3 Bases Thick

Quoted message said:

I think most textbooks are wrong when they say something like this text,

"(the genetic) code must be in the form of 3 bases - not one or two, because there are 20 different
amino acids used in protein synthesis, but there are only 4 different bases in mRNA." Solomon's
Organic Chem 6th ed.

This explanation is putting the cart before the horse. It is saying that because we have 20 AA now,
that must have been the aim of life on its first day then. That makes no sense. That's chemistry
that predicts the future!

I suggest that a codon is 3 bases because the first proto tRNA was three bases thick at the
anticodon. There is no way it could have been so small to code just 1 or 2 bases. It is the shape
and nothing more that determined that there were 3 bases in a codon.

Then what is important about 3 is that there is a center one. The center base IMO was most likely
to be an A or a U (due to thermal stability - less than GC more than non complimentary bases). A
coded for hydrophilic aa's U coded for hydrophobic aa's Then the code over time shifted to what we
have now (middle base most important, first base 2nd in importance 3rd base wobble.)

Comment? Also can anyone tell me the actual shape and width of an anti codon - 3 base section, on a
tRNA molecule.

I would recommend you download a free 'Chime' plugin for your browser, if it supports 'Chime', and
view the tRNA (chime) this way. This is probably the best way to examine the tRNA construction.
The tRNA is about 80 angstroms from anticodon to stem and the anticodon (position 34-35-36) is
about 8 angstrom in width. Position 33 is almost always an unmodified U that causes a very sharp
bend (the 'U-turn'😉 and presents the 3 base anti-codon to the mRNA codon inline. In the last few
years, there has been much better understanding of how the translation machinery (ribosome-tRNA)
functions but there is still much that is unclear. It should help in explaining the evolution of
the genetic code to first completely understand how the machine functions. I think you see the
many modified bases in tRNA as the primitive condition. I do not. I see these as later tweaks to
the translation machinery. I would like to see how tRNAs would be translated when modified bases
in the anti-codon loop (32-39) are not present (blocking the modifications). This should be the
early condition when the genetic code first evolved. Little yet has been done with these type of
experiments. William L Hunt

[snip]

. The tRNA is about 80 angstroms from anticodon to stem and the anticodon (position 34-35-36) is
about 8 angstrom in width. Position 33 is almost always an unmodified U that causes a very sharp
bend (the 'U-turn'😉 and presents the 3 base anti-codon to the mRNA codon inline. In the last few
years, there has been much better understanding of how the translation machinery (ribosome-tRNA)
functions but there is still much that is unclear. It should help in explaining the evolution of
the genetic code to first completely understand how the machine functions. I think you see the
many modified bases in tRNA as the primitive condition. I do not. I see these as later tweaks to
the translation machinery....

I see your point on this and could go either way. It is curious to me that there are this zoo of
bases on tRNA. If it was later - why isn't it more streamlined? It seems a lot to ask of a cell to
make up and assemble this zoo for every tRNA it needs.

One follow up. Inosine - primitive condition, or later tweaked base?

I would like to see how tRNAs would be translated when modified bases in the anti-codon loop (32-
39) are not present (blocking the modifications). This should be the early condition when the
genetic code first evolved. Little yet has been done with these type of experiments. William L Hunt

[snip]

On Wed, 10 Sep 2003 03:40:02 +0000 (UTC), [email hidden]

(TomHendricks474) said:

. The tRNA is about 80 angstroms from anticodon to stem and the anticodon (position 34-35-36) is
about 8 angstrom in width. Position 33 is almost always an unmodified U that causes a very sharp
bend (the 'U-turn'😉 and presents the 3 base anti-codon to the mRNA codon inline. In the last few
years, there has been much better understanding of how the translation machinery (ribosome-tRNA)
functions but there is still much that is unclear. It should help in explaining the evolution of
the genetic code to first completely understand how the machine functions. I think you see the
many modified bases in tRNA as the primitive condition. I do not. I see these as later tweaks to
the translation machinery....

I see your point on this and could go either way. It is curious to me that there are this zoo of
bases on tRNA. If it was later - why isn't it more streamlined? It seems a lot to ask of a cell to
make up and assemble this zoo for every tRNA it needs.

There are two types of modifications, those in the anticodon that improve translation and those 1/2
dozen plus elsewhere that provide additional h-bond linking that make the folded tRNA so rigid.
Whether this rigidity improves translation, I don't know but it may. In any case, it does improve
its resistance to degradation or, in your terminology, its thermal stability. The tRNAs are
endlessly reused and increasing their lifetime may be sufficient for selection of these internal
modifications. One or more genes are required to modify a standard base to a variant. Likewise, the
translation process is so important that slight tweaks (anticodon modifications) that improve the
translation have been selected even though it requires a host of genes to perform these
modifications after the tRNA has first been transcribed. Many of these modifications are in
position 34 (3rd codon pairing) but position 37 usually has long side chains added that reach over
to h-bond to the back of position 36 (1st codon pairing) and helping it in some way. It seems only
the middle position (35) needs no additional help.

Quoted message said:

One follow up. Inosine - primitive condition, or later tweaked base?

Remember when I say primitive condition I'm referring to the time/condition when the genetic code
evolved and not first life. I think you see these as being closer together in time than I do.
Inosine would be present as a monomer (IMP) but not part RNA strands at this later time when the
code evolved. Inosine use in the anticodon would be a later tweak. Even now tRNA is transcibed with
an A that is enzymatically changed to I. Also I is not used in mitochondria, chloroplasts or
archeabacteria. In eubacteria it is only used for translating one amino acid (Arginine). It is used
in eukaryotes to translate 8 amino acids.

[snip]