Wobble - doesn't make sense



T

Tomhendricks474

Guest
Something doesn't ring true here -

"(Crick's) proposal, termed the wobble hypothesis suggested that whereas the steric requirement
between the anticodon of the tRNA and the codon of the mRNA may be very strict for the first two
positions, it may be more flexible at the third... allowing two codons that specify the same amino
acid and differ only at the third position to use the same tRNA in protein synthesis."

True as far as it goes but why is it so?

"(Gamov) reasoned that it would require at least 3 nucleotides for each amino acid to have its own
unique codon... Since there are 20 different amino acids that have to be specified, codons must
contain at least 3 successive nucleotides."

But that is backward reasoning. It seems to accept the fact that life demanded 20 aa's and 19 or 21
would not do. To me that is ridiculous reasoning. It's reasoning that fills in the facts to fit the
future goal - or what we think is the future goal. But codons were NOT building for the future.

Wobble only seems to make sense if you turn the argument around. I suggest this: Imagine a strand of
unpaired RNA bases sticking out from some paired bases. Its these 'naked' bases that would most
likely bond with other molecules. Example : note number = the most important positions of codon on
each end of a folded molecule

3 - 1 - 2- folded molecule - 2-1-3

a. I suggest there had to be at least 3 positions to have a center one. The center one was protected
by being in the center with at least a base on either side and at least it is sticking 2 bases
outside of the fold so it is accesible. Thus the center one should be the most important in
coding = #1

b. To expand coding another positons was included. It was the position nearest the folded molecule.
Or rather I would call it the 2nd most protected and at the same time the most easily accessible
base position = #2

c. More coding is needed and in this case all that is necessary in the #3 position - or the out on a
limb position - is fit of the 3rd position base. Thus it is in almost every case either an A/G
purine OR a C/U pyrimidine

Also base stacking plays an important part with it favoring middle for most stability then the other
two in the same order as above.

The wobble IMO is not to fit someone's preconceived notion of how many aa's we need. It is there as
the last step in expanding an h-bonding code of 3 positions - at the least protected and most
vulnerable spot. And that vulnerability of being the position way out on a limb, and the fact that
it is not needed to code other than as a purine or pyrimidine, and it's lesser base stacking; is why
it wobbles

Now look at a tRNA and you see these 2 naked ends clear as day. The acceptor stem from the molecule
out is molecule - discriminator base 73 - C - C - A to adapt to aa

The anti codon from the 3' - 5' end molecule - purine base 37 - [anticodon 36 - 35 - wobble} then
imagine a cut to make this end a single strand instead of a loop.

Both ends are evolved versions of the same thing

Comment?
 
T

Tomhendricks474

Guest
<< . I suggest there had to be at least 3 positions to have a center one. The center one was
protected by being in the center with at least a base on either side and at least it is sticking 2
bases outside of the fold so it is accesible. >>

Perhaps too the center one would hold with h-bonds under certain conditions, if it was protected on
both sides with other bases, and had base stacking etc. Perhaps the key number of 3 base pairs has
to do with what was necessary to have this h- bond with any other molecule

If this is so then it suggests the first connection between RNA and Amino acids. If they could
bond together they would be less likely to be denatured in the high heat of this early period on
hot Earth.
 
L

Larry Moran

Guest
On Sat, 21 Feb 2004 06:31:00 +0000 (UTC),
TomHendricks474 <[email protected]> wrote:

>Someone else wrote:
>> I suggest there had to be at least 3 positions to have a center one. The center one was protected
>> by being in the center with at least a base on either side and at least it is sticking 2 bases
>> outside of the fold so it is accesible. >>
>
> Perhaps too the center one would hold with h-bonds under certain conditions, if it was protected
> on both sides with other bases, and had base stacking etc.

The interaction between two trinucleotides (3 "bases") is governed almost entirely by stacking
interactions. The hydrogen bonds play an insignificant role in the overall stability of the double-
stranded molecule. The hydrogen bonds are necessary for complementarity but that's a different
matter altogether.

You need to have three nucleotides in order to have stacking interactions.

> Perhaps the key number of 3 base pairs has to do with what was necessary to have this h- bond with
> any other molecule

No, you need three nucleotides in order to get stacking interactions that make the formation of double-
stranded molecules thermodynamically favorable.

> If this is so then it suggests the first connection between RNA and Amino acids. If they could
> bond together they would be less likely to be denatured in the high heat of this early period on
> hot Earth.

The melting point of a double-stranded trinucleotide is probably less than room temperature.

Larry Moran
 
I

Irr

Guest
> "(Gamov) reasoned that it would require at least 3 nucleotides for each
amino
> acid to have its own unique codon... Since there are 20 different amino acids that have to be
> specified, codons must contain at least 3 successive nucleotides."
>
> But that is backward reasoning. It seems to accept the fact that life demanded 20 aa's and 19
> or 21 would not do. To me that is ridiculous reasoning. It's reasoning that fills in the facts
> to fit the
future
> goal - or what we think is the future goal. But codons were NOT building
for
> the future.

The ideas of Gamow, Crick, and others were not concerned about evolution, but rather how DNA->RNA-
>protein coding took place. They were arguing based on known data, namely the 4 base composition of
DNA and the known 20 amino acids that biochemistry was built on. No teleology required.
 
T

TomHendricks474

Guest
<< The ideas of Gamow, Crick, and others were not concerned about evolution, but rather how DNA->RNA-
>protein coding took place. They were arguing based on known data, namely the 4 base composition of
DNA and the known 20 amino acids that biochemistry was built on. No teleology required. >>

Agreed. But in talking about the origin, we've got to look at wobble in a new way and re-examine it
-not as a means to getting to an end, but as a way that some chemical variants were able to survive
that day's heat cycle, while others could not.