Re: pure chance

billgr@cco.caltech.edu
Mon, 13 Jan 1997 17:14:30 -0800 (PST)

Gene,

> According to billgr@cco.caltech.edu:
>
> > I think the disagreement we are having is about what the reverse
> > transcription is. There is no doubt that the proteing information
> > can't be 'put back into' the DNA, because information is lost in
> > the decoding. This is uncontroversial, but I do *not* think that
> > this means that reverse transcription is *impossible*. (Or even
> > that it doesn't happen.)
>
> A nitpicky note: Reverse transcription occurs when the enzyme "reverse
> transcriptase" transcribes RNA into DNA. Translation occurs when the
> spliced mRNA is translated into the protein. Reverse translation which,
> as far as I know, has never been seen to occur, would seem to describe
> the making of an RNA strand from a protein. In eucaryotic cells the
> mRNA would then have to be "unspliced" somehow with the control elements
> placed *back* into the strand and then reverse transcription would have
> to occur for it to be put back into usable DNA. I don't know your
> bounds on "impossible" but that's pretty darn close in my book! :-)

Oops! I thought I was being careful to only say 'reverse translation'
but obviously I wasn't... Thanks for looking over my shoulder.

> Information loss for eucaryotic cells (for all I know about it) seems
> to not occur until the mRNA is generated. At this point the introns
> are removed and the 5' and 3' regions which govern the RNA polymerase
> action are cut off. How you could possibly reconstruct them is not known
> to me. I would say the lesser information loss occurs at mRNA
> translation to protein. You could, in theory, duplicate the codons since
> you have a limited number of selections. How you would replace the
> control regions and introns is harder. Codon usage is specific for
> individual creatures and the wrong codon choice could doom your coded
> protein in certain instances. I work on Entamoeba histolytica and it
> has never yet been seen to use 4 codons and another 6 are quite rare.
> E. histolytica is a very AT rich organsim. Certain thermophilic organisms
> are very GC rich.

Now you're going a bit fast. What are the 5' and 3' regions?
And I'm not following the possible reconstructability of the codons
from mRNA to protein. Has the 61 letters ---> 20 amino acid thing
been broken by this time? (Maybe that's what the 5' and 3' regions
have to do with?) The AT-rich vs. GC-richness is interesting. Does
anyone know why that is the case?

> > if reverse transcription is accompanied by a random process which selects
> > codons within the space of possible sequences to code for a protein, then
> > all the information in the original DNA sequence can appear in the
> > reverse translated one.)
>
> As I mentioned above, in certain instances, certain codon choices might
> spell doom if you ever wanted a functional protein to be made again. They
> aren't sure why this is, as far as I know (not far) but too many Gs and Cs
> in Entamoeba are thought to gum up the RNA polymerase machinery if they
> occur in certain spots, so the RNA strand prior to mRNA doesn't get made.
> Certain codons in certain organisms might also harm the ability of the
> mRNA to be made from the splicing machinery. And lots of As and Ts in
> thermophilic organisms would result in the DNA being denatured (AT-rich
> regions melt more readily than GC rich regions since ATs are held together
> by two hydrogen bonds while GC pairs have three) at the temperatures at
> which they exist.

Fascinating. So there are 'higher-level' constraints on relative
abundances on the bases?

-Greg