Central Dogma violated?

[*Hemidactylus*]

On his "Why Evolution is True" blog Jerry Coyne makes a curious comment
about exception to the Central Dogma about unidirectional information flow
from nucleic acid to protein. First he says:

https://whyevolutionistrue.wordpress.com/2017/08/18/aeon-tries-to-revive-lamarck-calling-for-a-paradigm-shift-in-evolution/

"The central dogma of molecular biology deals with the detailed
residue-by-residue transfer of sequential information. It states that such
information cannot be transferred back from protein to either protein or
nucleic acid."

Then later he says: "One exception to the central dogma is “epigenetic”
modification of DNA and the histone proteins used in packaging DNA. Some
environmental factors can act to modify the DNA, usually by attaching
methyl groups to its bases, and these modifications can not only change
gene action, but can be inherited—but only for a couple of generations."
[cue confused dogs tilting heads]

https://youtu.be/m2p1kMJwU7Q

Is this truly an exception to central dogma?

The Curmudgeon Waldorf has clearly delineated the Watson versus Crick
versions here:

http://sandwalk.blogspot.ca/2007/01/central-dogma-of-molecular-biology.html

Watson's goofy DNA to RNA to protein gets demolished by reverse
transcription. Crick's from Larry's post is:

"The Central Dogma. This states that once “information” has passed into
protein it cannot get out again."

More recently Larry flirts with Central Dogma abandonment issues while
considering prions and similar proteins effects on nucleic acids, but
asserts the strongest sense of Central Dogma being about impossibility of
reverse translation.

http://sandwalk.blogspot.com/2012/09/does-central-dogma-still-stand.html

So does the case Coyne presents above truly show exception to Central
Dogma? The brain clusters I had fine tuned to deal with this topic in late
90's have long since dissipated.

[RonO]

The central dogma hasn't been dogma for so long that it doesn't matter.
Reverse transcription has been a useful tool in molecular biology since
I was a graduate student, and it was known about before they
commercially purified it and made it available for common use. We are
talking around 40 years ago.

A better exception is prions. These are proteins that get their
structure altered due to some mishap. It happens spontaneously in cases
such as scrapie in sheep and Cruetzfeldt-Jakob disease in humans. The
thing is that after the structural alteration happens the prion can make
more of itself by altering the structure of normal proteins. So it can
be infective. Prion diseases like mad cow disease can be transferred
from the cow to humans by ingesting the beef that contains the prions.

There is also the example of RNA editing. RNA is transcribed from the
DNA, but nucleotides are added and they alter the coding sequence of the
RNA. This just means that the RNA sequence that originally comes from
the DNA does not code for the correct protein sequence until it is
edited after transcription. This editing can be very extensive. In
theory you could reverse transcribe the edited RNA and produce a new DNA
sequence with the final coding sequence that would not have to be
edited. I don't know if that ever gets done because the RNA editing
machinery seems to be some type of parasite in the genome that makes
itself required for the host to survive. It has become a normal
required life process for some organisms.

Ron Okimoto

[Don Cates]

While what you state below is all true, how does it affect the 'central
dogma' as stated in the above links?

> Reverse transcription has been a useful tool in molecular biology since
> I was a graduate student, and it was known about before they
> commercially purified it and made it available for common use.  We are
> talking around 40 years ago.
>
> A better exception is prions.  These are proteins that get their
> structure altered due to some mishap.  It happens spontaneously in cases
> such as scrapie in sheep and Cruetzfeldt-Jakob disease in humans.  The
> thing is that after the structural alteration happens the prion can make
> more of itself by altering the structure of normal proteins.  So it can
> be infective.  Prion diseases like mad cow disease can be transferred
> from the cow to humans by ingesting the beef that contains the prions.
>
> There is also the example of RNA editing.  RNA is transcribed from the
> DNA, but nucleotides are added and they alter the coding sequence of the
> RNA.  This just means that the RNA sequence that originally comes from
> the DNA does not code for the correct protein sequence until it is
> edited after transcription.  This editing can be very extensive.  In
> theory you could reverse transcribe the edited RNA and produce a new DNA
> sequence with the final coding sequence that would not have to be
> edited.  I don't know if that ever gets done because the RNA editing
> machinery seems to be some type of parasite in the genome that makes
> itself required for the host to survive.  It has become a normal
> required life process for some organisms.
>
> Ron Okimoto
>

--
--
Don Cates ("he's a cunning rascal" PN)

[*Hemidactylus*]

Which affects Watson's version. But what of Crick (1958)?

See
http://4.bp.blogspot.com/_DZH2cmCoois/Rau3h_-PdRI/AAAAAAAAAco/n4hixgjHU8M/s1600-h/Central_Dogma_Crick_1970_combined.jpg

And Larry's explanation: "These diagrams of potential information flow were
used by Crick (1958) to illustrate all possible transfers of information
(left) and those that are permitted (right)."

Or Crick restated in light of reverse transcription?

> and it was known about before they
> commercially purified it and made it available for common use.

They purified reverse transcription or reverse transcriptase?

> We are
> talking around 40 years ago.
>
> A better exception is prions. These are proteins that get their
> structure altered due to some mishap. It happens spontaneously in cases
> such as scrapie in sheep and Cruetzfeldt-Jakob disease in humans. The
> thing is that after the structural alteration happens the prion can make
> more of itself by altering the structure of normal proteins. So it can
> be infective. Prion diseases like mad cow disease can be transferred
> from the cow to humans by ingesting the beef that contains the prions.
>
> There is also the example of RNA editing. RNA is transcribed from the
> DNA, but nucleotides are added and they alter the coding sequence of the
> RNA. This just means that the RNA sequence that originally comes from
> the DNA does not code for the correct protein sequence until it is
> edited after transcription. This editing can be very extensive. In
> theory you could reverse transcribe the edited RNA and produce a new DNA
> sequence with the final coding sequence that would not have to be
> edited. I don't know if that ever gets done because the RNA editing
> machinery seems to be some type of parasite in the genome that makes
> itself required for the host to survive. It has become a normal
> required life process for some organisms.
>

But does reverse translation occur?


http://muppet.wikia.com/wiki/Statler_and_Waldorf?file=StatlerWaldorf.JPG

https://plus.google.com/photos/116237327501105508655/albums/profile/5627332472424784402

Uncanny resemblance?

[RonO]

Just the way that hemi was talking about it in his post. It isn't set
in stone and isn't inviolate. It still is the way things go most of the
time, but it isn't gospel.

Ron Okimoto

[RonO]

You need to provide figure legends. What do the dash lines mean?

We also know of RNA to RNA replication that does not go through a DNA
intermediate. So the diagrams don't much matter.

DNA to RNA to Protein has been considered to be the central dogma since
I've been involved with genetics, but we know that it isn't always the
way things work.

>
>> and it was known about before they
>> commercially purified it and made it available for common use.
>
> They purified reverse transcription or reverse transcriptase?

They knew about reverse transcriptase, but we didn't use it as a common
tool until it was purified and made commercially available.

[*Hemidactylus*]

Can tell explicitly from what Larry provided but I would throw the question
back to you about the lack of any arrows pointing from protein to RNA or
protein to DNA as a flow of sequence information. Impermissible. The dashed
lines are there though which makes me infer what's permitted though not
something known at the time? So reverse transcription and direct flow from
DNA to protein are permitted. I am unfamiliar with the latter.

I note curious absence of answer to my question below about reverse
translation. "... once (sequential) information has passed into protein it
cannot get out again (F.H.C. Crick, 1958)".

>
> We also know of RNA to RNA replication that does not go through a DNA
> intermediate. So the diagrams don't much matter.
>
> DNA to RNA to Protein has been considered to be the central dogma since
> I've been involved with genetics, but we know that it isn't always the
> way things work.
>

Larry calls that the Watson version.

Did Larry moonlight on Muppets?

[*Hemidactylus*]

Forget me. How does what Coyne says square with what Larry Moran has said
(the links).

[*Hemidactylus*]

Ugh! I too missed the subtlety, but look very closely. See the loops at DNA
and RNA that are missing with protein on the permissible diagram? RNA-RNA
replication permitted?

[RonO]

If the diagrams are from 1958 we hadn't even figured out that the code
was triplet. People were speculating about it, but it was a time when
they were trying to figure out how things like transcription and
translation worked.

My guess is that no one expected things to work in reverse (your protein
question). The Hershey-Chase experiment that was among the experiments
that led researchers to believe that DNA was the genetic material was
published before the structure of DNA. 1958 was half a decade after the
structure of DNA had been figured out. Before that people still
speculated that protein could be some type of genetic material, but they
were moving away from that scenario. Most researchers were
concentrating on how DNA stored the information and how it was
translated into proteins. Crick is credited with coming up with the
idea of RNA intermediates that were eventually called tRNAs (transfer
RNAs) that have the anticodon that pairs with the triplet code and has
an amino acid attached so that it can be added to an elongating peptide.
He speculated that the code could be three nucleotides because that is
all that would be needed to encode the known amino acids.

Ron Okimoto