WELCOME !!..the above is the only part of your post that I understand !!  LOL []..but then I'm no academic here...just wanted to say ' Hello ' and hope you enjoy the site.

best Wishes

Neil

This was taken Directly from "A Brief history of Science" Consultant editor John Gribbin, (copyright, The ivy press limited 1998)

"Within the cell nucleus the DNA helix unzips as if to replicate itself, but instead it gathers RNA nucleotides to form a single strand of "messenger" RNA or mRNA. The mRNA strand detatches itself and carries its own version of the four-letter DNA message out of the nucleus into the surrounding cytoplasm, which contains free amnio acids. While the DNA helix zips itself together again, the mRNA message is used by cellular organelles called ribosomes to build the long chains of amnio acids that form proteins. Exactly how the four letter alphabets of DNA and mRNA are translated into  the twenty-letter amnio acid alphabet of proteins was a mystery to be solved after the structure of DNA itself. It was first worked out in 1960 by Marshall Nirenberg."


It sounds as if it uses itself to know which ones to use! Is that correct or am I misunderstanding?

[WylieE]

Thanks Dr. Chris,
 I did drop you a line on pain perception this week.  Cool!  I'm glad you'll have Dr. Woods on the show . . .I'll be waiting on pins and needles.
   I'm curious to see if there is an expression difference between men and women (that might explain a lot) and if that changes throughout our lifetime.

  The paper on the "nat-siRNA" in salt stress is Borsani et al.  Cell 123:1279.
In a talk he gave Dr. Zhu said that overlapping genes like this occur in 10% of the Arabidopsis genome and >20% of the human genome- if so, there might be many more examples of this in eukaryotes coming up soon. 
c-ya
Colleen

[chris]

Beyond just overlapping don't forget about nested genes, where one gene is hidden inside another one. The genes that make the acetyl choline nerve transmitter molecule and also transport it in vesicles to the nerve termini are nested within each other. The unc gene, which moves ACh into vesicles shares the 5' end of the ChAT gene and also extends into the first ChAT intron. This way both things, which need to be employed together get made together under the same control mechanisms, which is highly efficient.

Chris

[WylieE]

So complex and yet so elegant!  When I was a kid I dreamed of working for Bletchley Park, I was older than I should admit before I realized they probably weren't hiring anymore.  However, I have stumbled (tangentally) into this field and it is a cryptologist's dream and so universally applicable- from the smallest bacteria to the largest tree- when nature stumbles upon a good system of regulation that mechanism is preserved.   

[kalimna (OP)]

Greetings all.b
Wow - thanks for all the intresting replies. I now feel I know a little more about DNA transcription!
Karen - I actually have the Gribbin book you mention, and found it excellent indeed (though I must have forgotten that particular passage)
Chris - Again, very interesting regarding nested genes (esp ACh etc - as an anaesthetist, I have a little working interest of ACh) - I didnt realise they existed at all.

Fascinating stuff. Almost efficient enough in design to warrant an intelligent basis

Adam

[WylieE]

Hi Adam,
 I hope your moving went well and you didn't stimulate too many acetylcholine receptors in your lower back.   
I agree, very fascinating stuff.  I can see why at first glance someone might think there was a design.  However if someone was going to base and argument for intelligent design on efficiency, I'd have to point out RUBISCO.
c-ya
Colleen